Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis–Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial

Abstract Rationale Tocilizumab, an anti–IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis (SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial. Objectives Assess long-term safety and efficacy of tocilizumab. Methods Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab). Measurements and Main Results Eighty-two of 107 patients in the placebo-tocilizumab group and 85 of 105 patients in the continuous-tocilizumab group completed 96 weeks. Mean age and disease duration were 48 years and 23 months; high-resolution computed tomography revealed ILD in 61%. Mean (95% confidence interval [CI]) change in modified Rodnan skin score from baseline to week 96 was −8.4 (−10.0 to −6.8) for placebo-tocilizumab and −9.6 (−10.9 to −8.4) for continuous-tocilizumab. Mean (95% CI) change in FVC (percent predicted) from baseline to week 96 was −3.3 (−5.1 to −1.5) for placebo-tocilizumab and −0.5 (−2.4 to 1.3) for continuous-tocilizumab among completers and, in a post hoc analysis, −4.1 (−6.7 to −1.6) and −0.6 (−3.1 to 2.0), respectively, among completers with ILD (mean [95% CI] change from Weeks 48 to 96: 0.9 [−0.8 to 2.7] and −0.4 [−2.3 to 1.5], respectively). Rates per 100 patient-years of serious adverse events from Weeks 48 to 96 were 14.8 for placebo-tocilizumab and 15.8 for continuous-tocilizumab. Conclusions Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).