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

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 [1]. Among these, the Treat-to-Target (T2T) recommendation [2,3] 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 [3,4]. 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?"[5] 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.