Lead Investigator: Katie Bechman, King’s College London
Title of Proposal Research: Effects of obesity on treatment response to Janus kinase inhibitors (JAKi) in rheumatoid arthritis
Vivli Data Request: 10560
Funding Source: KB is funded on a National Institute for Health and Care Research (NIHR) Clinical Lectureships.
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Project Overview
This study aims to investigate how obesity influences the effectiveness of Janus kinase inhibitors (JAKi), a class of immunotherapies used to treat rheumatoid arthritis (RA). By combining data from multiple studies, the research seeks to provide a deeper understanding of how body weight impacts treatment outcomes for these drugs.
Context and background of the study topic
Obesity is a significant and growing global health issue, with rising prevalence and widespread negative effects on health that go beyond metabolic and cardiovascular complications. Among individuals with RA, obesity is even more common, affecting approximately 1 in 4 patients. Rheumatoid arthritis is an autoimmune disease, which means that the immune system (which usually fights infection) attacks the cells that line the joints by making them swollen, stiff and painful. Adipose tissue (body fat) in obese individuals contains elevated levels of pro-inflammatory immune cells, which contribute to the chronic inflammation underlying RA disease activity.
Summary of Existing Research
Emerging evidence indicates that obesity can make it more challenging for patients with RA to reduce inflammation and achieve effective disease control with immunotherapies. However, there is limited research on how obesity specifically impacts the response to Janus kinase inhibitors (JAKi) These immunotherapies target Janus kinase enzymes, which play a central role in the inflammatory pathways driving RA, thereby helping to reduce joint swelling, pain, and tissue damage. JAK inhibitors are being used increasingly in RA treatment, supported by robust evidence of their effectiveness.
Rationale for the Study
Analysing data from all JAKi clinical trials offers a unique opportunity to study a larger and more diverse patient population, including those in severely obese categories. This approach also enables direct comparison with other immunotherapies. Using individual participant data has several benefits over aggregate data, permitting the analysis all important outcomes and using a consistent unit and method of analysis. It is vital for us to understand how obesity interacts with JAKi. Not only will this inform therapeutic decisions in clinical practice, but it may also support the proactive utilisation of novel weight-loss strategies alongside immunotherapy in the ultimate goal of improving outcomes for individuals with RA.
Requested Studies:
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo on Stable Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs)
Data Contributor: AbbVie
Study ID: NCT02706847
Sponsor ID: M13-542
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to MTX
Data Contributor: AbbVie
Study ID: NCT02706951
Sponsor ID: M15-555
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Once Daily Monotherapy to Methotrexate (MTX) Monotherapy in MTX-Naïve Subjects With Moderately to Severely Active Rheumatoid Arthritis
Data Contributor: AbbVie
Study ID: NCT02706873
Sponsor ID: M13-545
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs
Data Contributor: AbbVie
Study ID: NCT02675426
Sponsor ID: M13-549
A Phase 3, Randomized, Active-Controlled, Double-Blind Study Comparing Upadacitinib (ABT-494) to Abatacept in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs) on Stable Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs)
Data Contributor: AbbVie
Study ID: NCT03086343
Sponsor ID: M15-925
Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. FINCH 1 comparing filogotinib to placebo or adalimumab in MTX-inadequate responder. We are aiming to obtain data for the Filgotinib studies (NCT02889796, NCT02873936, NCT02886728) and to bring it into the Vivli research environment when possible.
Data Contributor: I WILL BRING MY OWN
Study ID: NCT02889796
Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial FINCH 2 comparing filogotinib to placebo in csDMARDs-inadequate responder. We are aiming to obtain data for the Filgotinib studies (NCT02889796, NCT02873936, NCT02886728) and to bring it into the Vivli research environment when possible.Lay summary
Data Contributor: I WILL BRING MY OWN
Study ID: NCT02873936
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 FINCH 3 comparing filogotinib to methotrexate in MTX-naive patients We are aiming to obtain data for the Filgotinib studies (NCT02889796, NCT02873936, NCT02886728) and to bring it into the Vivli research environment when possible.Lay summary
Data Contributor: I WILL BRING MY OWN
Study ID: NCT02886728
A Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
Data Contributor: Lilly
Study ID: NCT01710358
Sponsor ID: 13978
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors
Data Contributor: Lilly
Study ID: NCT01721044
Sponsor ID: 14058
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs With Moderately to Severely Active Rheumatoid Arthritis
Data Contributor: Lilly
Study ID: NCT01721057
Sponsor ID: 14059
A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment With Disease-Modifying Antirheumatic Drugs
Data Contributor: Lilly
Study ID: NCT01711359
Sponsor ID: 14062
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
Data Contributor: Lilly
Study ID: NCT02265705
Sponsor ID: 14875
Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate With Inadequate Response To TNF Inhibitors
Data Contributor: Pfizer Inc.
Study ID: NCT00960440
Sponsor ID: A3921032
Phase 3 Randomized, Double Blind, Placebo Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
Data Contributor: Pfizer Inc.
Study ID: NCT00847613
Sponsor ID: A3921044
Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP-690,550 Monotherapy In Patients With Active Rheumatoid Arthritis
Data Contributor: Pfizer Inc.
Study ID: NCT00814307
Sponsor ID: A3921045
Phase 3, Randomized, Double Blind, Placebo Controlled Study Of The Safety And Efficacy Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background DMARDS
Data Contributor: Pfizer Inc.
Study ID: NCT00856544
Sponsor ID: A3921046
Phase 3 Randomized, Double-Blind, Active Comparator, Placebo-Controlled Study Of The Efficacy And Safety Of 2 Doses Of CP 690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate
Data Contributor: Pfizer Inc.
Study ID: NCT00853385
Sponsor ID: A3921064
Phase 3 Randomized, Double-blind Study Of The Efficacy And Safety Of 2 Doses Of Cp-690,550 Compared To Methotrexate In Methotrexate Navie Patients With Rheumatoid Arthritis
Data Contributor: Pfizer Inc.
Study ID: NCT01039688
Sponsor ID: A3921069
A Phase 3b/4 Randomized Double Blind Study Of 5 Mg Of Tofacitinib With And Without Methotrexate In Comparison To Adalimumab With Methotrexate In Subjects With Moderately To Severely Active Rheumatoid Arthritis
Data Contributor: Pfizer Inc.
Study ID: NCT02187055
Sponsor ID: A3921187