A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis

Abstract

Background Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed benefcial efects in GCA, leading to its approval. This study investigated the efcacy and safety of sarilumab (another IL-6Ri) in GCA. Methods This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200+26W) or 150 mg (SAR150+26W) with a 26-week GC taper, or placebo with a 52-week (PBO+52W) or 26-week (PBO+26W) GC taper. The primary efcacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized. Results Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n=6/13) of patients in SAR200+26W, 43% (n=3/7) in SAR150+26W, 30% (n=3/10) in PBO+52W, and 0 (n=0/6) in PBO+26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR defnition, showed similar results for SAR groups, but 60% (n=6/10) in PBO+52W and 17% (n=1/6) in PBO+26W taper groups achieved SR at week 52. Similar fndings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n=6/13, SAR200+26W), 43% (n=3/7, SAR150+26W), 60% (n=6/10, PBO+52W), and 33% (n=2/6, PBO+26W). The median actual cumulative GC dose received in the SAR200+26W group was lower than other groups. Most patients (80– 100%) experienced treatment-emergent adverse events, with similar incidences reported across groups. Conclusions Owing to the small sample size due to the early termination, it is difcult to draw clear conclusions from this study. There were no unexpected safety findings.