Is it possible to withdraw biologics from therapy in rheumatoid arthritis?

Background: Biologic agents targeting tumor necrosis factor (TNF) have revolutionized the treatment of rheumatoid arthritis (RA). Clinical remission is perceived as a realistic primary goal, and its maintenance leads to structural and functional remission.

Objective: This study reviews whether discontinuation of biologic agents is possible after sustained remission and discusses its significance from the risk/benefit point of view (including safety and health economic considerations).

Methods: Using a strategic PubMed search, 45 original research articles regarding discontinuation of biologic agents were identified; 7 were selected that had an obvious focus on discontinuation of biologic agents. These articles included the TNF20, BeSt (Behandel Strategieen), and RRR (Remission Induction by Remicade in RA) studies. However, because of the limitations of the original search, we also review here some articles that did not focus mainly on discontinuation of biologic agents but that presented data regarding biologic-free control. These studies included OPTIMA (Optimal Protocol for Treatment Initiation With MTX and Adalimumab), PRESERVE, and CERTAIN, as well as some recent findings in the HONOR (Humira Discontinuation Without Functional and Radiographic Damage Progression Following Sustained Remission) study from our department.

Results: In BeSt and OPTIMA, clinical remission was sustained without functional progression by discontinuing TNF inhibitors, after reducing disease activity by using TNF inhibitors and methotrexate (MTX), in patients with early RA and who were MTX naive. In some studies (including RRR and HONOR), the discontinuation of TNF inhibitors after sustained remission was possible in some patients with long-standing RA who had an inadequate response to MTX. When disease activity flared up after treatment discontinuation, re-treatment with infliximab or adalimumab was highly effective and safe in the majority of patients. It is also clear that tight control with TNF inhibitors and MTX seems to be a prerequisite for having a better chance of biologic-free remission.

Conclusions: Intensive treatment with TNF inhibitors may change the disease process of RA and potentially offers the possibility of a "treatment holiday" from biologic agents.