Evaluation of Response Criteria in Rheumatoid Arthritis Treated With Biologic Disease-Modifying Antirheumatic Drugs

Objective Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity. We undertook this study to examine the agreement between the European League Against Rheumatism (EULAR) response based on the erythrocyte sedimentation rate (ESR) or C-reactive protein level, the Simplified Disease Activity Index 50% response measure (SDAI50), and the Clinical Disease Activity Index 50% response measure (CDAI50) in patients treated withIL-6i and otherbDMARDs. Methods We enrolled 306 patients withRAwho started or switchedbDMARDs. Treatment response at 6 months was analyzed. Kappa statistics were used to evaluate the agreement between different response measures. The contribution ofAPRs to improvement in disease activity scores was examined. The change of Health Assessment Questionnaire (HAQ) score was analyzed inIL-6i-treated patients. Results Good agreement was achieved between response measures, with kappa >0.6 in patients treated with tumor necrosis factor inhibitors or cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein. InIL-6i-treated patients, the agreement was low between theEULARresponse (ESR) and theSDAI50 or theCDAI50 (kappa = 0.43 and 0.37, respectively). UnderIL-6i treatment,APRimprovement accounted for 56.0% of total improvement of the Disease Activity Score in 28 joints (DAS28) using the ESR. When discordance was found between theCDAI50 andEULARresponse inIL-6i-treated patients, all patients were classified asEULAR-only responders; there was noHAQimprovement inEULAR-only responders. Conclusion EULARresponse criteria overestimate the response underIL-6i treatment because theAPRimprovement largely contributes to theDAS28 improvement.