Cytokine Signalling Forum

Publications





February 21

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial

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...

November 20

Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase III Clinical Programme

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...

July 20

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

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...

May 20

An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis Across Phase III and Long Term Extension Studies with Comparison to Real World Observational Data

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...

February 20

EULAR Recommendations for the Management of Rheumatoid Arthritis – 2019 Update and Consensus Statement on JAKinibs

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...

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.

February 19

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...

September 18

Subkutan Tocilizumab ile Tedavi Edilen Romatoid Artrit Hastalarında Metotreksat Tedavisinin Kesilmesi Sonrası Devam Eden Yanıt

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: Toz

July 18

Hastalığı Modifiye Edici Konvansiyonel Sentetik Anti-Romatizmal İlaçlara Yetersiz Yanıtlı Romatoid Artritli Hastalarında Upadacitinib Etkinliği ve Güvenliği (SELECT-NEXT): Randomize, Çift Kör, Plasebo Kontrollü Faz 3 Çalışma

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: Toz

May 17

Metotreksat-Naif Erken Romatoid Artritli Hastalarda Metotreksat Monoterapisi veya Tocilizumab Kombinasyonu veya Monoterapisi: Randomize, Plasebo Kontrollü FUNCTION Çalışmasından 2 Yıllık Klinik ve Radyografik Sonuçlar

Burmester GR, Rigby WF, van Vollenhoven RF, Kay J, Rubbert-Roth A, Blanco R, Kadva A and Dimonaco S.
Ann Rheum Dis Published Online First: 7 April 2017. Doi 10.1136/annrheumdis-20160210561

Burmester et al. present data showing that 52-week efficacy and safety of intravenous tocilizumab plus methotrexate, or tocilizumab monotherapy are maintained through to Week 104 in patients with early rheumatoid arthritis. Patients were assigned to four treatment groups: 4 mg/kg TCZ + MTX, 8 mg/kg TCZ + MTX, 8 mg/kg TCZ + placebo or placebo + MTX. Patients not achieving DAS28 ≤3.2 at Week 52 and who were not receiving 8 mg/kg TCZ were rescued to 8 mg/kg TCZ + MTX. Of the 1162 randomly assi...

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

Translated by: Bahtiyar Toz

March 17

Romatoid Artrit Hastalarında Selektif JAK-1 inhibitörü olan ABT-494 Faz 2b Çalışması

Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL and Jungerwirth S.
Arthritis Rheumatol 2016;68:2857–66

The summary and accompanying slide deck have been developed in conjunction with the Kremer et al. study (Study 2) which examined ABT-494 in TNF-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor. Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant ...

Keywords: JAK, Upadacitinib, Clinical, Phase 2

Translated by: Bahtiyar Toz

December 16

TNF İnhibitörlerine Yetersiz Yanıtlı veya İntolerans olan Aktif RA Hastalarında Sarilumab ve Biyolojik Olmayan Hastalık Modifıye Edici Antiromatizmal İlaçlar

Fleischmann R, van Adelsberg J, Lin Y, da Rocha, Castelar-Pinheiro G, Brzezicki J, Hrycaj P, Graham NMH, van Hoogstraten H, Bauer D, Burmester GR.
Arthritis Rheumatol 2016. DOI:10.1002/art.39944.

In this Phase 3 study (TARGET) of TNF-IR patients, sarilumab plus csDMARD(s) demonstrated clinical efficacy and improvements in physical function versus placebo plus csDMARD(s). Patients (N=546) were randomised 1:1:1 to sarilumab 150 mg, 200 mg Q2W or placebo (all plus csDMARD[s]). Two co-primary endpoints versus placebo were investigated: ACR20 response rate at Week 24, and HAQ-DI change from baseline at Week 12. As well as improvements in ACR20 responses (33.7% vs 55.8 and 60.9%, for placebo...

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

Translated by: Bahtiyar Toz

Aktif Romatoid Artrit Hastalarında Sarilumab Monoterapisinin Adalimumab Monoterapisine Göre Etkinlik ve Güvenliğinin Değerlendirilmesi (MONARCH): Randomize, Çift-Kör, Paralel-Grup Faz III Çalışma

Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NMH, van Hoogstraten H, Bauer D, Vargas JI, Lee E-B.
Ann Rheum Dis 2016. DOI 10.1136/annrheumdis-2016-210310

In this Phase 3 superiority study (MONARCH) of patients with active RA who should not continue treatment with MTX because of intolerance or inadequate response, sarilumab monotherapy demonstrated superior efficacy to adalimumab (ADA) monotherapy. Patients receiving sarilumab versus ADA also reported greater improvement in health status, including a trend towards greater improvement in fatigue. In this randomised, multicentre study, patients received sarilumab 200 mg Q2W plus placebo (n=184) or ...

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

Translated by: Bahtiyar Toz

October 14

Aktif romatoid artritli hastaların üçüncü-sıra tedavisinde metotreksat ile birlikte tofacitinib: Bir Faz 3 çalışmadan hastaların-bildirdiği sonuçlar

Strand V, Burmester GR, Zerbini CA, Mebus CA, Zwillich SH, Gruben D, Wallenstein GV.
Arthritis Care Res (Hoboken). 2014 Sep 3. doi: 10.1002/acr.22453. [Epub ahead of print]

For many patients with rheumatoid arthritis, improvements in pain, physical function, fatigue, and health-related quality of life (HRQoL) are more important and meaningful than improvements in joint swelling, tenderness, or inhibition of structural damage. These patient-perceived benefits of RA therapy contribute importantly to overall clinical efficacy. This paper presents patient-reported outcomes (PROs) form the ORAL Step trail, which assessed tofacitinib 5 mg or 10 mg twice daily, or pla...

Keywords: JAK, Tofacitinib, Clinical, PRO

Translated by: Ege Sinan TORUN

June 13

Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial

Burmester GR, Blanco R, Charles-Schoeman C, et al.
The Lancet 2013; 381(9865):451-60

The ORAL Step trial is one of six studies conducted as part of the phase 3 research programme for the oral Janus kinase (JAK) inhibitor tofacitinib. This 6-month, double-blind, parallel-group phase 3 study investigated the efficacy and safety of tofacitinib in adults with moderate to severe rheumatoid arthritis (RA) with an inadequate response to tumour necrosis factor (TNF) inhibitors. Patients were randomised to 5 or 10 mg tofacitinib twice daily or placebo, which was switched to tofaciti...