Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis–Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial
Dinesh Khanna, Celia J. F. Lin, Daniel E. Furst, Bridget K. Wagner, Mauro Zucchetto, Ganesh Raghu, Fernando J. Martínez, Jonathan Goldin, Jeffrey Siegel, Christopher P. Denton
Abstract
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).