A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis

Abstract

Objectives: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; IL-6 antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis.

Methods: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In period 1, subjects were treated with open-label s.c. sarilumab 200 mg every 2 weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed period 1 without a sarcoidosis flare entered period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. The end points included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient-reported outcomes, and laboratory values.

Results: Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed period 1. During period 1, 4 of the 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of the 15 subjects (35.7%). During period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis.

Conclusion: In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal of improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn.

Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT04008069.

Keywords: IL-6; granulomatous disease; sarcoidosis; sarilumab.