Introduction: Efzofitimod was evaluated in an ascending dose study (3 cohorts - 1, 3, 5 mg/kg; 6 monthly doses) in patients with chronic pulmonary sarcoidosis (prednisone equivalent dose ?10 mg/day). Patients were randomized 1:2 (placebo:efzofitimod). Dose dependent improvements in steroid burden, FVC and patient reported outcomes (PROs) were noted [1]. We pooled data to gain precision and investigate novel definitions of responder analyses.

Methods: The placebo (n=12) and 1 mg/kg arm (n=8) were subtherapeutic and pooled. The 3 (n=8) and 5 mg/kg arm (n=9) were considered therapeutic and pooled. The analysis population remained the same. We compared the time to relapse (log rank test) for steroid use; random coefficient regression model with baseline adjustment to test the difference in slope for FVC (i.e. rate of change); and proportion of patients with changes that are multiples of the minimal clinically important difference (MCID) for PROs (KSQ-L).

Results: In the subtherapeutic group 54.4% of patients relapsed compared to 7.7% in the therapeutic group (p=0.017). The rate of change for FVC was significantly improved for the therapeutic group (p=0.035) compared to the subtherapeutic group. In the therapeutic group 9 patients (52.9%) showed increase ?12 for KSQ-L (3 times MCID) compared with 3 (15.0%) in the subtherapeutic group (p=0.032). Significant improvements were observed in several composite endpoints combining any taper in steroids without worsening in FVC or PROs.

Conclusions: These findings provide further evidence of efficacy for efzofitimod and initial proposals for responder endpoints in pulmonary sarcoidosis.

1. Culver DA et al. Chest. 2022 Nov 8;S0012-3692(22)04053-3