Patient-Reported Outcomes Following Discontinuation Of Tumor Necrosis Factor Inhibitors In Rheumatoid Arthritis Remission/Low Disease Activity: A Randomized Placebo-Controlled Trial

OBJECTIVE: To compare changes in patient-reported outcomes (PROs) over 48 weeks between patients with rheumatoid arthritis (RA) in remission/low disease activity who discontinued treatment with tumor necrosis factor inhibitors (TNFi) and those who continued TNFi treatment. METHODS: In this double-blind placebo-controlled randomized trial, patients with RA in sustained remission/low disease activity treated with TNFi were randomly assigned to placebo (i.e discontinuation of TNFi) or continuation of TNFi. Patients completed PROs, including the patient global assessment (PGA), pain scale, Health Assessment Questionnaire (HAQ), Fatigue Severity Scale, and Short Form-36 (SF36), at randomization and every 12 weeks for 48 weeks. We compared PROs over time between treatment groups using generalized estimating equations. We also compared mean changes from baseline at each time point, and separately among patients who relapsed. RESULTS: Sixty-nine patients were randomized to placebo and 33 patients were randomized to the TNFi group. Over the trial, group mean scores on the PGA, pain score, and HAQ were significantly higher in the placebo group than in the TNFi group. Effect sizes were small or moderate for all PROs. Compared to Week 0, all measures were significantly higher in the placebo group at Week 12, but not at later times, in paired analyses, corresponding to the timing of most relapses. Pain and social function were the domains most affected. PROs returned to baseline values by trial end, after resumption of TNFi treatment. CONCLUSION: PROs generally worsened shortly after TNFi discontinuation in patients with RA, but recovered promptly when reinstituted. Trial registration NCT01793519.