Defining the Optimal Strategies for Achieving Drug-Free Remission in Rheumatoid Arthritis: A Narrative Review

Abstract

Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; however, it is recommended that patients can taper therapy, with a view to discontinuing and achieving drug-free remission if treatment goals are maintained. This narrative review aims to present the current literature on drug-free remission in rheumatoid arthritis, with a view to identifying which strategies are best for disease-modifying anti-rheumatic drug (DMARD) tapering and to highlight areas of unmet clinical need. Methods: We performed a narrative review of the literature, which included research articles, meta-analyses and review papers. The key search terms included were rheumatoid arthritis, remission, drug-free remission, b-DMARDS/biologics, cs-DMARDS and tapering. The databases that were searched included PubMed and Google Scholar. For each article, the reference section of the paper was reviewed to find additional relevant articles. Results: It has been demonstrated that DFR is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. Conclusions: DFR in RA may be an achievable goal in certain patients. This carries importance in reducing medication-induced side-effects and potential toxicity, the burden of taking treatment if not required and cost effectiveness, specifically for biologic therapy. Prospective studies of objective biomarkers will help facilitate the prediction of successful treatment discontinuation.

Early persistence on therapy impacts drug-free remission: a case-control study in a cohort of Hispanic patients with recent-onset rheumatoid arthritis

“…The absence of disease-specific autoantibodies is the most consistent and best predictor [2,3,6]. Meanwhile, symptom duration has arisen conflicting results, which might be explained by a non-linear association with DFR but refined to a short period, the window of opportunity [2,3,7]. Additional factors identified are a longer duration of SR before the drug withdrawal [8], lower disease activity at the time of treatment cessation [9][10][11][12], using methotrexate as the last DMARD before withdrawal [9], circulating inflammatory biomarkers and peripheral CD4+ T-cell gene expression [11], and a model that combined RA quality of life (QoL) score, musculoskeletal ultrasound-derived information, and the percentage of inflammation-related T-cell [13].…”

“…DFR status was defined when patients achieved SR (at least 1 year of continuous follow-up clinical assessments with DAS28 ≤ 2.6) without concomitant DMARDs and corticosteroids (any route). The definition combined characteristics from previously published definitions [2,3].…”

“…Also, the 21-month cutoff highlights that patients need to adhere (closely and) early on during their follow-up to treatment recommendations if significant outcomes are desired. In regard to the predictors of DFR, different factors have been described, although PT has never been examined [2,3,6,12,45,46]. Genetical [2], immunological [2,3], imaging [3], and clinical associations [3] with predictors of DFR have been consistently identified, including the presence of autoantibodies, absence of power Doppler signal on musculoskeletal ultrasound, lower disease activity, and PROs at treatment cessation.…”

“…Current treatment guidelines for rheumatoid arthritis (RA) suggest tapering disease-modifying anti-rheumatic drugs (DMARDs) when patients are in sustained remission (SR) [1]. Two recent systematic literature and narrative reviews inform that with a treat-to-target approach, an increasing number of patients might achieve and sustain DMARD-free remission (DFR), with frequencies ranging from 3.6 to 22% of the patients [2,3]. (Sustained) DFR has nowadays considered the closest state to RA cure [4] and, from the patient perspective, has been associated with the reversal of functional disability and the resolution of symptoms such as fatigue [5].…”

“…Several factors had been demonstrated to predict the successful maintenance of remission after classical DMARDs withdrawal. The absence of disease-specific autoantibodies is the most consistent and best predictor [2,3,6]. Meanwhile, symptom duration has arisen conflicting results, which might be explained by a non-linear association with DFR but refined to a short period, the window of opportunity [2,3,7].…”