Long-term safety and efficacy of tocilizumab in adult-onset Still’s disease: open-label, long-term extension of the phase III trial

Abstract Objective To investigate the long-term safety and efficacy of tocilizumab, an interleukin-6 receptor inhibitor, in patients with adult-onset Still’s disease. Methods Patients who completed the precedent phase III trial of tocilizumab for adult-onset Still’s disease were enrolled in a long-term extension (LTE) study. Patients received intravenous tocilizumab (8 mg/kg every two weeks) until its approval in Japan. The primary end point was safety and tolerability, and secondary endpoints included the ACR coreset response, glucocorticoid doses, tocilizumab dosing interval, remission defined as achieving ACR50 without fever, and other laboratory parameters. Efficacy was assessed every 12 weeks. Results All 22 patients who had completed the precedent phase III trial participated in the LTE study. 16 (72.7%) completed the LTE study, with the mean observation period of 168.9 ± 10.8 weeks. Whereas three (13.6%) patients experienced serious adverse events, resulting in two patients withdrawn from the trial, no new safety signal was detected. Treatment efficacy was maintained through the LTE study, with the ACR70 response rate of 68.2% and 95.2% reduction in glucocorticoid doses from the start of the phase III trial and glucocorticoid-free remission of 40.9% at the last visit. Laboratory markers such as C-reactive protein and ferritin remained well controlled. The dosing interval was successfully extended in 63.6% of patients, with the overall mean tocilizumab interval at the final visit of 3.4 weeks. Conclusions During the observation period, no new safety findings were observed with the long-term use of tocilizumab. Response to tocilizumab was sustained even with an extended dosing interval, with substantial glucocorticoid dose reduction or discontinuation. Clinical trial registration UMIN000018414