Publications

Filgotinib Versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and Inadequate Response to Methotrexate: A Phase III Randomised Clinical Trial

Ann Rheum Dis. 2021 Jan 27:annrheumdis-2020-219214

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

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 M...

Keywords:

• JAK,
• Fenebrutinib,
• Phase 3

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

Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510

Cohen SB,

van Vollenhoven RF,

Winthrop KL,

Zerbini CAF,

Tanaka Y,

Bessette L,

Zhang Y,

Khan N,

Hendrickson B,

Enejosa JV,

Burmester GR.

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 studie...

Keywords:

• JAK,
• Updacitinib,
• Safety,
• Phase 3

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

Drug Saf. 2020;43:379-392

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

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 stu...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• Real-World

Highlights of 2019

Please click the links below to go to the CSF review of each paper

McInnes. I

2019 was another remarkable year in cytokine signalling. We can be optimistic that clinical practice for inflammatory arthritis will continue to improve, with promising long-term safety data supporting the use of established JAK inhibitors; tofacitinib and baricitinib, in addition to exciting phase III clinical data for filgotinib and newly approved upadacitinib. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respecti...

Keywords:

• Review

Risk Factors for Major Adverse Cardiovascular Events in Phase III and Long-Term Extension Studies of Tofacitinib in Patients with Rheumatoid Arthritis

Arthritis Rheumatol .2019 Sep;71(9):1450-1459. doi: 10.1002/art.40911. Epub 2019 Aug 6.

Christina Charles-Schoeman,

Ryan DeMasi,

Hernan Valdez,

Koshika Soma,

Lie-Ju Hwang,

Mary G. Boy,

Pinaki Biswas,

Iain B. McInnes

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 after 24 weeks...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3,
• LTE,
• Cardiovascular

Efficacy and Safety of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III Randomised, Double-Blind, Placebo-Controlled Trial (RAJ4) in Japan

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

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

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 M...

Keywords:

• JAK,
• Peficitinib,
• Phase 3

Clinical Outcomes in Patients Switched from Adalimumab to Baricitinib Due to Non-Response and/or Study Design: Phase III Data in Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2019 Jul;78(7):890-898.

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

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 from ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3

A Systematic Review and Meta-Analysis of Infection Risk with Small Molecule JAK Inhibitors in Rheumatoid Arthritis

Rheumatology (Oxford). DOI: 10.1093/rheumatology/kez087

Bechman K,

Subesinghe S,

Norton S,

Atzeni F,

Galli M,

Cope AP,

Winthrop KL,

Galloway JB

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 p...

Keywords:

• JAK,
• Safety,
• Meta analysis,
• Infections

Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis.

Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

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

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 sub...

Keywords:

• JAK,
• Baricitinib,
• Basic Science,
• MOA

Lipid Profile and Effect of Statin Treatment in Pooled Phase II and Phase III Baricitinib Studies

Ann Rheum Dis. 2018 Jul;77(7):988-995. DOI 10.1136/annrheumdis-2017-212461

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

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 of ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Safety,
• Cardiovascular