Introduction: Pulmonary sarcoidosis often requires prolonged corticosteroid therapy despite cumulative toxicity and limited approved steroid-sparing options [1] . In chronic disease, reducing corticosteroid exposure while maintaining pulmonary stability remains a central goal [2] . XTMAB-16 is an investigational anti-TNFα being evaluated for pulmonary sarcoidosis [34] . XTMAB-16-201 Part A was a first-in-patient, dose-ranging study.

Objectives: To characterize cohort-level corticosteroid reduction, pulmonary stability, and background immunosuppressant exposure across XTMAB-16 regimens, and to support selection of 4 mg/kg every 4 weeks for further development.

Materials and Methods: Adults with chronic active pulmonary sarcoidosis receiving oral corticosteroids and second-line immunosuppressive therapy were randomized to placebo or XTMAB-16 2mg/kg Q4 weeks (W), 4mg/kg Q4W, 2mg/kg Q2W, or 4mg/kg Q2W in XTMAB-16-201 Part A (NCT05890729).Descriptive cohort-level analyses summarized corticosteroid reduction, pulmonary function, concomitant immunosuppressant use, exposure, and immunogenicity to further characterize regimen-level findings [4] .

Results: Thirty-nine participants were randomized; 37 completed Week 12. Baseline mean oral corticosteroid dose was 8.7, 9.4, 10.4, 8.0, and 10.4 mg/day in the placebo, 2mg/kg Q4W, 4mg/kg Q4W, 2mg/kg Q2W, or 4mg/kg Q2W cohorts, respectively. Complete steroid withdrawal was achieved by 4/11 (36%), 2/8 (25%), 4/7 (57%), 0/6 (0%), and 1/7 (14.3%) participants, respectively. Baseline mean FVC percent predicted was 97.4%, 80.0%, 87.7%, 79.7%, and 86.0% across the same cohorts.
Although corticosteroid withdrawal occurred in both placebo and active-treatment cohorts, pulmonary stability was more consistently maintained in XTMAB-16-treated participants, whereas placebo-treated participants demonstrated declines in FVC. Considering taper depth, steroid withdrawal, lung function stability, background therapy, exposure and immunogenicity, 4mg/kg Q4W demonstrated a balanced profile across steroid reduction, pulmonary stability, exposure, and immunogenicity.

Conclusions: XTMAB-16-201 Part A was not powered to establish efficacy. These descriptive cohort-level analyses supported selection of XTMAB-16 4mg/kg Q4W for continued development and highlight the importance of integrating corticosteroid reduction, pulmonary stability, and treatment context when evaluating potential steroid-sparing therapies in pulmonary sarcoidosis.