97. Final 5-Year Safety and Efficacy Results of a Phase 3, Randomized, Placebo-Controlled Trial of Golimumab in Methotrexate-NaïVe Patients with Rheumatoid Arthritis

Abstract

randomized controlled trial (RCT)—the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial—to examine whether responses to intensive combination treatments in early RA differ by ACPA status. Methods: The CARDERA trial randomized 467 patients with early active RA to receive: (i) MTX (ii) MTX/ciclosporin (iii) MTX/prednisolone or (4) MTX/ciclosporin/prednisolone in a factorial-design. Patients were assessed 6 monthly for 2 years. In this analysis we evaluated 431 patients with archived serum available for ACPA status determination (using the anti-CCP2 ELISA assay). To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, DAS28, HAQ, EuroQol, PCS and MCS scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point stratified by ACPA status using t-tests. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. Results: Of the 431 RA cases, 310 (72%) were ACPA-positive; 121 (28%) were ACPA-negative. ACPA status influenced the effect of treatment on radiological progression, with a significant ACPA*treatment interactive effect on Larsen score changes seen in the ANOVA model (P< 0.001). ACPA-positive patients had significant reductions in Larsen score progression with all treatments; no effect was seen in ACPAnegative RA. ACPA-positive patients receiving triple therapy had the greatest benefits: mean Larsen score increases over 2 years were 3.66 (95% CI 2.27, 5.05) with triple therapy and 9.58 (95% CI 6.76, 12.39) with monotherapy; OR for new erosions with triple therapy vs monotherapy was 0.32 (95% CI 0.14, 0.72; P1⁄40.003). ACPA-negative patients had minimal radiological progression irrespective of treatment strategy: mean Larsen score increases over 2 years comprised 1.70 (95% CI 0.29, 3.10) with triple therapy and 2.72 (95% CI 1.15, 4.29) with monotherapy; only 7% developed new erosions. The beneficial effects of high-dose corticosteroids on reducing disease activity and improving physical health were confined to ACPA-positive RA. Conclusion: ACPA status influences the need for, and response to, combination DMARDs and high-dose tapering corticosteroids in early RA. Combination DMARDs and corticosteroids only provided radiological, disease activity and physical health benefits in ACPA-positive patients. This suggests that current UK guidelines advocating combination DMARDs and corticosteroids in all early active RA patients require reconsideration. Funding: This research was supported Arthritis Research UK [Grant Number 19739 to ICS], the National Institute for Health Research (NIHR) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. Disclosure statement: The authors have declared no conflicts of interest.