Cytokine Signalling Forum

Publications





April 21

Risk of venous thromboembolism associated with tofacitinib in patients with rheumatoid arthritis: a population-based cohort study

Desai RJ, Pawar A, Khosrow-Khavar F, Weinblatt ME, Kim SC.
Rheumatology (Oxford). 2021 Mar 22:keab294. Epub ahead of print. DOI: 10.1093/rheumatology/keab294

A population-based cohort study of 87,653 RA patients has found no evidence for an increased risk of venous thromboembolism (VTE) for tofacitinib, versus TNFis, in patients with RA. The introduction of JAKinibs, almost a decade ago, has provided an important oral option for the treatment of RA. However, in recent years, a safety concern, relating to incidence of VTE after treatment, has emerged. Consequently, both the US and European regulatory authorities now recommend caution for use of tofaci...

Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects

Estupiñán HY, Berglöf A, Zain R, Smith CIE.
Front. Cell Dev. Biol. 9:630942 DOI: 10.3389/fcell.2021.630942

Understanding of the B-cell receptor signalling pathway led to the identification of a suitable drug target to addresses autoimmunity and inflammation in areas such as MS, RA, pemphigus and SLE. There are currently 22 BTKis in various stages of clinical development. However, AEs such as cardiovascular and bleeding side effects, as well as rash, diarrhoea and infections have been associated with the inhibition of other kinases with a BTKi-binding cysteine in their catalytic domain. Based on clini...

JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib

Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA.
Ann Rheum Dis. 2021 Mar 19:annrheumdis-2020-219012. Epub ahead of print. DOI: 10.1136/annrheumdis-2020-219012

The first study to combine in vitro inhibition of cytokine responses in whole blood with clinical pharmacokinetics of individual JAKinibs to model daily cytokine-mediated pharmacodynamic profiles in healthy individuals and patients with RA, has demonstrated that JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type. Traves and colleagues have observed that JAKinibs have unique, differential effects on specific cytokine signalling pathways, dependent on cytokine stimulus, S...

Filgotinib, a Novel JAK1-Preferential Inhibitor for the Treatment of Rheumatoid Arthritis: An Overview from Clinical Trials

Tanaka Y, Kavanaugh A, Wicklund J, McInnes IB.
Mod Rheumatol. 2021 Mar 19:1-26. Epub ahead of print. DOI 10.1080/14397595.2021.1902617

Filgotinib is the latest JAKinib to enter the international market for the treatment of RA, receiving regulatory approval in Japan and Europe late last year. In this review paper, Tanaka Y et al. examine the clinical evidence supporting its use as a later-line treatment, in accordance with international RA management guidelines, and provide their expert opinions on JAKinibs from a clinical perspective. The core clinical programme evaluating filgotinib in patients with moderately-to-severely acti...

March 21

Upadacitinib en Artritis Reumatoide: Una Evaluación de Riesgo-Beneficio en el Programa de Fase III

Conaghan PG, Mysler E, Tanaka Y, Da Silva-Tillmann B, Shaw T, Liu J, Ferguson R, Enejosa JV, Cohen S, Nash P, Rigby W, Burmester G.
Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-w

Upadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme. In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integra...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Efectos de Un Año de Terapia con Tofacitinib en el Metabolismo Óseo en Artritis Reumatoide

Hamar A, Szekanecz Z, Pusztai A, Czókolyová M, Végh E, Pethő Z, Bodnár N, Gulyás K, Horváth Á, Soós B, Bodoki L, Bhattoa H P, Nagy G, Tajti G, Panyi G, Szekanecz É, Domján A, Hodosi K, Szántó S, Szűcs G, Szamosi S.
Osteoporos Int 2021 Feb 9 DOI 10.1007/s00198-021-05871-0

Thought to be the first study of its kind, Hamar, et al. have demonstrated the effect of one-year tofacitinib treatment on bone mineral density (BMD) in RA patients. While the association between RA and osteoporosis is well known, and evidence indicates that up to 70% of these patients have reduced BMD, little information is available on how the JAK inhibitor tofacitinib affects bone status, areal and volumetric BMD, and bone turnover markers. In this prospective study, 30 patients were asse...

Seguridad y Eficacia de Filgotinib: Resultados de Hasta 4 Años de un Estudio de Extensión Abierto de los Programas de Fase 2 en Artritis Reumatoide

Kavanaugh A, Westhovens RR, Winthrop KL, Lee SJ, Tan Y, An D, Ye L, Sundy JS, Besuyen R, Meuleners L, Stanislavchuk M, Spindler AJ, Greenwald M, Alten R, Genovese MC.
J Rheumatol. 2021 Feb 1:jrheum.201183. DOI: 10.3899/jrheum.201183.

A long-term extension study of filgotinib showed consistent safety profile and sustained efficacy with the drug for up to four years. The DARWIN 3 study, for patients who previously completed either the 24-week DARWIN 1 study (filgotinib + MTX) or the DARWIN 2 study (filgotinib monotherapy), enrolled 739 patients with RA. At the time of analysis, 440 patients had received four years or more of filgotinib. Exposure-adjusted incidence rate per 100 patient-years-of-exposure for TEAEs was 24.6 i...

Keywords: JAK, Filgotinib, Clinical, Phase 2

Estudio de Seguridad Comparativa Pos-Aprobación de Tofacitinib y Fármacos Biológicos Antirreumáticos Modificadores de la Enfermedad: Resultados de 5 años de un Registro de Artritis Reumatoide basado en los Estados Unidos

Kremer JM, Bingham CO 3rd, Cappelli LC, Greenberg JD, Madsen AM, Geier J, Rivas JL, Onofrei AM, Barr CJ, Pappas DA, Litman HJ, Dandreo KJ, Shapiro AB, Connell CA, Kavanaugh A.
ACR Open Rheumatol. 2021 Feb 11.

Analysis from the US Corrona RA registry has provided the longest-term real-world safety data for a JAK inhibitor to date. The analysis showed that the cohorts had similar adverse events, except for higher herpes zoster rates for tofacitinib initiators vs bDMARDs. Kremer JM, et al. analysed adult patients with RA newly initiating tofacitinib, or a bDMARD, to compare incidence rates of MACE, SIEs, HZ, malignancies and death. VTE data were also collected prospectively and assessed descriptively t...

Keywords: JAK, Tofacitinib, Clinical

¿Cuál Resultado Reportado por el Paciente es el más Importante para los Pacientes Reumatológicos para se Rastrear Digitalmente? Un Estudio Longitudinal de Mundo- Real de ArthritisPower

Nowell WB, Gavigan K, Kannowski CL, Cai Z, Hunter T, Venkatachalam S, Birt J, Workman J, Curtis JR.
Arthritis Res Ther. 2021;23(1):53.

Fatigue, physical function, pain, and morning joint stiffness are the most important PROs to track, according to the rheumatology patients who experience these symptoms. Increasingly used, alongside clinical measures, to track symptoms and assess disease activity over time, patient-reported outcomes (PROs) are also important indicators of quality of life and treatment effectiveness. To enable us to better understand which PROs patients with rheumatic and musculoskeletal disease consider most im...

Keywords: JAK, Real World, PRO

February 21

Filgotinib en Combinación con Metotrexato o Monoterapia Versus Metotrexato Monoterapia en Pacientes con Artritis Reumatoide Activa con Exposición Limitada o nula a Metotrexato: El Estudio de Fase 3, Aleatorizado Controlado FINCH 3

Westhovens R, Rigby WF, van der Heijde D, Ching DW, Stohl W, Kay J, Chopra A, Bartok B, Matzkies F, Yin Z, Guo Y, Tasset C, Sundy JS, Jahreis A, Mozaffarian N, Messina OD, Landewé R BM, Atsumi T, Burmester GR.
Ann Rheum Dis. 2021 Jan 15:annrheumdis-2020-219213.

Filgotinib doses in combination with MTX have shown improved signs, symptoms and physical function in patients with RA and limited or no prior MTX exposure. FIL 200mg monotherapy did not have a superior ACR20 response rate versus MTX. This 52-week, phase 3 study evaluated FIL in 1252 patients with RA. Patients were randomised to FIL 200mg + MTX or FIL 100mg + MTX, FIL 200 mg monotherapy, or MTX monotherapy. The primary endpoint was the proportion patients achieving ACR20 at week 24. Safety was...

Keywords: JAK, Filgotinib, Clinical, Phase 3

Upadacitinib Monoterapia Versus Metotrexato Monoterapia en Pacientes Japoneses con Artritis Reumatoide Metotrexato Naïve: Un subanálisis del estudio de fase 3 SELECT-EARLY

Takeuchi T, Rischmueller M, Blanco R, Xavier RM, Ueki Y, Atsumi T, Chen S, Friedman A, Pangan AL, Strand V, van Vollenhoven RF.
Mod Rheumatol 2021;26:1–16.

In this sub-analysis of the Phase 3 SELECT-EARLY study, UPA demonstrated clinical efficacy superior to placebo in the Japanese subpopulation. Along with a favourable efficacy observed with the Japan-specific 7.5 mg dose of UPA for all secondary endpoints. SELECT-EARLY was designed to study the safety and efficacy of UPA 15 and 30mg as monotherapy, but it also included a subset of 138 Japanese patients, 40% of whom were randomised to receive UPA 7.5mg. This was designed to meet the requirements...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Señalización JAK/STAT Inducida por Citoquinas está Asociada con Artritis Reumatoide y Actividad de la Enfermedad

Ptacek J, Hawtin RE, Sun D, Louie B, Evensen E, Mittleman BB, Cesano A, Cavet G, Bingham CO III, Cofield SS, Curtis JR, Danila MI, Raman C, Furie RA, Genovese MC, et al.
PLoS ONE 2021;16(1):e0244187

This analysis provides evidence that immune cell signalling pathways are important in RA. There were consistent differences between RA patients and healthy controls in IFNα, IL-6, IL-10 and GM-CSF+ IL-2 induced JAK/STAT signalling in multiple immune cell subsets. We know that RA is characterised by dysregulation of immune responses, but the exact cause is unknown. Recently, single-cell transcriptomics and mass cytometry confirmed the critical role of activated immune cells and fibroblasts...

Keywords: JAK, MOA

Filgotinib Versus Placebo o Adalimumab en Pacientes con Artritis Reumatoide y Respuesta Inadecuada a Metotrexato: Un Ensayo Clínico Aleatorizado de Fase III

Combe B, Kivitz A, Tanaka Y, van der Heijde D, Simon JA, Baraf HSB, Kumar U, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy JS, Jahreis A, Genovese MC, Mozaffarian M, Landewé RBM, Bae S-C, Keystone EC, Nash P.
Ann Rheum Dis. 2021 Jan 27:annrheumdis-2020-219214

Filgotinib improved RA signs and symptoms, physical function, and inhibited radiographic progression. FIL 200mg plus MTX, but not FIL 100mg plus MTX showed non-inferiority to ADA plus MTX, based on DAS28(CRP) low disease activity. FIL was also well tolerated in RA patients with inadequate response to MTX. This 52-week, phase 3 randomised clinical trial (FINCH 1) evaluated the efficacy and safety of FIL in patients with RA randomised to FIL 200 or 100mg, ADA 40mg, or placebo, all with background...

Keywords: JAK, Filgotinib, Clinical, Efficacy

January 21

Poster: JAKi Recommendations for Use

Nash P, et al.
Ann Rheum Dis 2021;80:71–87.

Points to Consider for the Treatment of Immune-Mediated Inflammatory Diseases With Janus Kinase Inhibitors: A Consensus Statement. The poster highlights all the key considerations from the consensus statement. Download by Clicking on the Links Above

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

Mease PJ, Lertratanakul A, Anderson JK, Papp K, Van den Bosch F, Tsuji S, Dokoupilova E, Keiserman M, Wang X, Zhong S, McCaskill RM, Zueger P, Pangan AL, Tillett W.
Annals of the rheumatic diseases. 2021 Mar 1;80(3):312-20.

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA. Despite the availability of bDMARDs in PsA, only a small proportion of patients achieve the recommended target of minimal disease activity; as such, additional treatment options are needed. Upadacitinib is under evaluation for PsA. This paper reports the 24-week data...

Tofacitinib in psoriatic arthritis patients: skin signs and symptoms and health-related quality of life from two randomized Phase 3 studies

Merola JF, Papp KA, Nash P, Gratacós J, Boehncke W-H, Thaçi D, Graham D, Hsu M-A, Wang C, Wu J, Young P.
J Eur Acad Dermatol Venereol 2020;34:2809–2820.

Considering the multi-domain nature of PsA, effective treatments must demonstrate efficacy across a range of clinical and patient-reported outcomes. Dermatologic symptoms often precede rheumatic manifestations in people with PsA, typically by 10 years. Tofacitinib demonstrated significant improvements across a range of outcomes including burdensome dermatologic symptoms. This post hoc analysis included data from two double-blind, Phase 3 studies in patients with active PsA and an inadequate res...

EULAR Definition of Difficult-to-Treat Rheumatoid Arthritis

Nagy G, Roodenrijs NMT, Welsing PMJ, Kedves M, Hamar A, van der Goes MC, Kent A, Bakkers M, et al.
Ann Rheum Dis 2021;80:31–35.

A significant proportion of people with RA remain symptomatic despite treatment according to current management recommendations. Different terms have traditionally been used to describe this subpopulation, including severe, refractory, resistant to multiple drugs or treatments, established and difficult-to-treat. A recent survey indicated that – in addition to new drugs – new management approaches are needed for optimal treatment in these patients. A EULAR Task Force agreed the unifo...

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study

Pappas DA, St John G, Etzel CJ, Fiore S, Blachley T, Kimura T, Punekar R, Emeanuru K, Choi J, Boklage S, Kremer JM.
Ann Rheum Dis 2021;80:96–102.

RA treatment guidelines recommend a treat-to-target approach guided by disease stage and treatment history, yet the optimal sequence of different treatment modalities has not been established. Data from Corrona – were used to evaluate the comparative effectiveness of TNFi versus non-TNFi bDMARDs and tsDMARDs as first-line treatment following csDMARD failure. Results support RA guidelines recommending individualised care based on clinical judgement and consideration of patient preference. T...

Points to Consider for the Treatment of Immune-Mediated Inflammatory Diseases With Janus Kinase Inhibitors: A Consensus Statement

Nash P, Kerschbaumer A, Dorner T, Dougados M, Fleischmann RM, Geissler K, McInnes I, Pope JE, van der Heijde D, Stoffer-Marx M, Takeuchi T, Trauner M, Winthrop KL, de Wit M, Aletaha D, Baraliakos X, Boehncke W-H, Emery P, Isaacs JD, Kremer J, Lee EB, et al.
2021 Jan;80(1):71-87. doi: 10.1136/annrheumdis-2020-218398. Epub 2020 Nov 6.

JAKi are approved in various immune-mediated inflammatory diseases. With five JAKi now licensed, this paper reviews key points to consider in their use to assist clinicians, patients, and other stakeholders once the decision is made to commence JAKi. The consensus was developed by a Steering Committee and an expanded Task Force using EULAR standard operating procedures. The committee included patients as well as experts in rheumatology, gastroenterology, haematology, dermatology, and infectious ...

December 20

Eficacia de Baricitinib en pacientes con artritis reumatoide moderada a severa con 3 años de tratamiento: resultados del estudio a largo plazo

Smolen JS, Xie L, Jia B, Taylor PC, Burmester G, Tanaka Y, Elias A, Cardoso A, Ortmann R, Walls C, Dougados M.
Rheumatology 2020; doi:10.1093/rheumatology/keaa576

Three year follow up data for baricitinib demonstrated efficacy in populations that span the clinical disease continuum in RA, including DMARD-naïve, MTX-IR, csDMARD-IR, and bDMARD-IR and was well tolerated. This study evaluated achievement and maintenance of LDA, remission and physical functioning in patients treated with baricitinib for up to 3 years. Data were analysed from two 52-week, Phase 3 studies (RA-BEAM and RA-BEGIN), and one ongoing long-term extension (RA-BEYOND). Patients com...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Puntos importantes en el tratamiento de enfermedades inflamatorias inmunomediadas con inhibidores de Janus Quinasa: una revisión sistemática de la literatura

Kerschbaumer A, Smolen JS, Nash P, Doerner T, Dougados M, Fleischmann R, Geissler K, McInnes IM, Takeuchi T, Trauner M, Winthrop K, de Wit M, Boehncke W-H, Falzon L, van der Heijde D.
RMD Open 2020;6:e001374 doi:10.1136/rmdopen-2020-001374

Trials of JAKi have been conducted in many therapy areas, including rheumatology, dermatology and gastroenterology. In 2019, a task force was set up to create a consensus to guide clinicians on how to use JAKi in clinical practice. This systematic literature review conducted in 2019 support this consensus In line with EULAR’s standardised operating procedures for recommendations, a literature search was conducted in EMBASE, Medline and the Cochrane Library databases. To evaluate the effica...

Cambiando entre el inhibidor de Janus quinasa upadacitinib y adalimumab siguiendo respuesta insuficiente: eficacia y seguridad en pacientes con artritis reumatoide

Fleischmann RM, Blanco R, Hall S, Thomson GTD, Van den Bosch FE, Zerbini C, Bessette L, Enejosa J, Li Y, Song Y, DeMasi R, Song I-H.
Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-21841220

Both ACR and EULAR recommend adding a biologic or targeted synthetic DMARD in patients who do not achieve treatment goals at follow-up. Findings indicated that an immediate switch in mechanism of action (from JAKi to TNFi and vice versa) following treat-to-target principles is feasible with minimal risk of flare regardless of whether patients are switched due to non-response or incomplete-response. SELECT-COMPARE followed treat-to-target principles to examine the efficacy of switching in two pat...

November 20

Perfil de Seguridad de Upadacitinib en Artritis Reumatoide: Un análisis integrado de seguridad del Programa Clínico de Fase III SELECT

Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR.
Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510

This integrated Phase III safety analysis of UPA showed that UPA had a similar profile to ADA and MTX for serious infections, malignancies, and thromboembolic events. Patients receiving UPA had increased risk of HZ and creatine phosphokinase elevation versus ADA. This integrated Phase III safety analysis of UPA examined >3500 RA patients and 4000 patient-years of exposure. Data were pooled from 3834 patients in SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY s...

Keywords: JAK, Upadacitinib, Clinical, Safety

Translated by: Igor Kos

Ensayo Clínico de Upadacitinib o Abatacept en Artritis Reumatoide

Rubbert‑Roth A, Enejosa J, Pangan AL, Haraoui B, Rischmueller M, Khan N, Zhang Y, Martin N, Xavier RM.
N Engl J Med 2020;383:1511–21 DOI: 10.1056/NEJMoa2008250

In patients with refractory RA to bDMARDs, upadacitinib was found to be superior to abatacept in DAS28-CRP change from baseline and the achievement of remission at week 12. 612 bDMARD-IR patients were randomised 1:1 to UPA 15 mg QD or ABA, each in combination with stable synthetic DMARDs. At Week 12, patients with <20% decrease in TJC and Swollen joint count (SJC) had background medication adjusted or added. All patients completing Week 24 were eligible to remain in an open-label, long-term ...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

Translated by: Igor Kos

Incidencia Basada en Edad (<65 vs ≥65 años) de Infecciones y Infecciones Graves con Tofacitinib versus DMARDs Biológicos en los Ensayos Clínicos en Artritis Reumatoide en los EE.UU. y en el Registro Corrona RA

Winthrop KL, Citera G, Gold D, Henrohn D, Connell CA, Shapiro AB, Shi H, Onofrei AM, Pappas DA, Schulze-Koops H.
Ann Rheum Dis 2020; DOI: 10.1136/annrheumdis-2020-218992

Reports from clinical trials and the US Corrona RA registry showed that serious infection event (SIE) incidence was higher in older versus younger patients with RA receiving 10 mg BID of TOF and ADA, however, SIE risk was similar between age groups with TOF 5 mg BID and ADA. Data were collected from Phase II–IV tofacitinib studies, and the US Corrona RA registry. The clinical data set evaluated patients receiving TOF 5 and 10 mg BID versus TNFi (ADA/ETN) in RA patients aged ≥50 years. ...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

October 20

Caracterización Preclínica de Itacitinib (INCB039110), un Nuevo Inhibidor Selectivo de JAK1, para el Tratamiento de Enfermedades Inflamatorias

Covington M, He X, Scuron M, Li J, Collins R, Juvekar A, Shin N, Favata M, Gallagher K, Sarah S, Xue CB, Peel M, Burke K, Oliver J, Fay B, Yao W, Huang T, Scherle P, Diamond S, Newton R, Zhang Y, Smith.
European Journal of Pharmacology. 2020 Oct 15;885:173505. doi: 10.1016/j.ejphar.2020.173505

Itacitinib is an orally active JAK inhibitor and effectively delayed disease onset, reduced symptom severity, and accelerated recovery of inflammatory diseases in mouse models. Covington M et al demonstrated itacitinib’s high selectivity for JAK 1, its inhibition on IL-2 induced T cell proliferation and JAK/STAT signalling, its ability to also inhibit of the JAK/STAT pathway in response to IL-6 stimulation, and its effect on rat adjuvant induced arthritis model. The study used recombina...

Keywords: JAK, Preclinical, Selectivity

Translated by: Igor Kos

Eficacia de Baricitinib en el Tratamiento de la Artritis Reumatoide: Efecto Modulatorio en Biomarcadores Inflamatorios y de Fibrose en un Escenario de Vida Real

Alessandro M, Perillo F, Refini R, Bergantini L, Bellisai F, Selvi E, Cameli P, Manganelli S, Conticini E, Cantarini L, Sestini P, Frediani B, Bargagli E.
Int Immunopharmacol. 2020 Sep;86:106748.

BARI demonstrated to be a safe immune modulator that reduces the concentrations biomarkers of lung fibrosis and inflammation in RA patients, including a subgroup with interstitial lung involvement. Professor Alessandro and colleagues analysed the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment. Fifteen patients were recru...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

Baricitinib, un Fármaco con Efecto Potencial en la Prevención de la Entrada del SARS-COV-2 en las Células Blanco y en el Control del “Cytokine-Storm” Inducido por COVID-19

Zhang X, Zhang Y, Qiao W, Zhang J, Qi Z.
Journal of International Immunopharmacology. 2020 Sep;86:106749. doi: 10.1016/j.intimp.2020.106749.

BARI may potentially interrupt the passage of SARS-CoV-2 into the target cells by binding to AAK1 and GAK, which are regulators of the ACE2 receptor regulator identified for its uptake, and could also treat cytokine storm through suppression JAK1/JAK2. Professor Zhang and et al reviewed BARI, as a potential drug to prevent SARS-COV-2 from entering target cells. They also evaluated BARI’s ability to control COVID-19 induced cytokine storm. As a cell surface protein, ACE2 is involved in re...

Keywords: JAK, Baricitinib

Translated by: Igor Kos

Tofacitinib y Baricitinib son Capturados por Diferentes Mecanismos de Captura Determinando la Eficacia de Ambos los Fármacos en AR

Amrhein J, Drynda S, Schlatt L, Karst U, Lohmann C, Ciarimboli G, Bertrand J.
Int. J. Mol. Sci. 2020; 21:6632 DOI: 10.3390/ijms21186632

Amrhein et al examined the different uptake and expulsion mechanisms of BARI and TOF in cellular assays. Different cellular uptake mechanism for BARI and TOF was observed and showed that BARI’s transport was not dependent on organic cation transporters. Results indicated TOF was exported from RASF in a MATE-1 dependent way. TOF might be exported from healthy cells, thereby not inhibiting JAK pathway in these cells The interaction of BARI and TOF with OCTs was investigated using quenching ...

Keywords: JAK, Tofacitinib, Preclinical, MOA

Translated by: Igor Kos

September 20

Incidencia de Eventos Tromboembólicos Arteriales y Venosos Reportados en Los Programas de Desarrollo de Tofacitinib en Artritis Reumatoide, Psoriasis y Artritis Psoriásica y de Datos de Mundo Real

Mease P, Charles-Schoeman C, Cohen S, Fallon L, Woolcott J, Yun H, Kremer J, Greenberg J, Malley W, Onofrei A, Kanik KS, Graham D, Wang C, Connell C, Valdez H, Hauben M, Hung E, Madsen A, Jones TV, Curtis JR.
Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.

Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...

Keywords: JAK, Tofacitinib, Cardiovascular

Translated by: Igor Koz

Evaluación de la Asociación de los Anticuerpos anti-CarbV y anti- MCV en el baseline con la respuesta al tratamiento y con la progresión radiográfica en una población con AR tratada con Metotrexato o Baricitinib: un análisis post-hoc de RA-BEGIN

López-Romero P, Martinez-Gamboa L, Bang H, de la Torre I, Holzkämper T, Feist E.
Arthritis Res Ther. 2020;22(1):193

Autoantibodies associated with the onset of RA have gained attention in recent years as prognostic biomarkers. Though not used diagnostically, anti-CarbV (carbamylated vimentin) and anti-MCV (vimentin modified by citrullination) baseline titers are being investigated as predictors of treatment response. In this post-hoc analysis of data from the RA-BEGIN cohort of active RA patients, López-Romero and colleagues consider the potential predictive values of baseline anti-CarbV and anti-MCV t...

Keywords: JAK, Baricitinib, Clinical, Radiographic

Translated by: Igor Koz

Infecciones en los Ensayos Clínicos de Baricitinib en Pacientes con Artritis Reumatoide Activa

Winthrop KL, Harigai M, Genovese MC, Lindsey S, Takeuchi T, Fleischmann R, Bradley JD, Byers NL, Hyslop DL, Issa M, Nishikawa A, Rooney TP, Witt S, Dickson CL, Smolen JS, Dougados M.
Annals of the Rheumatic Diseases, May 2020

Baricitinib, an oral selective JAK1 and JAK2 inhibitor,8 demonstrated significant clinical efficacy in phase 3 RA trials. Pooled data from these trials, including a long-term extension (LTE), inform the safety profile for baricitinib, mainly to evaluate the incidence of infection in patients with active rheumatoid arthritis (RA), with a focus on serious infection, tuberculosis (TB), herpes zoster (HZ) and opportunistic infection (OI). The data collected were from eight double-blind randomised ...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor Koz

Tasas de Incidencia de Eventos de Enfermedad Intersticial Pulmonar en Pacientes con Artritis Reumatoide Tratados con Tofacitinib

Citera G, Mysler E, Madariaga H, Cardiel M H, Castaneda O, Fischer A, Richette P, Chartrand S, Park J K, Strengholt S, Rivas J L, Thorat A V, Girard T, Kwok K, Wang L.
Journal of Clinical Rheumatology, Aug 2020 doi: 10.1097/RHU.0000000000001552.

This study highlights the importance of accounting for known risk factors of RA-ILD in clinical practice. Interstitial lung disease (ILD) is an extra-articular manifestation of RA. The post-hoc investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD. This post-hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 21 Phase 1-4, and 2 long-term e...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Koz

August 20

Eficacia y Seguridad a Largo Plazo de Baricitinib con y sin Metotrexato para el Tratamiento de la Artritis Reumatoide: Experiencia con la Continuación de Baricitinib Monoterapia o Después del Cambio de Metotrexato Monoterapia o Baricitinib más Metotrexato

Fleischmann R, Takeuchi T, Schiff M, Schlichting D, Xie L, Issa M, Stoykov I, Lisse J, Martinez-Osuna P, Rooney T, Zerbini CAF.
Arthritis Care Res (Hoboken) 2020;72(8):1112-1121

This 24-week update from the baricitinib RA-BEYOND LTE study follows patients previously treated in the pivotal study RA-BEGIN. It demonstrates the maintained safety and efficacy of baricitinib monotherapy, and the effects of concurrent MTX treatment on response rates and patient reported outcomes. Previous P3 study RA-BEGIN demonstrated the superior efficacy of 4mg baricitinib compared to MTX monotherapy up to 52 weeks, with no major safety events being identified. At the end of the trial, pa...

Keywords: JAK, Baricitinib, Efficacy

Translated by: Igor Koz

Eficacia y Seguridad de Upadacitinib Monoterapia en Pacientes Metotrexato-Naïve con Artritis Reumatoide Moderada a Grave (SELECT- EARLY): Un Ensayo Aleatorizado, Doble-ciego, con Comparador Activo Multicéntrico Internacional

van Vollenhoven R, Takeuchi T, Pangan AL, Friedman A, Mohamed MEF, Chen S, Rischmueller M, Blanco R, Xavier RM, Strand V.
Arthritis Rheumatol 2020

Upadacitinib monotherapy demonstrated superior clinical, radiographic, and patient-reported outcomes versus methotrexate in methotrexate-naïve RA patients. This 48-week double-blind active comparator study investigated upadacitinib monotherapy in patients with early RA, who were either methotrexate-naïve, or who had very limited exposure. 947 patients were randomised to once-daily upadacitinib 15 or 30 mg, or weekly methotrexate. Unusually, there were two separate primary endpoints, s...

Keywords: JAK, Upadacitinib, Efficacy

Translated by: Igor Koz

July 20

Seguridad de DMARDs sintéticos y biológicos: una revisión sistemática de la literatura informando la actualización de 2019 de las recomendaciones EULAR para el tratamiento de la artritis reumatoide

Sepriano A, Kerschbaumer A, Smolen JS, Van Der Heijde D, Dougados M, Van Vollenhoven R, McInnes IB, Bijlsma JW, Burmester GR, De Wit M, Falzon L, Landewé R.
Annals of the Rheumatic Diseases 2020;79:760-770

This SLR informed the 2019 EULAR taskforce updating recommendations for RA management. Overall, no new safety signals were reported. The known safety profile of bDMARDs was confirmed and extended to tsDMARDS. IL-6i associated lower intestinal perforation has been further confirmed, while VTE and PE concerns in JAKi treatment need further evaluation. Previous updates for the EULAR recommendations on RA pharmacological management were conducted in 2016. In this SLR safety of csDMARDs, tsDMARDs, a...

Keywords: Safety

Translated by: Igor Koz

Tratamiento Farmacológico de la Artritis Psoriásica: Una Revisión Sistemática de la Literatura para la Actualización de las Recomendaciones EULAR del Tratamiento de la Artritis Psoriásica

Kerschbaumer A, Smolen JS, Dougados M, De Wit M, Primdahl J, McInnes I, Van Der Heijde D, Baraliakos X, Falzon L, Gossec L.
Annals of the Rheumatic Diseases 2020;79:778-786

This SLR reviewed data on pharmacological treatment of PsA. Findings informed the 2019 EULAR taskforce when updating recommendations for PsA management. Overall, no new safety signals were reported. Encouragingly, LTEs of JAKi did not report any venous thromboembolic events or PEs. Efficacy was demonstrated for a range of bDMARD and tsDMARD therapies in various disease domains. Efficacy varied between PsA manifestations and between therapies. Observational data demonstrated efficacy when switchi...

Keywords: Cytokine Signalling, Safety

Translated by: Igor Koz

COVID-19 Revisando las vías inflamatorias en artritis

Schett G, Manger B, Simon D, Caporali R.
Nat Rev Rheumatol 2020 doi.org/10.1038/s41584-020-0451-z

This review investigates the potential implications of COVID-19 on the field of rheumatology. Common pathways in COVID-19 and RA have provided rationale for the trial of DMARD therapies in treatment of severe COVID-19 infections. Safety considerations of RA patients undergoing immunomodulatory treatments are reviewed. Recommendations suggest that RA patients should continue DMARD treatment, whereas glucocorticoid use could be deleterious in COVID-19 infection and should be considered carefully, ...

Keywords: Cytokine Signalling

Translated by: Igor Koz

Seguridad y Eficacia de Tofacitinib en Pacientes con Artritis Psoriásica Activa: Análisis Provisional de OPAL Balance, un Estudio Abierto de Extensión a Largo Plazo

Nash P, Coates LC, Kivitz AJ, Mease PJ, Gladman DD, Covarrubias-Cobos JA, FitzGerald O, Fleishaker D, Wang C, Wu J, Hsu M, Menon S, Fallon L, Romero AB, Kanik KS.
Rheumatol Ther 2020 doi.org/10.1007/s40744-020-00209-4

This 3-year, open-label, LTE study follows PsA patients previously treated in pivotal studies OPAL Broaden and OPAL Beyond. It demonstrates maintained safety and efficacy of tofacitinib up to 36 and 30 months, respectively. No new safety concerns are highlighted. Previous P3 studies, OPAL Broaden and OPAL Beyond, demonstrated safety and efficacy of 5mg and 10mg tofacitinib BID in PsA. These patients rolled over to OPAL Balance for a period of 36 months. 686 participants were used in this inter...

Keywords: JAK, Tofacitinib, Safety

Translated by: Igor Koz

Retención del fármaco con 7 biológicos y tofacitinib en pacientes con artritis reumatoide naïve para biológicos y pacientes que cambiaron de biológicos: el estudio de cohorte ANSWER

Ebina K, Hirano T, Maeda Y, Yamamoto W, Hashimoto M, Murata K, Takeuchi T, Shiba H, Son Y, Amuro H, Onishi A, Akashi K, Hara R, Katayama M, Yamamoto K, Kumanogoh A, Hirao M.
Arthritis Res Ther 2020;22:142

This paper is based upon a long-term cohort study, namely the ANSWER cohort, an observational multi-centre registry of RA patients in the Kansai district of Japan. Analyses demonstrate a difference in observed drug retention between bDMARDs-naïve and bDMARDs-switched patients. 7 bDMARD treatments were compared in patients with no prior exposure to biologics, with abatacept showing the greatest retention rate. In patients that had switched between these same bDMARDs or to tofacitinib through...

Keywords: JAK, Tofacitinib

Translated by: Igor Koz

June 20

Eficiencia Comparada de los Agentes anti-factor de Necrosis Tumoral, Biológicos con un Modo de Acción Alternativo y Tofacitinib en una coorte observacional de pacientes con artritis reumatoide en Suiza

Finckh A, Tellenbach C, Herzog L, Scherer A, Moeller B, Ciurea A, von Muehlenen I, Gabay C, Kyburz D, Brulhart L, Müller R, Hasler P, Zufferey P.
RMD Open 2020;6:e001174 doi:10.1136/rmdopen-2020-001174

This nested cohort study found that, in Switzerland, there was a generally limited overall drug maintenance for b/tsDMARD options in RA. Using data from SCQM-RA – a prospective longitudinal registry, overall maintenance (drug survival) was calculated for TNFi, bDMARD-OMA or JAKi in patients with RA. After adjusting for potential confounding factors, there was a higher hazard of drug discontinuation with TNFi compared with tofacitinib; no significant difference was observed between non-TNF ...

Keywords: Cytokine Signalling, Real World, Efficacy

Translated by: Igor Kos

Interrupción Temporaria de Baricitinib: Caracterización de las Interrupciones y Efecto en los Desenlaces Clínicos de los Pacientes con Artritis Reumatoide

Emery P, Tanaka Y, Cardillo T, Schlichting D, Rooney T, Beattie S, Helt C, Smolen JS.
Arth Res Ther 2020;22:115 doi.org/10.1186/s13075-020-02199-8

This study aimed to characterize temporary interruptions of baricitinib and describe their impact on efficacy and safety. Brief interruptions during phase 3 baricitinib trials were associated with minor increases in symptoms which were resolved following treatment. In life-long, chronic conditions such as RA, interruption of therapy is common for various reasons, such as side effects, non-compliance, or because a patient requires surgery. Concerns have been raised that these treatment breaks c...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

Perfil de Seguridad de Baricitinib en el Tratamiento de Artritis Reumatoide a lo largo de una mediana de 3 años de tratamiento: Un análisis actualizado integrado de seguridad

Genovese MC, Smolen JS, Takeuchi T, Burmester G, Brinker D, Rooney TP, Zhong J, Daojun M, Saifan C, Cardoso A, Issa M, Wu W-S, Winthrop KL.
Lancet Rheumatol 2020;2:e347–57

RA is a chronic, life-long disease requiring long-term treatment. As such, it is important to understand the long-term safety profile of DMARDs. In this analysis, baricitinib maintained a stable safety profile during long-term exposure. This baricitinib safety analysis included integrated data from nine Phase 3, 2, and 1b clinical trials, and one long-term extension, with data up to 360 weeks. 3700 patients were included, with maximum follow-up of almost 7 years – representing an additio...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor Kos

Baricitinib en Pacientes con Artritis Reumatoide con Respuesta Inadecuada a Metotrexato: Resultados de un Estudio Fase 3

Li Z, Hu J, Bao C, Li X, Li X, Xu J, Spindler AJ, Zhang X, Xu J, He D, Li Z, Wang G, Yang Y, Wu H, Ji F, Tao H, Zhan L, Bai F, Rooney TP, Zerbini CAF.
Clin Exp Rheumatol . Jul-Aug 2020;38(4):732-741. Epub 2020 May 20.

This study conducted mainly in Chinese patients with RA, and an inadequate response to MTX, showed that baricitinib 4mg was associated with significant improvements and consistent with the findings from previous clinical trials. The efficacy and safety of baricitinib have been assessed in several clinical trials, predominantly in Caucasian populations. However, evidence on the efficacy and safety of baricitinib in Chinese patients is limited, with only one of the main clinical trial program stu...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

May 20

Fenebrutinib versus Placebo o Adalimumab en Artritis Reumatoide: Un estudio doble ciego aleatorizado de fase II (Estudio ANDES)

Cohen S, Tuckwell K, Katsumoto TR, Zhao R, Galanter J, Lee C, Rae J, Toth B, Ramamoorthi N, Hackney JA, Berman A, Damjanov N, Fedkov D, Jeka S, Chinn LW, Townsend MJ, Morimoto AM, Genovese MC.
Arthritis Rheumatol. 2020 Sep; 72(9): 1435–1446.

In this randomised phase II trial with MTX treatment-refractory RA patients, greater efficacy was observed with fenebrutinib 150 mg once daily or 200 mg twice daily compared to placebo, while response rates were numerically similar to those observed with adalimumab. BTK inhibitors have demonstrated clinical efficacy in B cell malignancies and multiple sclerosis, although there is limited clinical evidence of its efficacy in RA. Fenebrutinib (FEN) an orally active and selective non-covalent inh...

Keywords: BTK, Clinical, Phase 2

Translated by: Igor Koz

Evaluación del Virus Hepatitis B en Ensayos Clínicos de Baricitinib en Artritis Reumatoide

Harigai M, Winthrop K, Takeuchi T, Hsieh T-Y, Chen Y-M, Smolen JS, Burmester G, Walls C, Wu W-S, Dickson C, Liao R, Genovese MC.
RMD Open 2020;6:e001095

Although hepatitis B virus (HBV) reactivation was seen in patients with RA treated with DMARDs, including BARI, who had serology suggestive of prior infection, reactivation was transient even with continued BARI treatment and did not account for any clinically relevant AEs. Reactivation of HBV replication is a recognised complication in patients receiving biologic agents for RA, such as DMARDs. Limited data exist on prevalence of occult infection and the incidence of reactivation in RA patients...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor Koz

Análisis Integrado de Seguridad de Tofacitinib en Artritis Psoriásica en Estudios de Fase 3 y de Extensión a Largo Plazo y Comparación con Datos Observacionales de Mundo Real

Burmester GR, Curtis JR, Yun H, FitzGerald O, Winthrop KL, Azevedo VF, Rigby WFC, Kanik KS, Wang C, Biswas P, Jones T, Palmetto N, Hendrikx T, Menon S, Rojo R.
Drug Saf. 2020;43:379-392

Patients with psoriatic arthritis (PsA) had similar safety profile with TOF to that of other systemic therapies in real-world settings, except for the known risk of HZ. Treatment recommendations from EULAR and GRAPPA for patients with PsA vary according to adverse prognostic risk factors, disease manifestations and responsiveness to prior treatment. Safety concerns for most PsA therapies include gastrointestinal AEs, hepatotoxicity, opportunistic infections (OIs) including TB, and SIEs. This s...

Keywords: JAK, Tofacitinib, Real World, Safety

Translated by: Igor Koz

April 20

Eficacia y Seguridad Relativas de Tofacitinib, Baricitinib, Upadacitinib y Filgotinib en Comparación con Adalimumab en pacientes con Artritis Reumatoide Activa

Lee YH, Song GG.
Z Rheumatol. 2020 DOI: 10.1007/s00393-020-00750-1

This Bayesian network meta-analysis, comparing the relative efficacy and safety of JAK inhibitors, determined BARI 4mg + MTX and UPA 15mg + MTX were the most effective. The analysis included 5451 patients with an inadequate response to MTX and active RA, from four RCTs. Relative effects were converted into a probability allowing each treatment to be ranked. BARI and UPA had significantly higher ACR20 response rates than ADA 40mg + MTX whilst TOF 5mg and FIL 200mg had comparable ACR20 response ...

Keywords: JAK, Baricitinib

Translated by: Igor Koz

Efectividad a Largo Plazo de la Vacuna Viva Herpes Zoster en Pacientes con Artritis Reumatoide Tratados Posteriormente con Tofacitinib

Winthrop KL, Wouters A, Choy EH, Chen C, Biswas P, Wang L, Soma K, Needle E, Valdez H, Rigby WFC.
Ann Rheum Dis. 2020 10.1136/annrheumdis-2019-216566

The results of ORAL Sequel suggest that the live zoster vaccine (LZV) may not provide adequate long-term protection in patients with RA receiving TOF. This LTE study enrolled 100 patients with RA, 14 weeks post LZV vaccination. Patients received either TOF 5 mg BID, or TOF 10 mg BID in addition to any background csDMARDs. Incidence rates and 95% CIs for HZ post-vaccination were calculated based on time to first event. Short-term varicella zoster vaccine (VZV) specific immunity was evaluated a...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Koz

Vasculitis IgA como Efecto Adverso de Tofacitinib en Artritis Reumatoide

Itoh I, Kasuno K, Yamamoto C, Takahashi N, Shimizu H, Ojima T, Hayashi S, Kimura H, Iwano M.
Intern Med. 2020;59(6):817-821

Nephrotoxicity is a key side effect of NSAIDs and DMARDs used to treat RA, while biologics can reportedly cause proliferative glomerulonephritis or crescentic glomerulonephritis. This report reviews a patient on TOF presenting IgA vasculitis as an adverse effect that fully resolved following termination of TOF. Drug induced IgA vasculitis has been previously described for anti-TNFɑ therapies, but this is the first report with JAK inhibitor therapy. This is a case report of a 67-year old woman w...

Keywords: JAK, Tofacitinib, Real World, Safety

Translated by: Igor Koz

March 20

Exposición a Baricitinib Durante el Embarazo en Artritis Reumatoide

Costanzo G, Firinu D, Losa F, Deidda M, Barca MP, Del Giacco S.
Ther Adv Musculoskelet Dis. 2020;12:1759720X19899296

Broad and focused studies are required to have an insight of safety for small molecules, such as JAK inhibitors in the case of accidental exposure before or during pregnancy. This case study’s objective describes a case report of a 43-year-old woman affected by RA who became pregnant during BARI treatment. She has had two previous pregnancies at term without complications. After failure of bDMARDs due to loss of efficacy and adverse drug reactions, the patient was started on BARI when i...

Keywords: JAK, Baricitinib, Real World, Safety

Translated by: Igor Koz

Impacto de la Inhibición de Janus Quinasa con Tofacitinib en los Procesos Fundamentales de Regeneración Ósea

Gaber T, Brinkman ACK, Pienczikowski J, Diesing K, Damerau A, Pfeiffenberger M, Lang A, Ohrndorf S, Burmester G-R, Buttgereit F, Hoff P.
Int J Mol Sci 2020;21:865

TOF demonstrated a dose-dependent promotion of human mesenchymal stromal cell (hMSC) recruitment under hypoxia, while inhibiting recruitment under normoxia. TOF also dose-dependently enhances osteogenic differentiation of hMSCs and reduces osteoclast differentiation and activity. As people age, they are more likely to suffer from fractures and delayed bone healing, as well as degenerative joint diseases or osteoporosis. Bone metabolism and fracture healing may be negatively affected by underl...

Keywords: JAK, Tofacitinib, Clinical

Translated by: Igor Koz

La Inhibición JAK Aumenta la Masa Ósea en Condiciones de Estado Estacionário y Mejora la Pérdida Ósea Patológica al Estimular la Función de los Osteoblastos

Adam S, Simon N, Steffen U, Andes FT, Scholtysek C, Müller DIH, Weidner D, Andreev D, Kleyer A, Culemann S, Hahn M, Schett G, Krönke G, Frey S, Hueber AJ.
Sci Transl Med 2020;12(530):pii: eaay4447

JAKi significantly increased osteoblast function but showed no direct effects on osteoclasts. JAK signalling has emerged as an important therapeutic target for inflammatory disease, and the immunomodulation of JAK inhibition is well defined. Less well understood is the influence of this new class of drugs on bone homeostasis. This is important, as cytokine dysregulation triggers bone loss, and periarticular erosions contribute to the pathogenesis of RA. This study investigated the effect of B...

Keywords: JAK, Baricitinib, Preclinical

Translated by: Igor Koz

February 20

Recomendaciones EULAR para el Tratamiento de la Artritis Reumatoide – Actualización 2019 y Consenso acerca de los inhibidores JAK

Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, McInnes IB, Sepriano A, et al.
Ann Rheum Dis. 2020 Jan 22. pii: annrheumdis-2019-216655.

The EULAR recommendations for the management of RA have become increasingly useful in providing rheumatologists, patients, payers and other stakeholders with the evidence-based guidance and views of experts on the optimal use and sequence of pharmaceutical therapies in patients with RA. Over the course of the last decade, the evolution of the treatment landscape has already required two updates. The release of the new addition updates the 2016 recommendations. An international task force consid...

Keywords: JAK

Translated by: Igor Koz

Filgotinib, un Inhibidor JAK1, Modula Biomarcadores Relacionados con la Enfermedad en la Artritis Reumatoide: Resultados de 2 Estudios Aleatorizados, Controlados de Fase 2

Tarrant JM, Galien R, Wanying L, Goyal L, Pan Y, Hawtin R, Zhang W, Van der Aa A and Taylor PC.
Rheumatol Ther. 2020 DOI: 10.1007/s40744-019-00192-5

In this study examining the effect of FIL on a panel of biomarkers, FIL down-modulated several key inflammatory mediators of signalling pathways in RA - independent of MTX background therapy. This confirmed the strong network effects of the JAK1 node in autoimmunity, matrix and cartilage degradation, angiogenesis, and leukocyte adhesion and recruitment. Biomarkers key to RA pathophysiology were measured at baseline, Wk4 and Wk12 in FIL 100 mg, FIL 200 mg or PBO treatment groups from two phase ...

Keywords: JAK, Filgotinib, Clinical, Phase 2

Translated by: Igor Koz

Inhibición Preferencial de JAK1 en Relación a JAK 3 por Upadacitinib: Análisis de la Exposición-Respuesta de Datos Ex Vivo en 2 Ensayos Clínicos Fase 1 y Comparación con Tofacitinib

Mohamed MF, Beck D, Camp HS, Othman AA.
Pharmacodynamics. 2020

Ex vivo pharmacodynamic assay results demonstrated a greater selectivity of UPA on JAK1 versus JAK3 compared to TOF. This analysis conducted ex vivo stimulation of STAT3 phosphorylation by IL-6 as a measure of JAK1 activity and STAT5 phosphorylation by IL-7 as a measure of JAK1/JAK3 activity. Change in pSTAT3 and pSTAT5 were calculated at 1, 6 and 12 hours following drug administration using samples collected from healthy subjects and subjects with RA, from 2 phase 1 studies. Exposure-response...

Keywords: JAK, Upadacitinib, Preclinical, MOA

Translated by: Igor Kos

January 20

Seguridad, Tolerabilidad, Farmacocinética, Ocupación de Blanco y Análisis del Intervalo QT del Nuevo Inhibidor BTK Evobrutinib en Voluntarios Sanos

Becker A, Martin EC, Mitchell DY, Grennigloh R, Bender AT, Mackenzie H and Johne A.
Clin Transl Sci . 2020 Mar;13(2):325-336. doi: 10.1111/cts.12713. Epub 2019 Nov 29.

In this first in-human phase I, double-blind, placebo-controlled trial, the Bruton’s tyrosine kinase (BTK) inhibitor evobrutinib was well-tolerated, showed linear and time-independent PK, induced long-lasting BTK inhibition, and was not associated with prolongation of QT/QTc interval in healthy subjects. Evobrutinib is an oral BTK inhibitor that has demonstrated efficacy in pre-clinical and autoimmune disease models. BTK is a key regulator of B cell receptor and Fc receptor signalling, an...

Keywords: BTK, Clinical, Safety

Translated by: Igor Koz

Tofacitinib en Combinación con Metotrexato en Pacientes con Artritis Reumatoide: Resultados Reportados por los Pacientes del Estudio de Fase 3 de 24 Meses ORAL Scan

Strand V, van der Heijde D, Tanaka Y, Keystone E, Kremer J, Zerbini C A F, Cardiel M H, Cohen S, Nash P, Song Y-W, Tegzová D, Gruben D, Wallenstein G, Connell C A, Fleischmann R.
Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.

In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment. RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the ...

Keywords: JAK, Tofacitinib, Clinical, PRO

Translated by: Igor Koz

Efectos de Upadacitinib en los Resultados Reportados por los Pacientes: Resultados de SELECT-BEYOND, un Estudio clínico Aleatorizado de Fase 3 en Pacientes con Artritis Reumatoide y Respuesta Inadecuada a los Fármacos Antirreumáticos Modificadores de la Enfermedad

Strand V, Schiff M, Tunida N, Friedman A, Meerwein S, Pangan A, Ganguli A, Fuldeore M, Song Y, Pope J.
Arthritis Res Ther . 2019 Dec 2;21(1):263. doi: 10.1186/s13075-019-2059-8.

In SELECT-BEYOND, UPA demonstrated clinically meaningful improvements in patient reported outcomes compared to PBO in patients with RA who had an inadequate response to bDMARDs. In this post-hoc analysis of the SELECT-BEYOND study, the effect of UPA 15 or 30 mg on patient reported outcomes were assessed and compared to PBO. Eligible patients (498) with an inadequate response to bDMARDs were randomly assigned 1:1:1 to receive UPA 15 mg, UPA 30 mg or PBO. PROs collected at Wk1, Wk4, and Wk12 inclu...

Keywords: JAK, Upadacitinib, Clinical, PRO

Translated by: Igor Koz

Upadacitinib Mejora los Resultados Reportados por los Pacientes en Pacientes con Artritis Reumatoide y Respuesta Inadecuada a Fármacos Antirreumáticos Modificadores de la Enfermedad Sintéticos Convencionales: Resultados de SELECT-NEXT

Strand V, Pope J, Tundia N, Friedman A, Camp H, Pangan A, Ganguli A, Fuldeore M, Goldschmidt D, Schiff M.
Arthritis Res Ther . 2019 Dec 9;21(1):272.

In SELECT-NEXT, UPA demonstrated clinically meaningful improvements in patient reported outcomes compared to PBO in patients with RA who had an inadequate response to csDMARDs. In this post hoc analysis, the effect of UPA 15 or 30 mg on patient reported outcomes were assessed and compared to PBO. Eligible patients (661) with an inadequate response to csDMARDs were randomly assigned 2:2:1:1 to receive background csDMARD therapy with either UPA 15 mg, UPA 30 mg or PBO. PROs collected at Wk4 and Wk...

Keywords: JAK, Upadacitinib, Clinical, PRO

Translated by: Igor Koz

December 19

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study

Genovese MC, Greenwald MW, Gutierrez-Ureña SR.
Rheumatol Ther . 2019 Dec;6(4):503-520. doi: 10.1007/s40744-019-00167-6. Epub 2019 Aug 13.

Peficitinib (PEF) 100 mg QD demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA in a two-year extension of two global phase IIb studies. Patients enrolled in the LTE had completed one of two 12-week phase IIb PEF trials, one with MTX and one without. The primary objective of the LTE was to assess treatment-emergent adverse events and clinical laboratory evaluations for 105 weeks. As a secondary objective, an additional 2-years of effectivenes...

Safety of Baricitinib in East Asian Patients With Moderate to Severe Active Rheumatoid Arthritis: An Integrated Analysis From Clinical Trials

Chen YC, Yoo DH, Lee CK.
Int J Rheum Dis . 2020 Jan;23(1):65-73. doi: 10.1111/1756-185X.13748.

Post-hoc analyses of five completed phase II and III trials and an ongoing LTE suggested that BARI QD is well tolerated in East Asian patients with moderate-to-severe RA, with a similar safety and tolerability profile to the overall population. The majority of clinical evidence for RA treatments has been obtained from a predominantly Caucasian population, which may not be relevant to East Asian patients. In this post-hoc safety analysis, 740 Japanese, Taiwanese, Korean and Chinese patients were...

November 19

Análisis de Exposición Respuesta de Eficacia y Seguridad de Upadacitinib en Estudios de Fase 2 y 3 para Apoyar la Evaluación de Riesgo Beneficio en la Artritis Reumatoide

Nader A, Mohamed M-EF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA.
Clin Pharmacol Ther . 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671.

UPA 15 mg provided the optimal benefit-risk in RA through maximizing efficacy with only small incremental benefit with 30 mg, and with consistency across RA subpopulations and with UPA monotherapy or combination with csDMARDs. Exposure-response analyses were conducted using combined data from two Phase 2b and five Phase 3 studies in order to characterise the relationship between plasma exposure and efficacy, as well as to select safety parameters using the totality of the data in subjects with...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

Translated by: Igor Kos

Eficacia Comparativa de Peficitinib 25, 50, 100 y 150mg en Pacientes con Artritis Reumatoide Activa: Un Metaanálisis Bayesiano en Red de Ensayos Controlados Aleatorizados

Lee YH, Song GG.
Clin Drug Investig .2020 Jan;40(1):65-72. doi: 10.1007/s40261-019-00863-9.

TOF significantly modulated the Th1 response to Varicella-zoster-virus (VZV). The poor VZV-specific cellular immune responses in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response. Previous studies have shown that treatment with JAKinibs increases HZ incidence compared with conventional DMARDs. This cross-sectional in vitro study aimed to investigate the effect of TOF on the VZV-specific T cell immune re...

Keywords: JAK, Peficitinib, Clinical, Efficacy

Translated by: Igor Kos

Una revisión sistemática y metaanálisis del riesgo de infección con los inhibidores de JAK moléculas pequeñas en artritis reumatoide

Bechman K, Subesinghe S, Norton S, Atzeni F, Galli M, Cope AP, Winthrop KL, Galloway JB.
Rheumatology (Oxford) 2019;58(10):1755–66

Absolute serious infection rates were low. However, across the JAKinibs, the incidence of HZ is higher than expected for the population. While the risk was numerically greatest with BARI, indirect comparisons between the drugs did not demonstrate any significant difference in risk. How JAKinibs increase the risk of HZ reactivation is unclear, but how different JAKs interact in the immune response suggest that there may be differences in safety profiles between JAKinib drugs, underpinned by the...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor Kos

Eficacia Comparativa de Peficitinib 25, 50, 100 y 150mg en Pacientes con Artritis Reumatoide Activa: Un Metaanálisis Bayesiano en Red de Ensayos Controlados Aleatorizados

Almanzar A, Kienle F, Schmalzing M, Maas A, Tony H-P, Prelog M.
Rheumatology (Oxford) 2019;58(11):2051–60

TOF significantly modulated the Th1 response to Varicella-zoster-virus (VZV). The poor VZV-specific cellular immune responses in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response. Previous studies have shown that treatment with JAKinibs increases HZ incidence compared with conventional DMARDs. This cross-sectional in vitro study aimed to investigate the effect of TOF on the VZV-specific T cell immune re...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

October 19

Factores de Riesgo para Eventos Cardiovasculares Mayores en los Estudios de Extensión a Largo Plazo y de Fase III de Tofacitinib en Pacientes con Artritis Reumatoide

Christina Charles-Schoeman, Ryan DeMasi, Hernan Valdez, Koshika Soma, Lie-Ju Hwang, Mary G Boy, Pinaki Biswas, Iain B McInnes.
Arthritis Rheumatol .2019 Sep;71(9):1450-1459. doi: 10.1002/art.40911. Epub 2019 Aug 6.

Post hoc analyses of the six ORAL studies and two LTE’s suggested that after 24 weeks of TOF treatment, increases in HDL-c and decreases in the TC/HDL-c ratio appeared to be associated with reduced future MACE risk in RA patients. 52 MACE occurred in 4076 patients over 12873 patient-years of exposure. Separate Cox regression models were used to evaluate traditional CV risk factors’ association with time to first MACE at baseline and changes in lipid levels with time to future MACE ...

Keywords: JAK, Tofacitinib, Real World, Cardiovascular

Translated by: Igor Koz

Changes in Lipid Levels and Incidence of Cardiovascular Events Following Tofacitinib Treatment in Patients with Psoriatic Arthritis: A Pooled Analysis Across Phase 3 and Long-Term Extension Studies

Gladman DD, Charles-Schoeman C, McInnes IB, Veale DJ, Thiers B, Nurmohamed M, Graham D, Wang C, Jones T, Wolk R, DeMasi R.
Arthritis Care Res (Hoboken) 2019;71(10):1387–95

Serum lipid level increases at month 3 following TOF treatment in PsA were consistent with observation in RA and psoriasis. The risk of CV disease is higher in people with PsA versus the general population – comparable with the well-documented rates seen in RA and diabetes. The reasons for this are not fully elucidated, but it has been suggested that there is an association between peripheral joint inflammation and lipid dysregulation in PsA. This post hoc analysis of pooled data from ...

Efecto de Baricitinib y Adalimumab en la Reducción del Dolor y en la Mejora de la Función en Pacientes con Artritis Reumatoide con Baja Actividad de la Enfermedad: Análisis Exploratorio de RA-BEAM

Fautrel B, Kirkham B, Pope JE, Takeuchi T, Gaich C, Quebe A, Zhu B, de la Torre I, De Leonardis F, Taylor PC.
J Clin Med. 2019 Sep 5;8(9). pii: E1394

Post hoc analyses from RA-BEAM concluded that BARI 4 mg QD or ADA 40 mg Q2W resulted in improvements in pain, physical function, fatigue and work productivity in patients with RA, independent of the treatment’s impact on inflammation. Among patients achieving remission or LDA, greater improvements in pain and physical function were seen with BARI than with ADA or PBO. Of 1010 patients included in the analysis at Week 24, 168 were in remission, 310 were in remission/LDA and 700 were not in...

Keywords: JAK, Baricitinib, Clinical, PRO

Translated by: Igor Koz

September 19

Resultados de la Reducción de Dosis, Retirada y Reinicio de Tofacitinib en Pacientes con Artritis Reumatoide: Un Estudio Prospectivo Observacional

Mori S, Ueki Y.
Clin Rheumatol. 2019 Aug 9. DOI: 10.1007/s10067-019-04721-z

Following achievement of remission or low disease activity (LDA), a dose reduction strategy of TOF to a 5mg QD dose was preferable to immediate withdrawal of TOF, with lower relapse rates. Clinical remission or LDA early in the disease course is a target for every RA patient. Although maintaining a state of remission or LDA is beneficial to patients, the AEs and costs associated with DMARDs, have significant burdens on patients during life-long RA treatment. This long-term study was performed t...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Comparación de la Regulación de la Señalización de Citoquinas Mediada por Baricitinib, Upadactinib y Tofacitinib en Subpoblaciones de Leucocitos Humanos

McInnes IB, Byers NL, Higgs RE, Lee J, Macias WL, Na S, Ortmann RA, Rocha G, Rooney TP, Wehrman T, Zhang X, Zuckerman SH, Taylor PC.
Arthritis Res Ther. 2019 Aug 2;21(1):183

Different JAKinibs modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signalling pathway throughout the dosing interval. This study aimed to compare the in vitro cellular pharmacology of BARI, TOF and UPA across relevant leukocyte subpopulations, coupled with their in vivo PK, to determine their effects on distinct cytokine pathways. Peripheral blood mononuclear cells from healthy donors were incubated with differen...

Keywords: JAK, Upadacitinib, Preclinical, Selectivity

Translated by: Igor Koz

August 19

Eficacia y Seguridad de Peficitinib (ASP015K) en Pacientes con Artritis Reumatoide con Respuesta Inadecuada a Metotrexate: Resultados de un Estudio Fase III Aleatorizado, Doble-Ciego, controlado con Placebo (RAJ4) en Japán

Takeuchi T, Tanaka Y, Tanaka S, Kawakami A, Iwasaki M, Katayama K, Rokuda M, Izutsu H, Ushijima S, Kaneko Y, Shiomi T, Yamada E, van der Heijde D.
Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

Peficitinib (PEF) 100 and 150 mg demonstrated robust clinical and structural efficacy in patients with RA who have an inadequate response to MTX. In Japan, two JAK inhibitors, TOF and BARI are currently available for RA patients with an inadequate response to conventional therapies. This randomized phase 3 study (RAJ4), assessed the efficacy and safety of two PEF doses in combination with MTX compared to PBO, in Japanese MTX-IR. Patients were randomized 1:1:1 to PBO, PEF 100 mg and 150 mg with...

Keywords: JAK, Peficitinib, Clinical, Phase 3

Translated by: Igor Koz

Efecto de FIlgonitib vs Placebo en la Respuesta Clínica en Pacientes con Artritis Reumatoide Moderada a Grave Refractaria a una Terapia con Fármacos Antirreumáticos Modificadores de la Enfermedad: El Estudio Aleatorizado FINCH 2

Genovese MC, Kalunian K, Gottenberg JE, Mozaffarian N, �Bartok B, Matzkies F, Gao J, Guo Y, Tasset C, Sundy JS, de Vlam K, Walker D, Takeuchi T.
JAMA 2019 322(4):315-325

Among RA patients with an inadequate response or intolerance to bDMARDs, filgotinib (FIL) doses, compared to PBO resulted in significantly greater proportions achieving a clinical response at Wk12. Patients with active RA despite treatment with bDMARD therapy need treatment options. The FINCH 2 Phase 3 study compared the effects of FIL vs PBO for the treatment of RA patients with inadequate response or intolerance to ≥1 prior bDMARDs. Patients were randomized in a 1:1:1 ratio, receiving FI...

Keywords: JAK, Filgotinib, Clinical, Efficacy

Upadacitinib versus Placebo o Adalimumab en Pacientes con Artritis Reumatoide y una Respuesta inadecuada a Metotrexate: Resultados de un Estudio de Fase 3, aleatorizado, controlado doble ciego

Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC.
Arthritis Rheumatol 2019 DOI: 10.1002/art.41032

UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key e...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

Seguridad y Efectividad de Upadacitinib o Adalimumab más Metotrexate en Pacientes con Artritis Reumatoide: Más de 48 Semanas de Troca para una Terapia Alternativa con Respuesta Insuficiente

Fleischmann RM, Genovese MC,  Enejosa JV,  Mysler E, Bessette L, Peterfy C,  Ostor P,  Li Y,  Song I.
Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR. 1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, ...

Keywords: JAK, Upadacitinib, Clinical, Efficacy

July 19

Vacuna Viva Zoster en Pacientes con Artritis Reumatoide Tratados con Tofacitinib con o sin Metotrexato, o Adalimumab con Metotrexato

Calabrese LH, Abud-Mendoza C, Lindsey SM, Lee SH, Tatulych S, Takiya L, Iikuni N, Soma K, Luo Z, Fleischmann R.
Arthritis Care and Research 2019 DOI: 10.1002/acr.24010

Live zoster vaccine (LZV) was well tolerated, and herpes zoster (HZ) incidence rates were generally similar between treatment groups in vaccinated versus non-vaccinated patients in a subset of RA who received LZV before TOF ± MTX, or ADA + MTX, in ORAL Strategy. It is known that patient with RA are at increased risk of developing HZ though the mechanisms behind this are currently not well understood though therapies, such as TOF, are thought to increase the risk. ACR and EULAR recommend...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

Desenlaces Clínicos en Pacientes que Cambiaron de Adalimumab a Baricitinib debido a falta de respuesta y/o Diseño del Estudio: Fase 3 en Pacientes con Artritis Reumatoide

Tanaka Y, Fautrel B, Keystone EC, Ortmann RA, Xie L, Zhu B, Issa M, Patel H, Gaich CL, de Bono S, Rooney TP, Taylor PC.
Ann Rheum Dis. 2019 Jul;78(7):890-898.

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching fro...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Igor

June 19

Efficacy and Safety of Filgotinib for Patients With Rheumatoid Arthritis Naïve to Methotrexate Therapy: FINCH 3 Primary Outcome Results

Westhovens R, Rigby WFC, van der Heijde D, Ching DWT, Bartok B, Matzkies F, Yin Z, Guo Y, Tasset C, Sundy JS, Mozaffarian N, Messina OD, Landewé RBM, Atsumi T, Burmester GR.
EULAR 2019 Abstract LB0003 Presentation

Filgotinib is an orally administered, selective inhibitor of JAK1. Filgotinib has shown good efficacy and was well tolerated for the treatment of RA in Phase 2 and 3 studies evaluating MTX-IR or bDMARD-IR patients. The objective of this study was to compare the efficacy and safety of filgotinib with and without MTX in patients with RA who were naïve to MTX therapy.

Efficacy and Safety of Filgotinib for Patients With Rheumatoid Arthritis With Inadequate Response to Methotrexate: FINCH 1 Primary Outcome Results

Combe BG, Kivitiz AJ, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy JS, Mozaffarian N, Landewé RBM, Bae SC, Keystone EC, Nash P.
EULAR 2019 Abstract LB0001 Presentation

Filgotinib is an orally administered, selective inhibitor of JAK1. Filgotinib has shown good efficacy and was well tolerated for the treatment of rheumatoid arthritis (RA) in Phase 2 studies.The objective of this Phase 3 study was to evaluate the efficacy and safety of filgotinib treatment in patients with RA who have had an inadequate response to methotrexate (MTX).

Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models

Haselmayer P, Camps M, Liu-Bujalski L, Nguyen N, Morandi F, Head J, O’Mahony A, Zimmerli SC, Bruns L, Bender AT, Schroeder P, Grenningloh.
J Immunol 2019;202:2888–2906. DOI: 10.4049/jimmunol.1800583

BTK is involved in both adaptive and innate immune responses and mediates signalling of several immune receptors of relevance to RA and SLE pathogenesis. Targeting BTK is a promising approach therefore for autoimmune disorders with aberrant B cell responses. Evobrutinib is a novel, highly specific, and irreversible BTK inhibitor. In vivo and animal models showed that evobrutinib modulated B cell and innate immune cell activation, was efficacious, and prevented joint damage. The potency of evob...

Impacto de los Inhibidores de Janus Quinasa en el Riesgo de Eventos Cardiovasculares en Pacientes con Artritis Reumatoide: Revisión Sistemática y Metaanálisis de Ensayos Controlados Aleatorizados

Xie W, Huang Y, Xiao S, Sun X, Fan Y, Zhang Z.
Ann Rheum Dis. 2019 Aug;78(8):1048-1054.

Existing evidence from RCTs indicated no significant change in CV risk for JAK inhibitor (JAKinib) treated RA patients in a short-term perspective compared to placebo. Patients with RA have an elevated risk of CV morbidity and mortality, which cannot be fully explained by traditional CV risk factors. Reaching remission or LDA in order to reduce CV events (CVE) is encouraged in the current EULAR recommendations. JAKinibs and their roles in the modulation of CV risk remain undetermined. This stud...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

Upadacitinib as Monotherapy in Patients with Active Rheumatoid Arthritis and Inadequate Response to Methotrexate (SELECT-MONOTHERAPY): A Randomised, Placebo-Controlled, Double-Blind Phase 3 Study

Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA, Camp HS, Cohen S.
Lancet. 2019 Jun 8;393(10188):2303-2311

UPA monotherapy showed statistically significant improvements in clinical and functional outcomes versus continuing MTX in MTX inadequate-responder patients with RA. Despite its proven effectiveness and safety, many patients are unable to tolerate MTX due to its side-effects. Therapies that can be used without concomitant MTX therefore, have an important place in RA management. In previous studies, UPA has shown efficacy in combination with stable background csDMARDs in RA patients who are DMA...

May 19

Una Revisión Sistemática y Metaanálisis del Riesgo de Infecciones con Moléculas Pequeñas Inhibidoras de JAK en Artritis Reumatoide

Bechman K, Subesinghe S, Norton S, Atzeni F, Galli M, Cope AP, Winthrop KL, Galloway JB.
Rheumatology (Oxford). DOI: 10.1093/rheumatology/kez087

How JAKinibs increase the risk of HZ reactivation is unclear. Roles of different JAKs in the immune response may suggest differences in safety profiles between drugs, underpinned by their differential JAK selectivity profiles. The authors undertook a systematic review and meta-analysis to evaluate SI and opportunistic indicator infections including HZ in RA Phase II/III clinic trials with JAKinibs. A literature review of RCT of TOF (5 mg BID), BARI (4 mg OD) and UPA (15 mg OD) was conducted. A...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

Safety and Efficacy of Tofacitinib For Up to 9.5 Years in The Treatment of Rheumatoid Arthritis: Final Results of a Global, Open-Label, Long-Term Extension Study

Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, Mojcik C, DeMasi R, Strengholt S, Kwok K, Lazariciu I, Wang L, Cohen S.
Arthritis Res Ther. 2019 Apr 5;21(1):89.

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study. TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of ...

Evaluación de las Respuestas Vacunales Neumocócica y Antitetánica en Pacientes con Artritis Reumatoide recibiendo Baricitinib: Resultados de un Subestudiode Extensión

Winthrop KL, Bingham CO III, Komocsar WJ, Bradley J, Issa M, Klar R, Kartman CE.
Arthritis Res Ther. 2019 Apr 18;21(1):102

Approximately two thirds of long-term BARI treated patients achieved satisfactory humoral and functional responses to 13-serotype pneumococcal conjugate vaccine (PCV-13), whereas tetanus toxoid vaccine (TTV) responses were less robust. Both RA management guidelines and recommendations suggest vaccinating patients with RA against pneumococcal disease with PCV-13 and PPSV-23. The inhibition of the JAK mediated signal transduction pathways in RA treatment could diminish vaccine responses. Given t...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

April 19

Tuberculosis, Hepatitis B y Herpes Zoster en Pacientes con Artritis Reumatoide tratados con Tofacitinib

Zhang Z, Deng W, Wu Q, Sun L.
Immunotherapy. 2019 Mar;11(4):321-333.

The risk of TB and hepatitis B virus (HBV) appears to be no greater with TOF than with bDMARDs. Most cases of TB during TOF studies occurred in regions with high background rate of TB, including east Asian countries. TOF is also associated with a higher rate of herpes zoster (HZ) compared with bDMARDs. DMARDs used to treat RA can increase the risk of infections by causing a degree of immunosuppression. A range of bacterial and viral infections have been observed in association with DMARD thera...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

Datos de Eficacia y Seguridad Basados en Historial Medico o Enfermedades Pre-Existentes en el Baseline de Pacientes con Artritis Reumatoide Activa Tratados con Baricitinib

Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M.
Ann Rheum Dis. 2019 Aug;78(8):1135-1138.

In a post-hoc analysis, BARI 4 mg showed similar efficacy and safety during placebo-controlled and LTE observation periods regardless of the presence or absence of select comorbidities in RA patients. Patients with RA have a high prevalence of comorbidities. This post-hoc analysis investigated the effect of select comorbidities (depression, osteoporosis, hepatic, cardiovascular or pulmonary disorders) on the efficacy and safety of BARI 4 mg QD in patients with moderate-to-severe active RA and i...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

March 19

Perfil de Seguridad de Baricitinib en Pacientes Japoneses con Artritis Reumatoide Activa con más de 1.6 años de Tiempo Medio de Tratamiento: Un análisis integrado de Estudios Fase 2 y 3

Harigai M, Takeuchi T, Smolen JS, Winthrop KL, Nishikawa A, Rooney TP, Saifan CG, Issa M, Isaka Y, Akashi N, Ishii T, Tanaka Y.
Mod Rheumatol. 2019 Feb 20:1-23. DOI: 10.1080/14397595.2019.1583711

In this integrated analysis, BARI showed an acceptable safety profile in Japanese patients with up to 3.2 years of exposure. Other than incidences of herpes zoster (HZ), no major differences were noted with BARI safety in Japanese patients with RA, compared to the patients in the integrated database. BARI has previously demonstrated significant clinical efficacy and acceptable safety. Japanese patients who participated in the BARI clinical development programme, were comparable to those from th...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

Baricitinib induce incrementos en LDL-C y HDL-C en Artritis Reumatoide: Un Metaanálisis en red de Ensayos Clínicos Aleatorizados

Qiu C, Zhao X, She L, Shi Z, Deng Z, Tan L, Tu X, Jiang S, Tang B.
Lipids Health Dis. 2019 Feb 18;18(1):54.

This study confirmed that BARI induced a stable dose-dependent increase in LDL-C and HDL-C levels. There was no significant difference of CV risk between BARI and placebo groups. High risk of CV events is strongly associated with RA. Mechanisms underlying the excess risk of CV events in RA remains unclear. This study aims to provide additional insight into the clinical safety of BARI, focusing on the effects of BARI on LDL-C and HDL-C levels and CV risk. A Cochrane analysis was performed on s...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

Metanálisis en Red de Tofacitinib versus Tratamientos Biológicos en Pacientes con Artritis Reumatoide Moderada a Grave

Camean‐Castillo M, Gimeno‐Ballester V, Rios‐Sanchez E, Fenix‐Caballero S, Vázquez‐Real M, Alegre‐del Rey E.
J Clin Pharm Ther. 2019 Jun;44(3):384-396.

This study suggests that many bDMARDs and tsDMARDs can be considered equivalent therapeutic alternatives in bDMARD-naïve RA patients, with inadequate response to csDMARDs. In the absence of randomised controlled trials comparing drugs, indirect comparisons and network meta-analysis may provide information to help select an optimal treatment alternative. In this network meta-analysis, 27 randomized controlled trials were analysed to assess the possibility that some drugs on the market may b...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Igor

February 19

Risk of Serious Infection in Patients with Rheumatoid Arthritis in Routine Care with Abatacept, Rituximab and Tocilizumab in Denmark and Sweden

Grøn KL, Arkema EV, Glintborg B, Mehnert F, Østergaard M, Dreyer L, Nørgaard M, Krogh NS, Askling J, Hetland ML, ARTIS Study Group.
Ann Rheum Dis. 2019 Mar;78(3):320-327. DOI: 10.1136/annrheumdis-2018-214326

Differences in baseline characteristics and numerical differences in IR of SI between ABA, RRTX and TOZ were observed. The relative risk (RR) of SIs seemed to vary modestly with drug. TNFi treated RA patients in large observational studies have suggested an initial twofold increased risk of SIs compared with biologic-naïve patients. Long-term observational studies on the risk of SIs in patients treated with non-TNFi bDMARDs are sparse. This study aimed to estimate crude as well as age and...

Comparisons of Hepatitis C Viral Replication in Patients with Rheumatoid Arthritis Receiving Tocilizumab, Abatacept and Tofacitinib Therapy

Chen YM, Huang WN, Liao TL, Chen JP, Yang SS, Chen HH, Hsieh TY, Hung WT, Chen YH, Chen DY.
Ann Rheum Dis. 2019 Jun;78(6):849-850.

Tocilizumab (TCZ), abatacept (ABA) and tofacitinib (TOF) appear to have no major safety concerns for treatment of RA patients with hepatitis C virus (HCV) infections. HCV is an infectious disease which continues to present a major therapeutic challenge for clinicians in treating patients with RA. Previous reports demonstrate that the use of TNF targeted therapies in RA patients with HCV infections appear to have no major safety concerns. During short-term therapy with TCZ and ABA, data has show...

Tofacitinib in Combination with Methotrexate in Patients with Rheumatoid Arthritis: Clinical Efficacy, Radiographic and Safety Outcomes from the 24-Month Phase 3 ORAL Scan Study

van der Heijde D, Strand V, Tanaka Y, Keystone E, Kremer J, Zerbini CAF, Cardiel MH, Stanley Cohen S, Nash P, Song YW, Tegzová D, Gruben D, Wallenstein G, Connell CA, Fleischmann R, ORAL Scan investigators.
Arthritis Rheumatol. 2019 Jun;71(6):878-891

RA patients receiving TOF 5 or 10 mg BID plus MTX showed sustained clinical and radiographic treatment effects through months 12-24. The safety profile was consistent with previous TOF studies. The 12-month data from the ORAL Scan study have been previously reported. This report assesses durability of responses, including structural damage progression, and safety with TOF through 24 months. Patients were randomized 4:4:1:1 to receive TOF 5 or 10 mg BID, or PBO advanced to TOF with stable, ba...

Cardiovascular Safety During Treatment with Baricitinib in Rheumatoid Arthritis

Taylor PC, Weinblatt ME, Burmester GR, Rooney TP, Witt S, Walls CD, Issa M, Salinas CA, Saifan C, Zhang X, Cardoso A, González-Gay MA, Takeuchi T.
Arthritis Rheumatol. 2019 Jul;71(7):1042-1055.

This study indicates no association between exposure to BARI and MACE, arterial thrombotic events (ATE), or congestive heart failure (CHF). Overall IRs for venous thromboembolic event (VTE) in BARI-treated patients falls within the reported range for patients with RA. RA patients have a greater risk of cardiovascular (CV) diseases of arterial ischemic origin, and an increased risk of VTE. Studied frequencies of thromboembolic events in RA populations in the last decade has been reported as 2&nd...

January 19

Análisis agrupado de la seguridad de Tofacitinib como monoterapia o en combinación con Fármacos Antirreumáticos Modificadores de la Enfermedad Convencionales de base en una Población de Fase 3 con Artritis Reumatoide

Kivitz AJ, Cohen S, Keystone E, van Vollenhoven RF, Haraoui B, Kaine J, Fan H, Connell CA, Bananis E, Takiya L, Fleischmann R.
Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006.

In this pooled analysis of Phase 3 Tofacitinib (TOF) trials, safety profiles were generally similar between patients receiving monotherapy and combination therapy. Although selected adverse events of interest showed lower incidence rates (IRs) for TOF monotherapy patients. TOF has been studied as monotherapy and in combination with csDMARDs. In this post-hoc analysis, data were pooled from six Phase 3 TOF studies in RA patients to further examine the safety profile when used as monotherapy or i...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

Caracterización y Cambios en Subconjuntos de Linfocitos en Pacientes con Artritis Reumatoide Tratados con Baricitinib: Un Análisis Integrado

Tanaka Y, McInnes IB, Taylor PC, Byers NL, Chen L, de Bono S, Issa M, Macias WL, Rogai V, Rooney TP, Schlichting DE, Zuckerman SH, Emery P.
Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

This review shows that changes in lymphocyte subsets were largely within normal reference ranges and were not associated with efficacy or safety end points. BARI is a selective JAK1/JAK2 inhibitor, approved for the treatment of moderate to severe RA. BARI treatment is associated with changes to circulating lymphocyte and lymphocyte subsets, however detailed analyses of these effects, and their relevance to efficacy and safety is lacking. This study investigated the changes in lymphocyte cell s...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor

Riesgo Comparativo de Tromboembolismo Venoso con Tofacitinib versus con Inhibidor de Factor de Necrosis Tumoral: Un Estudio de Cohorte de Pacientes con Artritis Reumatoide

Desai RJ, Pawar A, Weinblatt ME, Kim SC.
Desai RJ, et al. Arthritis Rheumatol. 2019 June;71(6):892-900.

Occurrences of venous thromboembolism (VTE) in 50, 865 RA patients initiating Tofacitinib (TOF) or a TNF inhibitor (TNFi) was infrequent. No significant risk of VTE for TOF versus TNFi was observed. Safety concerns of JAK inhibitor BARI include potentially increased risk of VTE at the higher 4 mg dose. It’s unclear if this is attributable to JAK-inhibition and extends to TOF. This study compared the risk of VTE with TOF, versus TNFi in real-world settings with RA patients. RA patients in...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

December 18

Evaluación de Efectos a Corto, Medio y Largo-plazo de Tofacitinib en Linfocitos de Pacientes con Artritis Reumatoide

van Vollenhoven R, Lee EB, Strengholt S, Mojcik C, Valdez H, Krishnaswami S, Biswas P, Lazariciu I, Hazra A, Clark JD, Hodge J, Wang L, Choy E.
Arthritis Rheumatol 2018 DOI: 10. 1002/art.40780

Tofacitinib (TOF) treatment is associated with short-term transient increases in absolute lymphocyte counts (ALC), followed by a gradual decline to reach steady state by ~48 months. Changes in both ALC and lymphocyte subset counts (LSC) were reversible upon TOF discontinuation. Low ALC but not LSC were associated with an increased risk of serious infective episodes (SIEs) and herpes zoster (HZ). This data supported the treatment recommendations on ALC counts for starting and continuing therapy w...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor

Influencia de la Edad y del Daño Renal en la Farmacocinética de Estado Estable de Filgotinib, un inhibidor selectivo de JAK1

Namour F, Fagard L, Van der AA, Harrison P, Xin Y, Tasset C.
Br J Clin Pharmacol 2018 Dec;84(12):2779-2789. DOI:10.1111/bcp.13726

Age and renal impairment (RI) had limited impact on the pharmacokinetics (PK) of filgotinib (FIL) but, in subjects with severe RI, exposure to the FIL metabolite was increased. FIL is a selective JAK1 inhibitor that is extensively, rapidly and proportionately absorbed after oral dosing from 50–200mg. Its major metabolite has a similar JAK1 selectivity profile but with reduced potency. In humans, exposure to the metabolite is higher by approximately 16–20 fold compared with the pare...

Keywords: JAK, Filgotinib, Preclinical, PK-PD

Translated by: Igor

November 18

Seguridad y Eficacia de Baricitinib en Pacientes Recibiendo Fármacos Antirreumáticos Modificadores de la Enfermedad o Corticoides

van Vollenhoven R, Helt C, Arora V, Zhong J, Correia AP, de la Torre I, Muram D.
Rheumatol Ther 2018 Dec;5(2):525-536. DOI 10.1007/s40744-018-0128-0

Baricitinib (BARI) in combination with MTX and concomitant csDMARDs was shown to be efficacious, regardless of corticosteroid use in RA patients. MTX is prescribed to most RA patients but concomitant csDMARDs and/or corticosteroids can be added. This study assessed the efficacy and safety of BARI in two arms; with/without corticosteroids and; with MTX only/MTX plus csDMARD/csDMARDs only. Baseline characteristics and adverse reactions were also compared. Data were pooled from two phase 3 studie...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Igor Kos

Herpes Zoster con Tofacitinib está aún más Aumentado con Glucocorticoides pero no con Metotrexate

Curtis JR, Xie F, Yang S, Bernatsky S, Chen L, Yun H, Winthrop K.
Arthritis Care Res 2018 DOI 10.1002/acr.23769

The rate of Herpes Zoster (HZ) in tofacitinib (TOF) users with concomitant glucocorticoids (GC) was approximately double that of other TOF combination therapies. TOF is an effective treatment for RA. Increased HZ risk has been observed with the use of JAK inhibitors, whereas the HZ risk with biologics and targeted RA therapies are comparable. This study evaluated the HZ risk in TOF users according to concomitant GC, MTX, both, or neither. MarketScan and Medicare data were used to identify 8030 ...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Ankylosing Spondylitis (TORTUGA): Results from a Randomized, Placebo-controlled, Phase 2 Trial

Van der Heijde D, Baraliakos X, Gensler LS, Maksymowych WP, Tseluyko V, Nadashkevich O, Abi-Saab W, Tasset C, Meuleners L, Besuyen R, Hendrikx T, Mozafarian N, Liu K, Greer JM, Deodhar A, Landewé R.
Lancet 2018 Dec 1;392(10162):2378-2387. DOI 10.1016/S0140-6736(18)32463-2

In this first clinical trial of filgotinib in patients with active AS, filgotinib significantly reduced disease activity, and the signs and symptoms of AS compared with placebo. The TORTUGA trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 263 adult patients from 30 sites in seven countries. Patients with active AS and an inadequate response or intolerance to two or more NSAIDs were assigned 1:1 to receive filgotinib 200 mg or placebo once daily for 12 week...

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Psoriatic Arthritis (EQUATOR): Results from a Randomised, Placebo-controlled, Phase 2 Trial

Mease P, Coates LC, Helliwell PS, Stanislavchuk M, Rychlewska-Hanczewska A, Dudek A, Abi-Saab W, Tasset C, Meuleners L, Harrison P, Besuyen R, Van der Aa A, Mozafarian N, Greer JM, Kunder R, Van den Bosch F, Gladman DD.
Lancet. 2018 Dec 1;392(10162):2367-2377. DOI 10.1016/ S0140-6736(18)32483-8

In this first clinical trial of filgotinib in patients with PsA, filgotinib was effective in treating the signs and symptoms of active PsA across various disease manifestations. The EQUATOR trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 191 adult patients from 25 sites in seven countries. Patients with active moderate-to-severe PsA and an insufficient response or intolerance to at least one csDMARD were assigned 1:1 to receive filgotinib 200 mg or placebo...

October 18

Comparación de la Eficácia y Seguridad de Tofacitinib y Baricitinib en Pacientes con Artritis Reumatoide Activa: Un Metaanálisis Bayesiano en Red de Ensayos Controlados Aleatorizados

Bae SC and Lee YH.
Z Rheumatol. 2018 Sep 6. DOI 10.1007/s00393-018-0531-5

Tofacitinib (TOF) 10mg and baricitinib (BARI) 4mg, in combination with methotrexate (MTX), were the most efficacious treatments in RA patients with an inadequate response to DMARDs or biologics. Both combination treatments presented acceptable safety profiles and were not associated with a significant risk of serious adverse events. This study employed a Bayesian approach to Meta-Analysis; combining the available evidence across a network of Randomised Controlled trials (RCTs). Twelve RCTs cont...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Igor Kos

Reducción de Dosis de Baricitinib en Pacientes con Artritis Reumatoide Logrando Controle Sostenido de la Enfermedad: Resultados de un Estudio Prospectivo

Takeuchi T, Genovese MC, Haraoui B, Li Z, Xie L, Klar R, Pinto Correia A, Otawa S, Lopez-Romero P, de la Torre I, Rooney TP, Smolen JS.
Ann Rheum Dis. 2019 Feb;78(2):171-178. DOI 10.1136/annrheumdis-2018-213271

In active RA patients, with an inadequate response (IR) to DMARDs who achieve low disease activity (LDA) following baricitinib (BARI) 4 mg treatment, disease control is better maintained with continued BARI 4 mg compared to tapering to 2 mg. The objective of this study was to investigate the effect of BARI tapering in patients achieving sustained disease control with BARI 4 mg. In the long-term extension study RA-BEYOND, patients receiving BARI 4 mg who achieved sustained LDA or remission at two...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Igor Kos

Perfil de Seguridad de Baricitinib en Pacientes con Artritis Reumatoide Activa con más de 2 Años de Tiempo Mediano de Tratamiento

Smolen J, Genovese M, Takeuchi T, Hyslop D, Macias W, Rooney T, Chen L, Dickson C, Riddle Camp J, Cardillo T, Ishii T and Winthrop K.
J Rheumatol. 2019 Jan;46(1):7-18. DOI: 10.3899/jrheum.171361

Baricitinib (BARI) showed an acceptable 5.5-year safety profile in this integrated analysis of patients with moderate-to-severe, active RA. This study evaluated the safety profile of the oral, once daily Janus kinase inhibitor, BARI, in adults with moderately to severely active RA. Data from eight randomised clinical trials and one long-term extension study were pooled and analysed for placebo comparison and dose response. There were 3492 patients who received BARI for a total of 6637 patient-y...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Igor Kos

September 18

Progresión del Daño Estructural en Pacientes con Artritis Reumatoide Temprana Tratados con Metotrexato, Baricitinib, o Baricitinib más Metotrexato Basada en Respuesta Clínica del Estudio Fase 3 RA-BEGIN

van der Heijde D, Durez P, Schett G, Naredo E, Østergaard M, Meszros G, De Leonardis F, De La Torre I, López-Romero P, Schlichting D, Nantz E, Fleichmann R.
Clinical Rheumatology 2018;37:2381–90 DOI 10.1007/s10067-018-4221-0

Patients with active RA and little or no prior DMARD treatment, who achieved sustained clinical responses, were less likely to show structural damage progression, irrespective of treatment. RA-BEGIN was a 52-week double-blind, multicentre Phase 3 trial, which assessed the safety and efficacy of BARI as monotherapy or in combination with MTX versus MTX monotherapy, in RA patients with no or limited prior DMARDs use.1-4 This post-hoc analysis evaluated the structural damage progression in patients...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

Perfil de Lípidos y Efecto de Tratamiento con Estatinas en Agrupamiento de Estudios Fase II y Fase II de Baricitinib

Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB.
Ann Rheum Dis. 2018 Jul;77(7):988-995. DOI 10.1136/annrheumdis-2017-212461

Baricitinib (BARI) was associated with increased lipid levels; baseline statins did not alter these profiles. The introduction of statins during treatment reduced total cholesterol and LDL-C. The use of anti-inflammatory drugs in RA patients has been shown to alter lipid levels and is associated with reduced atherogenic risk. Increases in lipid levels, specifically HDL-C and LDL-C, have been observed in Phase 2 BARI studies1. This study analysed data from seven randomised RA Phase 2/3 studies o...

Keywords: JAK, Baricitinib, Real World, Cardiovascular

Translated by: Igor Kos

Respuesta Sostenida Siguiendo Discontinuación de Metotrexato en Pacientes con Artritis Reumatoide Tratados con Tocilizumab Subcutáneo

Kremer JM, Rigby W, Singer NG, Birchwood C, Gill D, Reiss W, Pei J, Michalska M.
Arthritis Rheumatol 2018;70:1200–08 DOI 10.1002/art.40493

The COMP-ACT study showed patients achieving low disease activity (LDA) with tocilizumab (TCZ) plus methotrexate (MTX) can discontinue MTX, while maintaining disease control for up to 16 weeks. Previous studies have shown TCZ to be efficacious as a monotherapy or in combination with MTX in patients with RA1,2. Patients frequently discontinue taking DMARDs, such as MTX, due to intolerance or adverse events. COMP-ACT is a randomised, double-blind, 52-week study evaluating the sustained efficacy of...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Igor Kos

Eficacia de la Monoterapia con Biológicos e Inhibidores JAK para el Tratamiento de Artritis Reumatoide Una Revisión Sistemática

Emery P, Pope JE, Kruger K, Lippe R, DeMasi R, Lula S, Kola B.
ADV Ther 2018; 35(10):1525–63 DOI: 10.1007/s12325-018-0757-2

The b/tsDMARDs evaluated in this systematic literature review (SLR) were shown to be efficacious as monotherapies, although combination therapies usually achieved better treatment outcomes. Current treatment guidelines recommend combining b/tsDMARDs with MTX in the treatment of RA; however, up to a third of patients are treated with monotherapy. While previous SLRs1–3 have compared the efficacy of b/tsDMARD mono- versus MTX combination therapy they covered a limited number of randomised co...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

August 18

Discontinuación de Tocilizumab después de lograr remisión en Pacientes con Artritis Reumatoide con Tratamiento con Tocilizumab Sólo o en Combinación con Metotrexate: Resultados de un Estudio Prospectivo Aleatorizado Controlado (el segundo año del estudio SURPRISE)

Kaneko Y, Kato M, Tanaka Y, Inoo M, Kobayashi-Haraoka H, Amano K, Miyata M, Murakawa Y, Yasuoka H, Hirata S, Tanaka E, Miyasaka N, Yamanaka H, Yamamoto K, Takeuchi T, the SURPRISE study group.
Ann Rheum Dis 2018; 77:1268–1275 DOI: 10.1093/rheumatology/key121

The second-year results from the SURPRISE study show that low disease activity (LDA) can be maintained after discontinuation of tocilizumab with continued methotrexate after remission is achieved. Discontinuation of biologic agents in patients who have achieved remission or low disease activity (LDA) is desirable from a risk–benefit point of view. Compared with TNF inhibitors, little is known regarding TCZ-free remission or LDA, but studies indicate that only a small proportion of patien...

Keywords: IL-6, Tocilizumab, Clinical, Efficacy

Translated by: Igor Kos

Dos Años de Sarilumab en Pacientes con Artritis Reumatoide y una Respuesta Inadecuada a MTX, Seguridad, Eficacia y Resultados Radiográficos

Genovese MC, van Adelsberg J, Fan C, Graham NMH, van Hoogstraten H, Parrino J, Mangan EK, Spindler A, Huizinga TWJ, van der Heijde D, for the EXTEND study investigators.
Rheumatology 2018;57:1423–1431 DOI: 10.1093/rheumatology/key121

Two-year treatment of active, moderate-to-severe RA with sarilumab, along with dose reduction in the event of laboratory abnormalities, resulted in durable efficacy outcomes and a safety profile consistent with previous reports involving IL-6R inhibition. Durable long-term safety and efficacy, reduced joint damage progression, and conserving health-related quality of life and work productivity are important goals of therapy in RA.1 Sarilumab significantly reduced disease activity, improved phy...

Keywords: IL-6, Sarilumab, Clinical, Safety

Translated by: Igor Kos

Eventos Adversos, Consideraciones Clinicas y Recomendaciones de Manejo en Pacientes con Artritis Reumatoide tratados con Inhibidores JAK

Atzeni F, Talotta R, Nucera V, Marino F, Gerratana E, Sangari D, Masala IF, Sarzi-Puttini P.
Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Janus kinase (JAK) inhibitors are efficacious in patients with moderate-to-severe RA and have a favourable safety profile. However adverse events (AE), in particular infections, are associated with the use of JAK inhibitors. This paper reviews the mechanism behind JAK inhibitors, the AEs associated with them, and provides consideration in the management of AEs in clinical practice. Data on two RA approved JAK inhibitors – tofacitinib (TOF) and baricitinib (BARI) – was obtained usin...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

July 18

Sarilumab para Pacientes Previamente Tratados con Artritis Reumatoide Moderada o Grave: La Perspectiva de un Grupo de Revisión de Evidencia de Evaluación de Tecnología Única de Nice

Bermejo I, Ren S, Simpson E, Clowes M, Scott DL, Young A, Stevenson M.
Pharmacoeconomics. 2018 Dec;36(12):1427-1437. doi: 10.1007/s40273-018-0677-7

In this National Institute for Health and Care (NICE) single technology appraisal of sarilumab (SAR) monotherapy and combination therapy with methotrexate (MTX), SAR was considered to have similar efficacy to other bDMARDs for treating moderate-to-severe RA with inadequate response to cDMARDs or TNFis. SAR was also considered a cost-effective use of National Health Service (NHS) resources versus some or all of its comparators in most considered populations. NICE is an independent organisation r...

Keywords: IL-6, Sarilumab, Clinical, Phase 3

Translated by: Igor Kos

Tromboembolismos con Inhibidores de Quinasa Janus (JAK) para Artritis Reumatoide: ¿Cuán real es el Riesgo?

Scott IC, Hider SL, Scott DL.
Drug Safety 2018 Jul;41(7):645–53

Current data suggests that JAK inhibitors may increase the risk of thromboembolism and pulmonary thrombosis (PT) in RA. Two JAK inhibitors – baricitinib (BARI) and tofacitinib (TOF) – are considered effective treatments for RA, however, there are concerns about the thromboembolic risks associated with them. In August 2017, the summary of product characteristics for BARI was revised to include a warning of developing DVT and pulmonary embolism (PE), with recommendations that BARI sho...

Keywords: JAK, Baricitinib, Clinical, Safety

Translated by: Igor Kos

Seguridad y Eficacia de Upadacitinib en Pacientes con Artritis Reumatoide Activa Refractaria a Fármacos Anti-Reumaticos Modificadores de la Enfermedad Biológicos (SELECT-BEYOND) un Ensayo Aleatorizado Controlado Fase 3

Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, Zhou Y, Mohamed M-EF, Meerwein S, Pangan AL.
Lancet 2018;391:2513–24

Upadacitinib (UPA) extended release formulation was effective in treating patients with moderate-to-severe RA with an inadequate response to bDMARDs. Phase 2 study data has shown that UPA is an efficacious and safe treatment for active RA.1,2 SELECT-BEYOND was a double-blind, long-term extension, Phase 3 study to assess the efficacy of UPA in patients with RA who were bDMARD-IR. The first 12-weeks of SELECT-BEYOND were placebo-controlled, with a double-blind period followed by an ongoing double...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Igor Kos

Seguridad y Eficacia de Upadacitinib en pacientes con Artritis Reumatoide con Respuesta Inadecuada a Fármacos Anti-Reumáticos Modificadores de la Enfermedad (SELECT-NEXT): un Ensayo Aleatorizado, Doble Ciego, Controlado-Placebo Fase 3

Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, Zhou Y, Othman AA, Pangan AL, Camp HS.
Lancet 2018;391:2503–12

Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo. In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3...

Keywords: JAK, Upadacitinib, Clinical, Phase 3

Translated by: Igor Kos

June 18

Características de los Pacientes influencian la elección de fármaco biológico en AR, y harán los biológicos no-TNFi aparentaren más nocivos que biológicos TNFi

Frisell T, Baecklund E, Bengtsson K, Giuseppe DD, Forsblad-d’Elia H, Askling J, on behalf of the ARTIS Study Group.
Ann Rheum Dis 2018; 77:650–57 DOI: 10.1136/annrheumdis-2017-212395

Analysis of patient characteristics revealed that older and less healthy patients with RA were more likely to receive non-TNFi bDMARDs as a first bDMARD compared to other treatments. This study aimed to describe patient characteristics at initiation of bDMARD treatment at two-time points: first bDMARD initiation and switch to second bDMARD after TNFi treatment. The second aim of the study was to estimate the potential of treatment channelling to confound results in comparative treatment studies...

Keywords: IL-6, Tocilizumab, Real World, Efficacy

Translated by: Igor Kos

Efectos de Baricitinib en Progresión Radiográfica de Daño Estructural en la Articulación en 1 año en Pacientes con Artritis Reumatoide y una Respuesta Inadecuada con Fármacos Modificadores de la Enfermedad Sintéticos Convencionales

van der Heijde D, Dougados M, Chen YC, Greenwald M, Drescher E, Klar R, Xie L, de la Torre I, Rooney TP, Witt SL, Schlichting DE, de Bono S, Emery P.
RMD Open. 2018 May 8;4(1):e000662. DOI: 10.1136/rmdopen-2018-000662

Once daily baricitinib (BARI) inhibited radiographic progression of structural joint damage in patients with an inadequate response or intolerance to csDMARDs over 48 weeks. Current treatment goals aim to use DMARDs to inhibit structural joint damage and prevent long-term functional disability. In RA-BUILD¹, BARI was shown to significantly reduce radiographic joint damage progression in patients with active RA, with an intolerance or inadequate response to csDMARDs. Here, the authors repor...

Keywords: JAK, Baricitinib, Clinical, Radiographic

Translated by: Igor Kos

Resultados Radiográficos de Largo Plazo y Resultados Informados por los Pacientes en pacientes con Artritis Reumatoide Tratados con Tofacitinib: Análisis Post-hoc de ORAL Start y ORAL Scan

Strand V, Kavanaugh A, Kivitz AJ, van der Heijde D, Kwok K, Akylbekova E, Soonasra A, Snyder M, Connell C, Bananis E, Smolen JS.
Rheumatol Ther. 2018 Dec;5(2):341-353. doi: 10.1007/s40744-018-0113-7

Tofacitinib (TOF) therapy reduced the progression of structural joint damage at 2 years, in patients of all disease states, compared with patients given methotrexate (MTX). Early intervention with DMARDs aim to prevent the development of future RA symptoms and inhibit the progression of structural damage to the joints. This post-hoc analysis uses data from two Phase 3 TOF studies, to examine the efficacy of early intervention with TOF on long-term radiographic outcomes and disease activity sta...

Keywords: JAK, Tofacitinib, Clinical, Radiographic

Translated by: Igor Kos

May 18

Farmacocinética de Upadacitinib con Regímenes Clínicos de Formulación de Liberación Extendida Utilizados en Ensayos Clínicos Fase 3 de Artritis Reumatoide

Mohamed MEF, Zeng J, Marroum PJ, Song IH, Othman AA.
Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462

Upadacitinib (UPA) extended release (ER) formulation dosing achieved the target profile that enables single dosing in patients with RA. In early clinical studies, UPA was given as an immediate release (IR) formulation, however patients were noted to experience fluctuations in blood plasma concentrations. To enhance patient compliance in UPA Phase 3 trials, ER tablets have been developed. Here, authors aimed at characterising the pharmacokinetics of UPA single and multiple doses of ER compared ...

Keywords: JAK, Upadacitinib, Preclinical, PK-PD

Análisis de los Reportes Espontáneos pos-Comercialización sometidos al FDA Sobre Eventos Adversos Tromboembólicos e Inhibidores JAK

Verden A, Dimbil M, Kyle R, Overstreet B, Hoffman KB.
Drug Saf 2018 Apr; 41(4):357–61 DOI: 10.1007/s40264-017-0622-2

Thromboembolic-related adverse events (AEs) were, in general, not considered a class-wide safety concern after analysis of tofacitinib (TOF) and ruxolitinib (RUX) clinical data, though pulmonary thrombosis is considered a potential class-wide safety issue and portal vein thrombosis was considered a potential safety issue for RUX. During analysis of baricitinib (BARI) clinical trial data, the FDA expressed concerns regarding thromboembolic events. Following this, the CHMP have recently added a ...

Keywords: JAK, Tofacitinib, Clinical, Safety

Tofacitinib en Artritis Reumatoide: Falta de Cambio Temprano en Actividad de la Enfermedad Predice una Baja Probabilidad de Lograr Baja Actividad de la Enfermedad en 6 meses

Van Vollenhoven RF, Lee EB, Fallon L, Zwillich SH, Wilkinson B, Chapman D, Demasi R, Keystone E.
Arthritis Care Res (Hoboken) 2019 Jan;71(1):71-79. DOI: 10.1002/acr.23585

This post-hoc analysis of two, Phase 3 studies, ORAL Start and ORAL Standard shows that early treatment response can predict long-term disease activity outcomes. EULAR recommendations suggest that treat-to-target strategies require regular target assessments with treatment approaches changed if targets are not reached at 6 months. To optimize this strategy, therapy outcomes should be known, and the relationship between short and long-term outcomes defined. The current analysis focused on the d...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Evaluación de la Actividad de la Enfermedad en Pacientes con Artritis Reumatoide Tratados con Tofactinib por RAPID3: Análisis Post Hoc de Dos Ensayos fase 3

Strand V, Lee EB, Yazici Y, Dikranian A, Wilkinson B, Takiya L, Zang C, Bananis E, Bergman MJ.
Clin Rheumatol 2018 Aug; 37(8):2043–53

Patients given tofacitinib (TOF) who achieved Routine Assessment of Patient Index Data 3 (RAPID3) remission or low disease activity (LDA) at 6 months, had improved long-term outcomes at 2 years, compared to patients with moderate or high disease activity (MDA/HDA) at 6 months. RAPID3¹ is a patient-reported evaluation of disease activity, based on pooled PROs; patient global assessment, patient assessment of arthritic pain and HAQ-DI scores. Previous studies with tocilizumab have suggested ...

Keywords: JAK, Tofacitinib, Clinical, PRO

April 18

Baricitinib para Artritis Reumatoide moderada o grave previamente tratada: Una perspectiva de un Grupo de Revisión de Evidencia de una Evaluación de Tecnología

Ren S, Bermejo I, Simpson E, Wong R, Scott DL, Young A, Stevenson M.
Pharmacoeconomics 2018 Jul; 36(7):769–78

In this National Institute for Health and Care (NICE) single technology appraisal of baricitinib (BARI) monotherapy and combination therapy with methotrexate (MTX), BARI efficacy was considered comparable to bDMARDs and a cost-effective use of National Health Service (NHS) resources. NICE is an independent organisation responsible for providing national guidance on health technologies in England. To be recommended by NICE, the company must provide evidence to prove BARI’s effectiveness, b...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Tofacitinib para el Tratamiento de Artritis Reumatoide después de Falla a Fármacos Antirreumáticos Modificadores de la Enfermedad: Una Perspectiva de un Grupo de Revisión de Evidencia de una Evaluación de Tecnología Única de NICE

Uttley L, Bermejo I, Shijie R, Martyn-St James M, Wong R, Scott DL, Young A, Stevenson M.
Pharmacoeconomics 2018 Sep; 36(9): 1063–72

In this National Institute for Health and Care (NICE) single technology appraisal of tofacitinib (TOF) plus methotrexate (MTX), TOF had similar efficacy and comparable costs to recommended bDMARDs plus MTX in patients with RA. NICE is an independent organisation responsible for providing national guidance on health technologies in England. To be recommended by NICE, the company must provide evidence to prove TOF’s effectiveness, both clinically and costly. This evidence based review, rep...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Efectividad y Seguridad de Tofacitinib en Artritis Reumatoide: Un Estudio de Cohorte

Machado MAÁ, Moura CS, Guerra SF, Curtis JR, Abrahamowicz M, Bernatsky S.
Arthritis Res Ther 2018; 20(1):60 doi: 10.1186/s13075-018-1539-6

A retrospective cohort study of tofacitinib (TOF) revealed that patients previously treated with methotrexate who initiated TOF, presented no differences in hospitalised infections or effectiveness, compared with non-TNF biologics. Currently, TOF is recommended in ACR and EULAR guidelines as an alternative to biologics after first-line cDMARD therapy. Previous indirect comparisons have shown that patients with RA who experience cDMARD failure show similar efficacy when given TNFis, abatacept, ...

Keywords: JAK, Tofacitinib, Real World, Safety

Efecto de Filgotinib, un inhibidor selectivo de JAK1, con o sin Metotrexate en pacientes con Artritis Reumatoide: Resultados Informados por los Pacientes

Genovese MC, Westhovens R, Meuleners L, van der Aa A, Harrison P, Tasset C, Kavanaugh A.
Arthritis Res Ther 2018; 20(1):57 doi: 10.1186/s13075-018-1541-z

Patient-reported outcomes (PROs) from two, Phase 2b, filgotinib (FIL) studies, DARWIN 1 and 2, revealed that patients receiving FIL had improved and sustained PRO responses compared with placebo. With suboptimal RA treatment, patients lose joint functional ability, which heavily influences patient quality of life. The previously reported data from the DARWIN studies, concluded that patients given FIL achieved clinically relevant dose-dependent improvements compared with patients given placebo&s...

Keywords: JAK, Filgotinib, Clinical, PRO

March 18

Experiencia Mundial de Vigilancia Después de la Comercialización de Tofacitinib en Artritis Reumatoide a lo largo de 3 Años

Cohen S, Curtis JE, DeMasi R, Chen Y, Fan H, Soonasra A, Fleischmann R.
Rheumatol Ther 2018 Jun; 5(1):283–91

This real-world analysis of tofacitinib (TOF) revealed that AEs reported by patients with RA from 2012 to 2015 were consistent with the known safety profile of TOF – no new safety risks were identified. As of August 2017, it is estimated that more than 102 000 patients worldwide have received TOF, but TOF safety has not been evaluated in patients with real-world experience. This analysis addressed this – by evaluating the safety of TOF from post-marketing surveillance (PMS) reports ...

Keywords: JAK, Tofacitinib, Real World, Safety

Translated by: Igor Kos

Efecto de Discontinuar o Empezar Metotrexate o Glucocorticoides en la Eficacia de Tofacitinib en Pacientes con Artritis Reumatoide: Un Análisis Post Hoc

Fleischmann R, Wollenhaupt J, Cohen S, Wang L, Fan H, Bandi V, Andrews J, Takiya L, Bananis E, Weinblatt ME.
Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration. This ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Igor Kos

Respuesta a Baricitinib Basado en Uso Previo de Biológicos en Pacientes con Artritis Refractaria

Genovese MC, Kremer JM, Kartman CE, Schlichting DE, Xie L, Carmack T, Pantojas C, Burston JS, Tony HP, Macias WL, Rooney TP, Smolen JS.
Rheumatology (Oxford) 2018 May; 57(5):900-908

Baricitinib (BARI) 2 or 4 mg had a beneficial treatment effect on patients with moderate to severe RA compared with placebo (PBO), irrespective of the number or nature of prior patient bDMARD use. The current therapeutic target for patients with established RA is low disease activity, but many patients fail to achieve this due to inadequate responses to DMARD therapies. With this patient population growing, therapies for these patients are considered one of the greatest unmet needs in RA. This...

Keywords: JAK, Baricitinib, Clinical, Efficacy

Translated by: Igor Kos

February 18

Daño Radiográfico Articular en Pacientes con Artritis Reumatoide Temprana: Comparación de Estrategias Treat-to-Target basadas en Tocilizumab y Metotrexate.

Teitsma X, Jacobs JWG, Welsing PMJ, Pethӧ-Schramm A, Borm MEA, van Laar JM, Lafeber FPJG, Bijlsma JWJ.
Rheumatology (Oxford) 2018; 57(2):309–17

Tocilizumab (TCZ) therapy in DMARD-naïve patients with RA, is more effective at reducing erosion progression, particularly in the feet, compared with treat-to-target methotrexate (MTX) therapy. This analysis looked at radiographic joint damage, including separate examination of erosion progression and joint space narrowing (JSN) in the hands and feet of patients enrolled in the U-Act-Early trial. Radiographic damage is a common symptom of RA, with treat-to-target strategies aimed at pre...

Keywords: IL-6, Tocilizumab, Clinical, Radiographic

Translated by: Igor Kos

Tofacitinib con Fármacos Modificadores de la Enfermedad Convencionales en Pacientes Chinos con Artritis Reumatoide: Resultados Informados por los Pacientes desde un Ensayo Fase 3 Controlado Aleatorizado

Li Z, An Y, Su H, Li H, Xu J, Zheng Y, Li G, Kwok K, Wang L, Wu Q.
Int J Rheum Dis 2018; 21(2):402–14

This Chinese sub-population of patients with RA from ORAL Sync reported significant improvements in patient-reported outcomes (PROs), which were maintained up to 12 months from tofacitinib (TOF) treatment initiation. ORAL Sync was a randomised, Phase 3 study investigating TOF therapy in combination with csDMARDs in patients with active RA who had previously had an inadequate response to csDMARDs. To date, this is the only Phase 3 study of TOF in patients from China with RA. This analysis inclu...

Keywords: JAK, Tofacitinib, Clinical, PRO

Translated by: Igor Kos

Reducir versus Mantener Metotrexate en concentración Estable en Combinación con Tocilizumab en Artritis Reumatoide: un Ensayo Aleatorizado, Doble Ciego.

Edwards CJ, Ӧstӧr AJK, Naisbett-Groet B, Kiely P.
Rheumatology (Oxford) 2018;57(1):84–91

Methotrexate (MTX) tapering in patients with active, severe RA receiving intravenous tocilizumab (TCZ) was non-inferior to continuing stable MTX doses in maintaining a good/moderate EULAR response. Although MTX and bDMARD combination therapy may produce better response rates than bDMARD monotherapy, one third of patients discontinue or are non-compliant with MTX due to preference or toxicity. This randomised, non-inferiority study investigated the efficacy and tolerability of MTX tapering and ...

Keywords: IL-6, Tocilizumab, Clinical, Phase 3

Translated by: Igor Kos

January 18

Tocilizumab Subcutáneo en Artritis Reumatoide: Resultados del Programa de Marco Común del Estudio Fase 4 TOZURA Conducido en 22 Países

Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Pethö-Schramm A.
Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. DOI: 10.1093/rheumatology/kex443

This multi-national TOZURA study programme confirmed the efficacy and safety profile of subcutaneous tocilizumab (TC-SC) when administered as either monotherapy or in combination with csDMARDs. TOZURA was a Phase 4 study programme that evaluated open-label, TCZ-SC in patients with moderate-to-severe RA. A total of 1804 patients with active RA were enrolled in the study programme. Patients had inadequate responses to csDMARDs, anti-TNF therapies, or they were MTX-naïve. TCZ-SC was administe...

Keywords: IL-6, Tocilizumab, Clinical, Phase 4

Translated by: Igor Kos

Eficacia y Seguridad de Tocilizumab Subcutáneo en Combinación con Fármacos Antirreumáticos Modificadores de la Enfermedad a lo largo de 2 años Incluyendo Escalamiento para Dosis Semanal en Artritis Reumatoide

Kivitz A, Olech E, Borofsky MA, Zazueta B, Navarro-Sarabia F, Radominski SC, Merrill JT, Pacheco-Tena C, Pei J, Nasmyth-Miller, Pope JE.
J Rheumatol 2018 Apr; 45(4):456-464

This 2-year Phase 3 study, proved that subcutaneous tocilizumab (TC-SC) has long-term efficacy and an acceptable safety profile. Patients enrolled had been previously diagnosed with RA with an inadequate response to DMARDs. Patients were randomised 2:1 to receive doses of TCZ-SC (n=437) or PBO (n=219) every other week for 6 months. After this time, all patients received TCZ-SC. Escape therapy, defined as weekly TCZ-SC, was available to patients from Month 3. Efficacy was analysed using ACR resp...

Keywords: IL-6, Tocilizumab, Clinical, Phase 3

Translated by: Igor Kos

Resultados Informados por los Pacientes con Artritis Reumatoide con Diagnostico Novo y Temprano con Estrategia de Tratamiento “Treat-to-Target” -Tocilizumab o Metotrexate-

Teitsma XM, Jacobs JWG, Welsing PMJ, Pethö-Schramm A, Borm MEA, Hendriks L, Denissen NHAM, van Laar JM, Lafeber FPJG, Bijlsma JWJ.
Rheumatology (Oxford) 2017 Dec 1;56(12):2179-2189 doi: 10.1093/rheumatology/kex319

Patient-reported outcomes (PROs) vastly improved in the first 24 weeks post-initiation of tocilizumab (TCZ) therapies compared to methotrexate (MTX) monotherapy in the U-Act-Early trial. U-Act-Early was a two-year, treat-to-target study that compared the safety and efficacy of TCZ and MTX treatment strategies in DMARD-naïve patients with early RA. Sustained remission was classed as more effective in patients given TCZ monotherapy or combination therapy with MTX compared to MTX alone. TCZ th...

Keywords: IL-6, Tocilizumab, Clinical, PRO

Translated by: Igor Kos

December 17

Efectividad a largo plazo de Tocilizumab en pacientes con Artritis Reumatoide, estratificados por número de Fracasos de Tratamiento con Agentes Biológicos: Resultados del estudio de cohorte Germánico RABBIT

Baganz L, Richter A, Kekow J, Bussmann A, Krause A, Stille C, Listing J, Zink A, Strangfeld A.
Rheumatol Int 2018 Apr; 38(4):579-87

In this observational study, the German RABBIT cohort was used to assess the long-term effectiveness and retention rates of tocilizumab (TCZ) in patients with prior bDMARD failures. Results of the study suggested that TCZ could be an effective treatment option for patients with difficult-to-treat RA. A total of 885 patients were involved in the study and these were categorised dependent on the number of bDMARD failures they had prior to TCZ treatment. Patient data recorded in the cohort include...

Keywords: IL-6, Tocilizumab, Real World, Efficacy

Translated by: Igor Kos

Efecto de Glucocorticoides en la eficacia Clínica y Radiográfica de Tofacitinib en Pacientes con Artritis Reumatoide: Un análisis Posthoc de datos desde 6 estudios fase III

Charles-Schoeman C, van der Heijde D, Bumester GR, Nash P, Zerbini CAF, Connell CA, Fan H, Kwok K, Bananis E, Fleischmann R.
J Rheumatol 2018 Feb; 45(2):177-87

In this post hoc analysis, six Phase 3 studies were used to analyse the effect of glucocorticoids (GC) on the efficacy of tofacitinib (TOF) in patients with RA. Concomitant use of GC did not affect the clinical or radiographic outcomes of patients treated with TOF. Data from all six clinical trials were evaluated, with four studies (ORAL Scan, ORAL Standard, ORAL Sync and ORAL Step) being pooled for analysis. In these studies, MTX was used as a comparison and patients were required to maintain ...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Igor Kos

Inhibición de JAK como una estrategia terapéutica para Enfermedades Inmunes e Inflamatorias

Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ.
Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions. First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Igor Kos

Tratamiento Bien Sucedido de Artritis Inducida por Inhibidores de Checkpoint con Tocilizumab: Una Serie de Casos

Kim ST, Tayar J, Trinh VA, Suarez-Almazor M, Garcia S, Hwu P, Johnson DH, Uemura M, Diab A.
Ann Rheum Dis 2017;76:2061-64. doi: 10.1136/annrheumdis-2017-211560

This case series evaluated the use of tocilizumab (TCZ) as an effective treatment for patients who develop arthritis as an adverse event (AE) of immune checkpoint inhibitor (ICI) cancer treatment. Results suggested that TCZ was an effective treatment, as it reduced the arthritis disease progression. ICIs have been defined as a revolutionary treatment for metastatic melanomas; however, a common AE is the development of polyarthritis. Current arthritis treatments reduce the efficiency of ICI thera...

Keywords: IL-6, Tocilizumab, Clinical, PRO

Translated by: Igor Kos

Terapia con Tofacitinib para Artritis Reumatoide: Un Estudio de Comparación Directa entre Pacientes experimentados y vírgenes de tratamiento biológico

Mori S, Yoshitama T, Ueki Y.
Intern Med. 2018 Mar 1;57(5):663-670. doi: 10.2169/internalmedicine.9341-17

This 6-month prospective direct comparison study analysed the effectiveness of tofacitinib (TOF) therapy on bDMARD-naïve and bDMARD-experienced patients. bDMARD-naïve patients were more responsive to TOF therapy than bDMARD-experienced patients. The study analysed the data of 113 patients diagnosed with high or moderate disease activity, defined using CDAI scores. All patients had failed to achieve CDAI low disease activity or remission with MTX therapy for ≥3 months. Patients were...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Igor Kos

November 17

Herpes Zoster y Tofacitinib: Resultados Clínicos y Riesgo de Terapia Concomitante

Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, Hirose T, Nduaka CI, Wang L, Mendelsohn AM, Fan H, Chen C, Bananis E.
Arthritis Rheumatol 2017;69(10):1960–68

The results of this analysis of patients with herpes zoster (HZ) within the global tofacitinib (TOF) RA programme suggest that there is likely to be a greater HZ risk in patients receiving TOF and glucocorticoids compared with patients receiving TOF monotherapy. The global TOF RA development programme comprised 2 Phase 1, 9 Phase 2, 6 Phase 3 and 2 long-term extension studies. These studies included 6192 patients; data were reviewed to identify cases of HZ. Crude incidence rates of number of pa...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

Tofacitinib o Adalimumab versus Placebo para Artritis Psoriásica

Mease P, Hall S, FitzGerald O, van der Heijde D, Merola J F, Avila-Zapata F, Cieslak D, Graham D, Wang C, Menon S, Hendrikx T, Kanik K S.
N Engl J Med 2017; 377:1537-50. DOI: 10.1056/NEJMoa1615975

In the Phase 3 OPAL Broaden trial of patients with active psoriatic arthritis (PsA) with inadequate response to ≥1 csDMARD, superior efficacy was observed in patients treated with tofacitinib (TOF) compared with those given placebo. Patients were randomised to: 5 mg TOF BID, 10 mg TOF BID, 40 mg adalimumab administered subcutaneously q2W, or placebo with a switch to 5 mg TOF at Month 3. Adalimumab was used as an active control in the study. A variety of primary and secondary endpoints wer...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Igor Kos

Tofacitinib para Pacientes con Artritis Psoriásica con respuesta Inadecuada a Inhibidores de TNF

Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, Kudlacz E, Wang C, Menon S, Hendrikx T, Kanik KS.
N Engl J Med 2017;377:1525–36.

The study data presented that tofacitinib (TOF) improves efficacy response rates in patients with severe psoriatic arthritis (PsA) who have an inadequate response to TNF inhibitors. The Phase 3 Oral Psoriatic Arthritis Trial (OPAL) Beyond study evaluated patients with active PsA who had inadequate responses to more than one TNFi. Patients were randomised 2:2:1:1 to 5 mg TOF BID or 10 mg TOF BID for 6 months; or PBO, with a switch to 5 mg TOF BID or to 10 mg BID at 3 months. Primary endpoints w...

Keywords: JAK, Tofacitinib, Clinical, Phase 3

Translated by: Igor Kos

Eficacia y Seguridad de Baricitinib en Pacientes Ancianos con Artritis Reumatoide

Fleischmann R, Alam J, Arora V, Bradley J, Schlichting DE, Muram D, Smolen JS.
RMD Open. 2017; 3(2): e000546. doi: 10.1136/rmdopen-2017-000546

In this post hoc analysis of pooled data from two randomised controlled trials, RA-BUILD and RA-BEAM, age was shown not to be a contraindication for use of baricitinib. Patients in RA-BUILD were csDMARD-inadequate responder(IR) patients who received an oral placebo or 2 mg or 4 mg baricitinib once daily. Patients in RA-BEAM were MTX-IR patients and received an oral placebo, 4 mg baricitinib once daily or subcutaneous adalimumab every 2 weeks. Efficacy and safety of baricitinib in elderly patie...

Keywords: JAK, Baricitinib, Clinical, Phase 3

Translated by: Igor Kos

Persistencia en el tratamiento y Costos con Atención Médica entre Pacientes con Artritis Reumatoide Cambiando Biológicos en los Estados Unidos

Chastek B, Chieh-I Chen, Proudfoot C, Shinde S, Kuznik A, Wei W.
Adv Ther. 2017 Nov;34(11):2422-2435. doi: 10.1007/s12325-017-0617-5

Updated treatment guidelines recommend the use of different mechanism of action (MOA) therapies earlier in the treatment course. Clinical studies have revealed that this approach may be better than TNFi cycling, and may be more cost effective. This study of Commercial and Medicare Advantage claims data showed that patients who switched MOA had higher treatment persistence and lower healthcare costs than TNFi cyclers. After the first TNFi claim, patients either cycled to another TNFi (n=935) or...

Keywords: JAK, Tofacitinib, Real World, Value

Translated by: Igor Kos

October 17

Impacto de Tocilizumab Monoterapia en los Resultados Informados por los Pacientes (PROs) con Artritis Reumatoide de dos Ensayos Controlados Aleatorizados

Strand V, Michalska M, Birchwood C, Pei J, Tuckwell K, Finch R, Gabay C, Kavanaugh A, Jones G.
RMD Open;3:e000496. doi: 10.1136/rmdopen-2017-000496

This post hoc analysis of 2 randomised controlled trials (RCTs) AMBITION and ADACTA found that tocilizumab monotherapy results in substantial and clinically meaningful improvements in patient-reported outcomes (PROs) over 24 weeks. PROs assessed included patient global assessment (PtGA), pain, HAQ-DI, Functional Assessment of Chronic Illness Therapy (FACIT-F) and Short-Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores. Tocilizumab (TCZ)...

Keywords: IL-6, Tocilizumab, Clinical, PRO

Translated by: Igor Kos

Resultados Informados por los Pacientes (PROs) de Baricitinib en Pacientes con Artritis Reumatoide sin tratamiento o con tratamiento previo limitado con fármacos antirreumáticos modificadores de la enfermedad

Schiff M, Takeuchi T, Fleischmann R, Gaich CL, DeLozier AM, Schlichting D, Kuo W, Won J, Carmack T, Rooney T, Durez P, Shaikh S, Hidalgo RP, van Vollenhoven R, Zerbini C.
Arthritis Res Ther. 2017 Sep 18;19(1):208

RA-BEGIN was a Phase 3, double-blind randomised active comparator-controlled study to evaluate baricitinib as monotherapy or in combination with MTX in patients with active RA who were naïve to csDMARDS and bDMARDS. In this analysis of the RA-BEGIN study, baricitinib alone or with MTX when used as initial therapy resulted in significant improvements in most patient-reported outcome measures compared with MTX. At baseline, study participants had active RA, impaired physical function, mode...

Keywords: JAK, Baricitinib, Clinical, PRO

Translated by: Igor Kos

Linfoma en el Programa Clínico de Desarrollo de Tofacitinib en Artritis Reumatoide

Mariette X, Chen C, Biswas P, Kwok K, Boy MG.
Arthritis Care Res (Hoboken). 2018 May;70(5):685-694. doi: 10.1002/acr.23421

Analysis of 19 studies involving the use of tofacitinib to treat RA showed that lymphoma incidence rate and type were consistent with expectations in the RA population as a whole, and did not increase with tofacitinib exposure time. Previous research has suggested that there is a link between the likelihood of developing malignant tumours and RA. Previously, it has been unclear whether the increased rates seen are due to the use of immunomodulatory therapies, such as tofacitinib, which are used...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

Niveles de transaminasas y Eventos Hepáticos Durante Tratamiento con Tocilizumab: Análisis Conjunta de Datos de Seguridad en Ensayos Clínicos de Largo Plazo en Artritis Reumatoide.

Genovese MC, Kremer JM, van Vollenhoven RF, Alten R, Scali JJ, Kelman A, Dimonaco S, Brockwell L.
Arthritis Rheumatol. 2017 Sep;69(9):1751-1761. doi: 10.1002/art.40176

In this pooled analysis investigating liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab (TCZ) treatment for RA in clinical trials, although transaminase elevations were frequent, rates of hepatic serious AEs remained low. Data were pooled from patients who received ≥1 dose of IV TCZ with or without DMARDs in Phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study. A total of 4171 patients were included in the all-exposure populati...

Keywords: IL-6, Tocilizumab, Clinical, Safety

Translated by: Igor Kos

September 17

Seguridad E Inmunogenicidad de la Vacunación Para Herpes Zoster en Pacientes con Artritis Reumatoide Antes de Empezar Tofacitinib: Un Ensayo Aleatorizado Fase II

Winthrop KL, Wouters A, Choy E, Soma K, Hodge J, Nduaka C, Biswas P, Needle E, Passador MS, Mojcik C, Rigby W.
Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187

Patients with RA who started treatment with tofacitinib 2–3 weeks after being vaccinated against herpes zoster had similar varicella zoster virus (VZV)-specific humoral and cell-mediated responses to the live vaccine compared to patients who received placebo. In this Phase 2 study, humoral and cell-mediated immune responses were evaluated before receipt of live zoster vaccine (LZV) and at 2, 6 and 14 weeks after vaccination, having been randomised to tofacitinib 5 mg BID or placebo, 2&nda...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

Herpes Zoster y Tofacitinib en Pacientes con Artritis Reumatoide

Winthrop KL, Yamanaka H, Valdez H, Mortensen E, Chew R, Krishnaswami S, Kawabata T, Riese R.
Arthritis Rheumatol 2014;66:2675–84

Patients who were treated with tofacitinib in the RA clinical development programme were more likely to develop herpes zoster than were those who received placebo. Cases of herpes zoster reported by investigators in the Phase 2, Phase 3 and long-term extension studies of tofacitinib were evaluated. Herpes zoster was noted in 5% of tofacitinib-treated patients; only 7% of these cases were serious, no patients with herpes zoster died and only 10% permanently discontinued tofacitinib treatment. T...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

Resultados Informados por los Pacientes (PROs) desde un Estudio Fase 3 de Baricitinib contra Placebo o Adalimumab en Artritis Reumatoide: Análisis secundario del estudio RA-BEAM

Keystone EC, Taylor PC, Tanaka Y, Gaich C, DeLozier AM, Dudek A, Velasco Zamora J, Covarrubias Cobos JA, Rooney T, de Bono S, Arora V, Linetzky B, Weinblatt ME.
Ann Rheum Dis 2017;76(11):1853-1861. doi: 10.1136/annrheumdis-2017-211259

This paper describes the patient-reported outcome (PRO) data collected in RA-BEAM, a Phase 3 study of baricitinib compared with both placebo and adalimumab in patients with RA and an inadequate response to MTX. PRO measures evaluated include health-related quality of life (HRQOL), physical function, disability, fatigue, sleep, mental health status, work productivity and work activity impairment. The RA-BEAM study demonstrated that patients treated with baricitinib experienced a greater impro...

Keywords: JAK, Baricitinib, Clinical, PRO

Translated by: Igor Kos

Eficacia y Seguridad de Baricitinib a través de 128 semanas en un estudio abierto, de extensión a largo plazo en pacientes con Artritis Reumatoide

Keystone EC, Genovese MC, Schlichting DE, de la Torre I, Beattie SD, Rooney TP, Taylor PC.
J Rheumatol. 2018 Jan;45(1):14-21. doi: 10.3899/jrheum.161161

This open-label extension (OLE) of a Phase 2b randomised controlled trial (RCT) found that safety data collected over 2 years of treatment were generally consistent with previous findings for baricitinib in RA. In the RCT, baricitinib demonstrated significant improvement in disease activity compared with placebo and an acceptable safety profile in patients with RA and an inadequate response to MTX. Patients who completed the 24-week double-blind period of the study were eligible for the OLE. Ra...

Keywords: JAK, Baricitinib, Clinical, Phase 2

Translated by: Igor Kos

August 17

Evaluation of Newly Proposed Remission Cut-points for Disease Activity Score in 28 Joints (DAS28) in Rheumatoid Arthritis upon IL-6 Pathway Inhibition

Schoels M, Alasti F, Smolen JS and Aletaha D.
Arthritis Res Ther. 2017 Jul 4;19(1):155. doi: 10.1186/s13075-017-1346-5

DAS28 is not currently included in the joint remission definitions of the ACR and the EULAR because its formula is disproportionately influenced by Acute Phase Response (APR). IL-6 pathway blockers or JAK inhibitors greatly reduce APR, causing patients to be classed as in DAS28 remission despite still having multiple swollen joints. To make DAS28 remission criteria more stringent, the alternative cut-points of <1.9 and <2.2 for CRP and ESR, respectively, have been proposed. This study q...

A Comparison of Discontinuation Rates of Tofacitinib and Biologic Disease-modifying Anti-rheumatic Drugs in Rheumatoid Arthritis: a Systematic Review and Bayseian Network Meta-analysis Regression

Park JS-K, Lee MY, Jang E-J, Kim H-L, Ha D-M, Lee E-K.
Clin Exp Rheumatol 2017;35:689–99

Based on a Bayesian network meta-analysis (NMA) in patients with RA who previously showed failure with csDMARDs or biologics, discontinuation rates between tofacitinib (TOF) and biologics (TNFis, abatacept [ABT], rituximab [RTX] and tocilizumab [TCZ]) differed based on previous treatments and reasons for discontinuation. Data were collected from randomised controlled trials (RCT) found from literature searches from the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE. Discon...

Treatment Persistence and Clinical Outcomes of Tumor Necrosis Factor Inhibitor Cycling or Switching to a New Mechanism of Action Therapy: Real-world Observational Study of Rheumatoid Arthritis Patients in the United States with Prior Tumor Necrosis Factor Inhibitor Therapy

Wei W, Knapp K, Wang L, Chen C-I, Craig GL, Ferguson K Schwartzman S.
Adv Ther. 2017 Aug;34(8):1936-1952. doi: 10.1007/s12325-017-0578-8

This retrospective, observational study used a real-world US clinical database to demonstrate greater effectiveness of switching to a therapy with an alternative mechanism of action (MOA) vs cycling between TNF inhibitors (TNFis) in patients in which TNFi therapy has failed. Between 1 April 2010 and 31 March 2015, a total of 613 of the observed patients failed a TNFi therapy and then either cycled to another TNFi therapy (54.2%) or switched to a therapy with an alternative MOA (45.8%). The most...

Análisis del cáncer de piel no melanoma a través del programa clínico de Tofacitinib en la Artritis Reumatoide

Curtis JR, Lee EB, Martin G, Mariette X, Terry TT, Chen Y, Geier J, Andrews J, Kaur M, Fan H, Nduaka CI.
Clin Exp Rheumatol 2017;35:614–22

Because non-melanoma skin cancer (NMSC) is one of the most common malignancies associated with RA immunomodulatory therapies, this analysis looked to determine the rate of NMSC incidence per 100 patient-years in patients with RA receiving TOF in the clinical trial programme. The Phase 1, 2, and 3 IRs (combined) for both TOF 5- and 10 mg were low and comparable to those of adalimumab, MTX and placebo, IRs remained stable over time. TOF doses used in the 2 Phase 1; 8 Phase 2; and 6 Phase 3 studi...

Keywords: JAK, Tofacitinib, Clinical, Safety

Translated by: Igor Kos

July 17