Exploring Sex-related Mechanisms of Psoriatic Arthritis (PSA) response to advanced therapies (EXSEMP): Individual participant data (IPD) meta-analysis of randomized controlled trials of advanced therapies

Lead Investigator: Lihi Eder, Women’s College Hospital
Title of Proposal Research: Exploring Sex-related Mechanisms of Psoriatic Arthritis (PSA) response to advanced therapies (EXSEMP): Individual participant data (IPD) meta-analysis of randomized controlled trials of advanced therapies
Vivli Data Request: 10030
Funding Source: None
Potential Conflicts of Interest: Lihi Eder received unrestricted educational and research grants for projects that are not related to this study from: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Fresenius Kabi; Consultation and participation in advisory boards: Abbvie, Janssen, BMS, UCB, Pfizer, Eli Lilly, Novartis, Fresenius Kabi. The proposed study is funded by local funds available through the Psoriatic Arthritis Research program at Women’s College Hospital. None of the pharmaceutical companies listed above provided funding for this study or is involved in any way in the current proposal. These potential conflicts will be disclosed in all presentation related to this project and in the manuscript that summarizes the results.

Summary of the Proposed Research:

Background: Psoriatic arthritis (PsA), a chronic inflammatory arthritis that affects 1 in 1000 adults, presents differently in males and females. Biologic treatment is a type of medical treatment that uses substances from living organisms to treat disease. Biologic treatments are effective yet costly medications for arthritis. However, female patients living with PsA are less likely to achieve remission with biologic treatments and are more likely to develop side effects. There is limited understanding of the reasons for these differences in response to treatment between males and females.

Objective: The objective of our study is to investigate whether certain types of biologic treatments are more effective and safer in females living with PsA. Additionally, we aim to study whether selected patient characteristics typically found in females, such as obesity, may explain the lower response to treatment in female patients.

Research Plan: We plan to perform a meta-analysis of data from randomized controlled clinical trials (RCTs) that evaluated biologic therapies in PsA. A meta-analysis combines the results of many studies on the same topic to see the overall picture. We have identified 40 trials that evaluated biologic therapies in PsA that we hope to include in our analysis. We will compare the effect of each biologic medication in male and female patients in each trial and then analyze these effects together in a meta-analysis to estimate the overall degree of sex difference in response to treatment. In addition, using statistical models across the different trials, we will evaluate how much of the response to treatment is influenced by factors associated with the sex of the patient, like body weight, level of inflammation, drug dose, and more. With this analysis, we hope to gain an understanding of the mechanisms explaining the expected poorer response in female patients.

Outcome: The results of our study could contribute to the development of sex-specific recommendations for prescribing biologic treatment in PsA, ultimately resulting in better patient care.

Requested Studies:

A Phase 4 Open-label Randomized Controlled Study COmparing the Effectiveness of Adalimumab iNTROduction and Methotrexate Dose escaLation in Subjects With Psoriatic Arthritis (CONTROL)
Data Contributor: AbbVie
Study ID: NCT02814175
Sponsor ID: M14-496

A Multi-Center Continuation Trial for Patients Completing Study M02-518 and M02-570 of the Human Anti-TNF Monoclonal Antibody Adalimumab (D2E7) in Patients With Moderate to Severely Active Psoriatic Arthritis
Data Contributor: AbbVie
Study ID: NCT00195689
Sponsor ID: M02-537

Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Moderate to Severely Active Psoriatic Arthritis Subjects With Inadequate Response to Disease Modifying Anti-Rheumatic Drug Therapy
Data Contributor: AbbVie
Study ID: NCT00646178
Sponsor ID: M02-570

Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Moderately to Severely Active Psoriatic Arthritis
Data Contributor: AbbVie
Study ID: NCT00646386
Sponsor ID: M02-518

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously in Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT00265096
Sponsor ID: CR006340

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFα Monoclonal Antibody, Administered Intravenously, in Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT02181673
Sponsor ID: CR103796

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Aanti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT01009086
Sponsor ID: CR016315

A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Ustekinumab, a Fully Human Anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-TNFalpha Agent(s)
Data Contributor: Johnson & Johnson
Study ID: NCT01077362
Sponsor ID: CR016483

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of CNTO 1275, a Fully Human Anti-IL-12 Monoclonal Antibody, Administered Subcutaneously, in Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT00267956
Sponsor ID: CR006322

A Multicenter, Randomized, Double-blind Trial of Anti-TNFa Chimeric Monoclonal Antibody (Infliximab) for the Treatment of Patients With Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT00051623
Sponsor ID: CR004789

A Randomized, Multicenter, International, Open-label Study of Infliximab Plus Methotrexate Versus Methotrexate (MTX) Alone for the Treatment of MTX naïve Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT00367237
Sponsor ID: P04422

Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNFα) Therapy
Data Contributor: Johnson & Johnson
Study ID: NCT03796858
Sponsor ID: CR108573

A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab in the Treatment of Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT02319759
Sponsor ID: CR105964

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects With Active Psoriatic Arthritis
Data Contributor: Johnson & Johnson
Study ID: NCT03158285
Sponsor ID: CR108219

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-TNF Alpha Agents
Data Contributor: Johnson & Johnson
Study ID: NCT03162796
Sponsor ID: CR108218

A 52-Week Multicenter, Randomized, Open-Label, Parallel- Group Study Evaluating the Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients With Psoriatic Arthritis Who Are Biologic Disease-Modifying Anti-Rheumatic Drug Naive
Data Contributor: Lilly
Study ID: NCT03151551
Sponsor ID: 16687

A Multicenter, Randomized, Double-Blind, Active and Placebo-Controlled 24-Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in Biologic Disease-Modifying Antirheumatic Drug-Naive Patients With Active Psoriatic Arthritis
Data Contributor: Lilly
Study ID: NCT01695239
Sponsor ID: 13731

A Multicenter, Randomized, Double-Blind, Placebo Controlled 24-Week Study Followed by Long Term Evaluation of Efficacy and Safety of Ixekizumab (LY2439821) in Biologic Disease-Modifying Antirheumatic Drug-Experienced Patients With Active Psoriatic Arthritis
Data Contributor: Lilly
Study ID: NCT02349295
Sponsor ID: 14310

A RANDOMIZED, OPEN-LABEL, TWO-PERIOD STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ETANERCEPT ON SKIN AND JOINT DISEASE IN PSORIASIS SUBJECTS WITH PSORIATIC ARTHRITIS
Data Contributor: Pfizer Inc.
Study ID: NCT00245960
Sponsor ID: 0881A5-401

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF TOFACITINIB (CP-690,550) OR ADALIMUMAB IN SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS Enquiry #119068 – data are available and can be requested – asked to submit study proposal
Data Contributor: Pfizer Inc.
Study ID: NCT01877668
Sponsor ID: NCT01877668

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE EFFICACY AND SAFETY OF 2 DOSES OF TOFACITINIB (CP-690,550) IN SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS AND AN INADEQUATE RESPONSE TO AT LEAST ONE TNF INHIBITOR Enquiry #119068 – Data is available and within the scope and can be requested
Data Contributor: Pfizer Inc.
Study ID: NCT01882439
Sponsor ID: NCT01882439