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Center for Global Research Data

Long-term predictive value of patient global assessment regarding radiographic damage and physical function in patients with Rheumatoid Arthritis: individual patient data meta-analysis

Lead Investigator: Jose Antonio Pereira da Silva, Universidade de Coimbra, Portugal
Title of Proposal Research: Long-term predictive value of patient global assessment regarding radiographic damage and physical function in patients with Rheumatoid Arthritis: individual patient data meta-analysis
Vivli Data Request: 5985, 5327
Funding Source: None
Potential Conflicts of Interest: JAPS reports a research grant from Pfizer and Abvvie, and speaker fees from Pfizer, AbbVie, Roche, Lilly, Novartis. These potential conflicts will be disclosed in all papers resulting from this project.

Summary of the Proposed Research:

The treatment of Rheumatoid Arthritis (RA) has improved remarkably over recent years, due to not only the development of new therapies but also novel treatment strategies. Among these, the Treat-to-Target (T2T) recommendation epitomizes the consensual concept that disease treatment should aim at achieving, as early and consistently as possible, a target of level of remission, or at least low disease activity. To assess if the target is achieved or not physicians use composite indices that include different variables. The most common variables used in these indices (or remission definitions) are: number of tender (TJC28) and swollen joint counts (SJC28), a inflammatory parameter (blood analysis) and a patient reported outcome (PRO) designed by “Patient Global Assessment” (PGA). In this PGA the patients is questioned “Considering all the ways your arthritis has affected you, how do you feel your arthritis is today?” and asked to rate it from 0 to 100.

This study is designed to clarify whether PGA should or not be used to guide immunosuppressive therapy and evaluate its results in RA.

To this purpose we will test the relationship between two different definitions of disease remission and long-term outcomes in terms of structural damage (X-Rays) and function. The states of remission will be categorized as follows:
-“4v-Remission”: the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean-based definition[5]: TJC28<=1, SJC28<=1, C-reactive protein (CRP) in mg/dl<=1, and PGA<=1/10.
-“3v-Remission”: as above, excluding PGA.

Analyses will also specifically address the outcomes of patients that achieve 3v but not 4v-Remission (i.e. distinguished by only PGA). To achieve this goal on the most robust way we are trying to pool together individual level patient data from as many randomized clinical trials (RCT) as possible, including studies from different pharmaceutical companies.

A number of secondary outcomes will also be addressed including whether the relationship between remission states (i.e. 3v and 4v-remission) and long-term outcome is influenced by treatment arm and other factors (e.g. age, gender, co-medication, disease duration, other), over time.

Expected result include the demonstration that the value and efficacy of available biologic therapies is actually higher than previously acknowledged and also that PGA should not be included in the definition of the target for immunosuppressive therapy. This does not mean that the patient perspective should be disregarded. By the contrary, we support that, once disease control is achieved, adjunctive therapy of a different nature (pharmacological and/or nonpharmacological) should be guided by patients’ perspective, but maybe using more informative tools than PGA.

Requested Studies:

A Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER).
Sponsor: AbbVie
Study ID: NCT00195663
Sponsor ID: DE013

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate
Sponsor: Abbvie
Study ID: NCT00195702
Sponsor ID: DE019

A Phase III Multi-center, Double-blind, Placebo-controlled, Parallel Group 24-Week Study to Assess the Efficacy and Safety of Two Dose Regimens of Liquid Certolizumab Pegol as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate.
Sponsor: UCB
Study ID: NCT00160602
Sponsor ID: C87050

A Phase III Multicentre, Double Blind, Placebo-controlled, Parallel Group 52-week Study to Assess the Efficacy and Safety of 2 Dose Regimens of Lyophilised CDP870 as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate
Sponsor: UCB
Study ID: NCT00152386
Sponsor ID: C87027

A Phase III Multi-centre, Open-label, follow-on Study to CDP870-027, to Assess the Efficacy and Safety of Lyophilized CDP870 an Engineered Human Anti-TNF PEG Conjugate, as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis
Sponsor: UCB
Study ID: NCT00175877
Sponsor ID: C87028

A Phase III Multi-center, Open-label, Follow-up Study, to Assess the Safety and Efficacy of Liquid Certolizumab Pegol as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and in the Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis Who Participated in Study CDP870-050
Sponsor: UCB
Study ID: NCT00160641
Sponsor ID: C87051

A Double-Blind Study Evaluating the Efficacy and Safety of the Combination of Etanercept and Methotrexate in Comparison to Etanercept Alone or Methotrexate Alone in Rheumatoid Arthritis Patients
Sponsor: Pfizer Inc.
Study ID: NCT00393471

A 24-Month,Randomized,Double-Blind,Two-Period Study to Evaluate the Efficacy and Safety of the Combination of Etanercept and Methotrexate and Methotrexate Alone in Subjects With Early Rheumatoid Arthritis
Sponsor: Pfizer Inc.
Study ID: NCT00195494

(Note: Additional studies added as part of Data Request 5985)

A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis
Sponsor: Roche
Study ID: NCT00106535
Sponsor ID: WA17823

A Randomized, Double-blind, Parallel Group Study of Safety and the Effect on Clinical Outcome of Tocilizumab Subcutaneous (sc) Versus Placebo sc in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs) in Patients With Moderate to Severe Active Rheumatoid Arthritis
Sponsor: Roche
Study ID: NCT01232569
Sponsor ID: NA25220

A Multi-center, Randomized, Double-blind, Parallel Group Study of the Safety, Disease Remission and Prevention of Structural Joint Damage During Treatment With Tocilizumab (TCZ), as a Monotherapy and in Combination With Methotrexate (MTX), Versus Methotrexate in Patients With Early, Moderate to Severe Rheumatoid Arthritis
Sponsor: Roche
Study ID: NCT01007435
Sponsor ID: WA19926

A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Alpha Therapies
Sponsor: Roche
Study ID: NCT00468546
Sponsor ID: WA17042

An Open Label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera/Rituxan) in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNFa Therapies
Sponsor: Roche
Study ID: NCT02097745
Sponsor ID: WA17531

A Randomized, Phase 3, Controlled, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate (MTX) Compared to MTX Alone, in Methotrexate-Naive Patients With Active Rheumatoid Arthritis
Sponsor: Roche
Study ID: NCT00299104
Sponsor ID: U3373g