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...

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

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

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

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

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

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

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

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

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

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

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...

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

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

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

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

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

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

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

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

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...

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-modifying Antirheumatic Drugs: 2016 Update

EULAR RA Management Task Force Smolen J, Landewé R, Bijlsma J, et al.
Ann Rheum Dis Published Online First: 06March2017. doi:10.1136/annrheumdis-2016-210715

The EULAR 2016 recommendations update, based on three systematic literature reviews (SLRs) and expert opinion, comprises four overarching principles and 12 recommendations compared with 14, respectively, in 2013. These recommendations intend to inform regarding EULAR’s most recent consensus on the management of RA, with the aim of attaining the best outcomes with current therapies. All DMARD types: csDMARDs, bDMARDs, tsDMARD and bsDMARD are addressed, and cost aspects are taken into consi...

Baricitinib in Patients with Inadequate Response or Intolerance to Conventional Synthetic DMARDs: Results from the RA-BUILD Study

Dougados M, van der Heijde D, Chen Y-C, Greenwald M, Drescher E, Liu J, Beattie S, Witt S, de la Torre I, Gaich C, Rooney T, Schlichting D, de Bono S, Emery P.
Ann Rheum Dis 2017;76:88–95.

Baricitinib improved symptoms of RA in the RA-BUILD trial, a Phase 3 study of baricitinib in patients with moderately to severely active RA, refractory to or intolerant to csDMARDs. As well as providing a short-term (24 weeks) benefit, there appeared to be joint damage benefit, considered a marker of long-term disability. RA-BUILD was a 24-week randomised, double-blind, placebo-controlled parallel-group study. Patients were randomised 1:1:1 to receive once-daily doses of placebo (n=228) or bari...

Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase 2b Study in Patients with Active Rheumatoid Arthritis

Kremer J, Genovese MC, Keystone E, Taylor PC, Zuckerman SH, Ruotolo G, Schlichting DE, Crotzer VL, Nantz E, Beattie SD and Macias WL.
Arthritis Rheumatol 2017. DOI 10.1002/art.40036.

In this analysis of the effect of baricitinib on changes in lipid profile, lipoprotein particle size and apolipoprotein content, increases in serum lipids were observed with HDL-C increases correlating with improved clinical outcomes. Eligible patients (N=301) met the inclusion criteria for the Phase 2b randomised, double-blind, placebo-controlled study.1 Patients were assigned in a 2:1:1:1:1 ratio to once-daily doses of placebo or baricitinib 1, 2, 4, or 8 mg, respectively. Those receiving 2 m...

Baricitinib, Methotrexate, or Combination in Patients with Rheumatoid Arthritis and no or Limited Prior Disease-Modifying Antirheumatic Drug Treatment

Fleischmann F, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, Zerbini CAF, Gurbuz S, Dickson C, de Bono S, Schlichting D, Beattie S, Kuo W-L, Rooney T, Macias W, Takeuchi T.
Arthritis Rheumatol 2016. DOI 10.1002/art.39953. Accepted article

In this 52-week study of patients receiving initial therapy for RA, baricitinib alone or in combination with MTX demonstrated superior efficacy compared with MTX alone. Patients naïve to csDMARD (no or <3 doses of MTX) or bDMARD were randomised 4:3:4 (N=588) to MTX QW, baricitinib 4 mg QD or baricitinib 4 mg QD + MTX QW. The primary endpoint assessment was noninferiority of baricitinib monotherapy to MTX based on ACR20 response at Week 24. Not only was the primary endpoint met, baricit...

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

Tanaka Y, Emoto K, Cai Z, et al.
J Rheumatol. 2016;43(3):504–511.

Clinical trials have shown baricitinib once daily to be effective in patients with RA. However, this Janus kinase (JAK) 1/JAK2 inhibitor has not been evaluated in a Japanese population. In this 12-week, placebo-controlled study, 145 Japanese patients were enrolled and received placebo, 1 mg, 2 mg, 4 mg or 8 mg oral baricitinib daily. Efficacy results were encouraging and consistent with earlier trials. Significantly more baricitinib patients achieved ACR20 response at Week 12 of treatment compa...

Baricitinib in Patients with Refractory Rheumatoid Arthritis

Genovese et al.
N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247

For patients who have an inadequate response or unacceptable side effects associated with biologic DMARDs, the options for treatment beyond conventional DMARDs are limited. This phase 3 trial of the JAK 1/2 inhibitor, baricitinib, studied its efficacy in bDMARD-IR patients. 527 patients were randomized to either baricitinib 2mg, 4mg or placebo for up to 24 weeks. At week 12 the primary endpoints were tested hierarchically to control type 1 error; these endpoints were ACR20, HAQ-DI score, DAS28...

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers

Shi JG, Chen X, Lee F, Emm T, Scherle PA, Lo Y, Punwani N, Williams WV, Yeleswaram S.
Mod J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.

Current biologic therapies for RA, such as biologic cytokine inhibitors, which selectively target inflammatory molecules with an exquisite degree of specificity, are not clinically effective in all patients with rheumatoid arthritis. As such, there remains an unmet clinical need for more effective and better tolerated therapies. Baricitinib (LY3009104, also previously known as INCB028050) is a potent and selective small molecule inhibitor of JAK1/2, which play an important role in cytokine signa...

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, Lee CH, Fidelus-Gort RK, Luchi ME, Rooney TP, Macias WL, Genovese MC.
Ann Rheum Dis. 2015;74(2):333–340

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies. This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitinib, fo...

Propuesta para una nueva nomenclatura de medicamentos antirreumáticos modificadores de la enfermedad

Smolen JS et al.
Ann Rheum Dis 2013. doi: 10.1136/annrhuemdis-2013-204317

With the recent emergence of new therapeutics for rheumatoid arthritis, new nomenclature for disease-modifying antirheumatic drugs (DMARDs) may be needed to more accurately describe the new agents. Currently, DMARDs are divided into two broad groups: synthetic DMARDs (sDMARDs) and biological DMARDs (bDMARDs). The authors propose dividing synthetic DMARDs into conventional synthetic DMARDs (csDMARDs) which would encompass traditional DMARDs (e.g. methotrexate, leflunomide), and targeted synthetic...

Keywords: Cytokine Signalling

La inhibición selectiva de las JAK1 y JAK2 es eficaz en modelos de artritis en roedores: caracterización preclínica de INCB028050

Fridman JS, Scherle PA, Collins R, et al.
Journal of Immunology 2010; 184(9):5298-307

This preclinical characterisation study examined the efficacy and tolerability of the small molecule INCB028050 (now known as baricitinib), an orally bioavailable, selective Janus kinase (JAK) 1/JAK2 inhibitor, in rodent models of arthritis. The decision to investigate its effects of INCB028050 followed positive evidence for the related compound ruxolitinib, the JAK inhibitor tofacitinib and the IL-6 inhibitor tocilizumab in rheumatoid arthritis (RA). In this preclinical study, INCB028050 was sh...

Keywords: JAK, Baricitinib, Preclinical, Selectivity