LAUSR

OBJECTIVE To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. METHODS Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI] ≤10) for ≥12 weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12 weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score >10 or intervention with rescue treatments for any reason even if the CDAI score was ≤10. The impact of baseline characteristics on disease flare at week 64 (52 weeks after methotrexate discontinuation) was assessed with logistic regression models. RESULTS Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6 - 81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4 weeks, or subcutaneously every 2 weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72-83.80) were independent predictors of disease flare. CONCLUSION Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. TRIAL REGISTRATION NUMBER jRCTs041180071, UMIN000021247.