Phase 2 trial finds hydroxychloroquine does not prevent rheumatoid arthritis in at-risk individuals

OBJECTIVE: Individuals with serum elevations of anti-cyclic citrullinated peptide (anti-CCP) antibodies are at increased risk for future rheumatoid arthritis (RA). No pharmacologic interventions have been approved for the prevention of RA in such at-risk individuals. However, hydroxychloroquine (HCQ) is used without supporting clinical trial evidence. METHODS: In this phase 2 randomized trial, individuals at risk for RA with anti-CCP3 ≥2 times the upper limit of normal (ULN) were assigned to receive HCQ or placebo for 12 months, with up to 24 months of postdrug follow-up. The primary outcome was the development of clinical RA, as defined in the protocol, at 36 months. Secondary outcomes included safety, development of inflammatory arthritis (IA), and participant-reported joint symptoms. RESULTS: Of 144 randomized participants, 71 were assigned to HCQ and 73 to placebo. In the modified intent-to-treat population, clinical RA occurred in 21 of 69 (30.4%) participants in the HCQ group and 24 of 73 (32.9%) in the placebo group. The risk of clinical RA at 36 months was 0.336 with HCQ and 0.394 with placebo (difference -0.058; 95% confidence interval -0.336 to 0.220; P = 0.52). Results for IA were similar. The occurrence and severity of joint symptoms were not observed to differ between groups. Adverse event incidence was similar between groups. CONCLUSION: In this trial involving individuals with anti-CCP3 levels ≥2 times the ULN, 12 months of HCQ did not prevent the development of clinical RA at 36 months.