Cytokine Signalling Forum

Publications





January 22

Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment

Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR.
Rheumatol Ther. 2021. Epub ahead of print. doi: 10.1007/s40744-021-00390-0

This post hoc analysis provides the first detailed description of the management and outcomes of HZ events in tofacitinib RA and PsA clinical studies. While prior studies have characterised the increased HZ risk with JAKinibs, the clinical management of these events has not been detailed. To this end, Winthrop, et al. analysed data from 21 RA and 3 PsA clinical studies to evaluate how HZ events and their sequelae were clinically managed during the RA and PsA tofacitinib clinical development pr...

Pain Reduction in Rheumatoid Arthritis Patients Who Use Opioids: A Post Hoc Analysis of Phase 3 Trials of Baricitinib

Pope JE, Lee YC, Curtis JR, Mo D, Xie L, Dickson CL, Schlichting DE, Cardoso A, Simon LS, Taylor PC.
ACR Open Rheumatol. 2021. Epub ahead of print. doi: 10.1002/acr2.11380

This post hoc analysis shows that pain reduction was similar between opioid users and nonusers with baricitinib 2 mg and 4 mg, but not adalimumab. Use of opioids to treat RA-related pain has increased, yet long-term use has been associated with reduced efficacy and safety concerns. In addition, the misuse of opioids has resulted in a public health crisis in the United States and highlights the need for safe, effective nonaddictive alternatives for pain management. As such, Pope, et al. assessed...

November 21

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Winthrop KL, Nash P, Yamaoka K, Mysler E, Khan N, Camp HS, Song Y, Suboticki JL, Curtis JR.
Ann Rheum Dis. 2021. Epub ahead of print. doi: 10.1136/annrheumdis-2021-220822.

JAKinibs have been linked with an increased risk of HZ in patients with RA. To this end, Winthrop, et al. evaluated data from six Phase III clinical trials to determine the incidence of HZ in the upadacitinib (UPA)-treated patients with RA and identify potential risk factors for the development of HZ in these patients. Analysis of data provides further support for the need for continued vigilance and monitoring for signs of herpes zoster (HZ) in patients receiving UPA, particularly in Asian popu...

March 21

Qual Resultado Relatado pelo Paciente é o mais Importante para os Pacientes Reumatológicos para ser Rastreado Digitalmente? Um Estudo 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

Sinalização JAK/STAT induzida por Citoquinas está Associada com Artrite Reumatoide e Atividade da Doença

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

September 20

Incidência de Eventos Tromboembólicos Arteriais e Venosos Reportados nos Programas de Desenvolvimento de Tofacitinib em Artrite Reumatoide, Psoríase e Artrite Psoriática e de Dados 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

May 20

Análise Integrada de Segurança de Tofacitinib em Artrite Psoriásica em Estudos de Fase 3 e de Extensão a Longo Prazo e Comparação com Dados Observacionais 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

May 19

Segurança e Eficácia de Tofacitinib por até 9.5 Anos no Tratamento de Artrite Reumatoide: Resultados Finais de um Estudo de Extensão Global Aberto

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 ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

Translated by: Igor

November 18

Herpes zoster in Tofacitinib: Risk is Further Increased with Glucocorticoids but not Methotrexate

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 ...

April 18

Effectiveness and Safety of Tofacitinib in Rheumatoid Arthritis: a Cohort Study

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, ...

November 17

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

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...

August 17

Analysis of Non-melanoma Skin Cancer across the Tofacitinib Rheumatoid Arthritis Clinical Programme

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...

July 17

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Cohen BS, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Shoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J.
Ann Rheum Dis 2017;76:1253-1262. DOI 10.1136/annrheumdis-2016-210457

This analysis of exposure to tofacitinib, an oral JAKi for the treatment of RA, for up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. Adverse events were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports. Data were collated into an integrated safety summary of tofacitinib in adult patients with active RA, and included data spanning the tofacitinib clinical programme: from 2 P...

June 17

Outcomes of Tumor Necrosis Factor Inhibitor Cycling versus Switching to a Disease-modifying Anti-rheumatic Drug with a New Mechanism of Action Among Patients with Rheumatoid Arthritis

Chastek B, Becker LK, Chen CI, Mahajan P and Curtis JR.
J Med Econ 2017;20:464–73

This retrospective study looked at claims-based datasets to establish whether it is preferable to switch to another TNF inhibitor (TNFi) or to a therapy with a different mechanism of action (MOA) when RA treatment failure occurs with an initial TNFi, due to inadequate response or lack of tolerability. Administrative claims data from a large US database were used to compare treatment patterns, treatment effectiveness (based on fulfillment of six criteria) and costs in in the 12 months after RA p...

March 17

Efficacy and Safety of Tofacitinib in Older and Younger Patients with Rheumatoid Arthritis

Curtis JR, Schulze-Koops H, Takiya L, Mebus CA, Terry KK, Biswas P and Jones TV.
Clin Exp Rheumatol 2017 Jan 4

In this analysis of patients with moderate to severe RA treated with tofacitinib (TOF) in Phase 3 and long-term extension (LTE) studies, patients aged 65 years had similar efficacy and a numerically higher risk of SAEs and discontinuations due to AEs compared with younger patients. The Phase 3 population included patients from five trials (n=3111) of TOF 5 mg or 10 mg BID or placebo. The LTE population (n=4102) included patients from two studies who had participated in Phase 1, 2 or 3 TOF stud...

December 15

Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study

Curtis JR, Sarsour K, Napalkov P, Costa LA, and Schulman KL.
Arthritis Research & Therapy (2015) 17:319 DOI: 10.1186/s13075-015-0835-7

Interstitial lung disease (ILD) is a common extra-articular condition for RA patients. This retrospective cohort study of health insurance databases investigates the ILD incidence and exacerbation between ABA, TCZ, RTX, and anti-TNFα agents in adult RA patients with prior biologic therapy. Two definitions of ILD were used: one specific, one sensitive; descriptive results were produced for both. In patients with no history of ILD, the overall incidence rate of ILD ranged from 1.8% to 6.4%...

May 15

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, Soma K, Wang L, Riese R.
Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-205847. doi: 10.1136/annrheumdis-2014-205847. [Epub ahead of print]

The developments of certain malignancies associated with chronic inflammatory diseases such as RA is known to occur to a greater extent than that of the general population. It is also know that certain RA treatments can affect malignancy rates. As such, newer immunomodulatory agents, such as the JAK inhibitor tofacitinib, are closely monitored for safety events of special interest, including malignancies. This paper analyses pooled malignancy data from the tofacitinib RA clinical development...