Clinical and molecular data to predict flares in DMARD optimization in rheumatoid arthritis: a randomized, controlled, open-label, non-inferiority trial

OBJECTIVES: The aim of this study was to identify robust predictive markers which may help personalize tapering protocols, minimizing flare risk while optimizing long-term disease management in RA patients. METHODS: The OPTIBIO trial (EudraCT 2012-004482-40) was a phase IV, randomized, open-label, non-inferiority study conducted in five hospitals in Spain. RA patients in sustained remission on stable bDMARD therapy were randomized 1:1 to standard care or dose reduction. The primary outcome was to compare the proportion of joint flare between baseline and 12 months by a non-inferiority analysis analysed by the intention-to-treat principle and to identify predictors for flare and sustained remission. RESULTS: A total of 195 patients were randomized: 99 to the control group and 96 to the optimization group. Thirty-nine flares occurred (optimization: 22.7%, control: 17.2%), with a risk difference of -5.5% (95% CI: -16.8% to 5.7%; P = 0.33). Two predictive models were developed: one for flares (AUC: 0.84) including 3v-DAS28-CRP, VAS pain, erosions, systolic blood pressure and haemoglobin, and another for sustained remission (AUC: 0.77) including 3v-DAS28-CRP, age and rheumatoid factor. Adding molecular biomarkers improved AUCs to 0.91 and 0.88, respectively. No significant differences in adverse events were observed. CONCLUSION: bDMARD dose optimization was not non-inferior to standard therapy on the flare rate but demonstrated similar safety. Predictive models for remission and flares were developed, which may help select patients to ensure safe implementation of this strategy, highlighting the need for personalized treatment. TRIAL REGISTRATION: www.clinicaltrialsregister.eu; EudraCT 2012-004482-40.