Spacing of a TNF inhibitor or dose reduction of methotrexate vs continued treatment in patients with rheumatoid arthritis in remission or low disease activity: a randomised, controlled trial (SORAIRO trial)

OBJECTIVES: This study aimed to assess the noninferiority of spacing a tumour necrosis factor (TNF) inhibitor or reducing the methotrexate dose with continued treatment in patients with rheumatoid arthritis. METHODS: The SORAIRO trial was a multicentre, open-label, randomised, noninferiority study. Patients who had been in remission or low disease activity based on the Clinical Disease Activity Index (CDAI) in the preceding phase III trial of ozoralizumab, a next-generation TNF inhibitor, were enrolled. The precalculated sample size was 141. Patients were randomised into continued treatment, ozoralizumab spacing, or methotrexate dose reduction groups. The primary endpoint was a noninferiority of low disease activity maintenance at week 48 with a prespecified noninferiority margin of -18%. RESULTS: A total of 144 patients were analysed. The mean age was 58.2 years, 75.0% were female, and the mean CDAI was 2.70 with 61.8% in remission. The low disease activity at week 48 was 97.9% in the continued treatment group, 79.2% in the ozoralizumab spacing group (difference, -21.6; 95% CI, -39.9 to -5.7), and 72.7% in the methotrexate dose reduction group (difference, -30.4; 95% CI, -54.0 to -10.5). In the baseline remission subgroup, remission maintenance rates were comparable in the 3 groups (77.4%, 76.7%, 79.2%, respectively). No significant differences were demonstrated in changes in the Health Assessment Questionnaire Disability Index and modified total Sharp score. Adverse events occurred in 68.0%, 59.2%, and 58.0%, respectively. CONCLUSIONS: Treatment tapering may not be feasible in patients with low disease activity, whereas both extending the TNF inhibitor interval and reducing the methotrexate dose may be reasonable options for patients in remission.