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

• Published in: American journal of respiratory and critical care medicine Vol. 205; no. 6; pp. 674 - 684
• Main Authors: Khanna, Dinesh, Lin, Celia J F, Furst, Daniel E, Wagner, Bridget, Zucchetto, Mauro, Raghu, Ganesh, Martinez, Fernando J, Goldin, Jonathan, Siegel, Jeffrey, Denton, Christopher P
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 15.03.2022
• Subjects: Adult; Antibodies, Monoclonal, Humanized; Clinical trials; Double-Blind Method; Drugs; Humans; Lung diseases; Lung Diseases, Interstitial - complications; Lung Diseases, Interstitial - etiology; Monoclonal antibodies; Occupational safety; Placebo effect; Scleroderma; Scleroderma, Systemic - complications; Scleroderma, Systemic - drug therapy; Sclerosis; Treatment Outcome; Vital Capacity; lung diseases; respiratory function tests; biological therapy; interstitial; systemic scleroderma
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.202103-0714oc

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. Assess long-term safety and efficacy of tocilizumab. 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). 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 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. 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).