Objective: For DMARD-naïve, early rheumatoid arthritis patients who achieved sustained low disease activity (sLDA; DAS28[ESR]≤3.2 at both Weeks 40 and 52) after 1 year of treatment with certolizumab pegol (CZP 200mg Q2W+optimized MTX), we evaluated whether continuation of CZP as a standard (200mg Q2W+MTX) or reduced-frequency (200mg Q4W+MTX) dose was superior to stopping CZP (placebo+MTX) in maintaining LDA for 1 additional year. Methods: 293 patients from C-EARLY Period 1 were re-randomized 2:3:2 in Period 2 to CZP standard (n=84), reduced-frequency (n=127), CZP stopped (n=82). The primary endpoint was the percentage of patients who maintained LDA throughout Weeks 52-104 without flares. Hierarchical testing scheme: CZP standard versus CZP stopped, if p<0.05 achieved, then CZP reduced-frequency versus CZP stopped (non-responder imputation). Results: 36% fewer patients than projected achieved sLDA in Period 1 and were eligible for enrollment in Period 2. A higher proportion of CZP standard and reduced-frequency patients maintained LDA versus CZP stopped (48.8% [p=0.112], 53.2% [p=0.041; nominal p value, first hierarchical test not significant] versus 39.2%). Similar trends were observed for radiographic non-progression (change from baseline mTSS≤0.5; 79.2%, 77.9% versus 70.3%) and normative physical function (HAQ-DI≤0.5; 71.4%, 70.6% versus 57.0%). Safety profiles were similar between all groups, with no new safety signals identified for continuing CZP to Week 104. No deaths were reported. Conclusion: The study failed to meet its primary endpoint. However, there were no clinically meaningful differences between the standard or reduced-frequency doses of CZP+MTX; both more effectively controlled rheumatoid arthritis in comparison to CZP withdrawal.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)