Lung function preservation in a phase 3 trial of tocilizumab (TCZ) in systemic sclerosis (SSc)

Abstract

Background: Anti–interleukin-6 receptor antibody TCZ showed clinically relevant lung function preservation (forced vital capacity [FVC]) in SSc patients (pts) in a phase 2 trial. Objective: Investigate TCZ vs placebo (PBO) in SSc in a phase 3 trial. Methods: Pts were randomized 1:1 to double-blind subcutaneous TCZ 162 mg or PBO per week (wk) for 48 wks. Primary endpoint: difference (TCZ vs PBO) in modified Rodnan skin score (mRSS) change from baseline (∆BL). Secondary endpoints: percent-predicted (pp)FVC; time to treatment failure (TTF; time from first study treatment to first occurrence of death, FVC decline >10%, mRSS increase ≥20% and mRSS ≥5, or occurrence of SSc complications); Health Assessment Questionnaire–Disability Index (HAQ-DI); pt/physician global assessment (Pt/PhGA) visual analog scale. Results: Of 106 PBO and 104 TCZ pts, 31% had previous/current interstitial lung disease based on their history. At wk 48, adjusted least-squares mean difference ∆BL mRSS PBO vs TCZ was –1.7 [95% CI: –3.8, 0.3], p=0.098). Cumulative distribution of ∆BL ppFVC (median [IQR] PBO –3.9 [–7.2, 0.6]; TCZ –0.6 [–5.3, 3.9] van Elteren nominal p=0.0015) and difference in mean ∆BL FVC at wk 48 (167 mL [95% CI: 83, 250]) favored TCZ. TTF hazard ratio (95% CI) was 0.6 (0.4, 1.1) numerically favoring TCZ (Cox proportional hazards p=0.082). No clinically meaningful difference was seen in mean (95% CI) difference ∆BL HAQ-DI –0.1 (–0.2, 0.1), PtGA –2.4 (–8.6, 3.7), PhGA –2.5 (–8.7, 3.8). Safety profile was consistent with SSc complications and TCZ treatment. Conclusion: The primary mRSS endpoint was not met. A clinically relevant difference in FVC was seen for TCZ vs PBO, with preservation of lung function.