Importance Cutaneous sarcoidosis (CS) is a chronic granulomatous skin disease associated with substantial morbidity and no approved therapies. Objective To evaluate the efficacy and safety of brepocitinib, an oral, selective, tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor, in adults with CS. Design, Setting, and Participants BEACON is an ongoing, global, multicenter, randomized, double-blind, placebo-controlled phase 2/3 trial. This prespecified interim analysis evaluated the 16-week, dose-ranging phase 2 portion of the study conducted between April 9, 2025, and July 18, 2025. Adults with biopsy-proven active CS were randomized 3:2:2 to receive brepocitinib, 45 mg; brepocitinib, 15 mg; or placebo once daily. Main Outcomes and Measures The primary efficacy outcome was change from baseline in the Cutaneous Sarcoidosis Activity and Morphology Instrument-Activity (CSAMI-A) score at week 16. Additional outcomes included achievement of Cutaneous Sarcoidosis Activity-Investigator Global Assessment (CSA-IGA) clear or almost clear with a 2 or greater category improvement, CSAMI-A response (≥50% relative improvement), 10-point or greater CSAMI-A score reduction, achievement of a CSAMI-A score less than 5, patient-reported outcomes, and safety. Results Thirty-one participants (mean [SD] age, 53.3 [9.6] years; 18 female individuals [58%] and 13 male individuals [42%]) were enrolled. Both brepocitinib doses achieved rapid, significant improvements in CS disease activity: by week 16, CSAMI-A scores improved by 22.3 points in the 45-mg group and 22.2 points in the 15-mg group compared with a 0.7-point improvement with placebo (P < .001). Across increasingly stringent responder-based and cutaneous remission-oriented end points, efficacy consistently favored brepocitinib, 45 mg, supporting a dose-dependent treatment effect. Compared with placebo, brepocitinib, 45 mg, resulted in higher rates of CSA-IGA clear or almost clear disease (69.2% vs 0%; P = .01), CSAMI-A response (76.9% vs 0%; P = .003), ≥10-point CSAMI-A reduction (100% vs 14.3%; P < .001), and achievement of a CSAMI-A score of less than 5 (61.5% vs 0%; P = .005). Clinical benefit extended to difficult to treat phenotypes, including lupus pernio, despite protocol-mandated systemic glucocorticoid discontinuation, and was accompanied by substantial improvements in skin-related quality of life. No deaths or serious adverse events occurred. Conclusions and Relevance In the phase 2 portion of the BEACON randomized clinical trial, brepocitinib produced rapid, dose-dependent, and clinically meaningful improvements in CS. As the first randomized, placebo-controlled trial to demonstrate efficacy of a targeted therapy in CS, these findings support selective TYK2/JAK1 inhibition as a potentially promising therapeutic strategy for CS and support ongoing phase 3 evaluation. Trial Registration ClinicalTrials.gov Identifier: NCT06978725.
Importance Cutaneous sarcoidosis (CS) is a chronic granulomatous skin disease associated with substantial morbidity and no approved therapies. Objective To evaluate the efficacy and safety of brepocitinib, an oral, selective, tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitor, in adults with CS. Design, Setting, and Participants BEACON is an ongoing, global, multicenter, randomized, double-blind, placebo-controlled phase 2/3 trial. This prespecified interim analysis evaluated the 16-week, dose-ranging phase 2 portion of the study conducted between April 9, 2025, and July 18, 2025. Adults with biopsy-proven active CS were randomized 3:2:2 to receive brepocitinib, 45 mg; brepocitinib, 15 mg; or placebo once daily. Main Outcomes and Measures The primary efficacy outcome was change from baseline in the Cutaneous Sarcoidosis Activity and Morphology Instrument–Activity (CSAMI-A) score at week 16. Additional outcomes included achievement of Cutaneous Sarcoidosis Activity–Investigator Global Assessment (CSA-IGA) clear or almost clear with a 2 or greater category improvement, CSAMI-A response (≥50% relative improvement), 10-point or greater CSAMI-A score reduction, achievement of a CSAMI-A score less than 5, patient-reported outcomes, and safety. Results Thirty-one participants (mean [SD] age, 53.3 [9.6] years; 18 female individuals [58%] and 13 male individuals [42%]) were enrolled. Both brepocitinib doses achieved rapid, significant improvements in CS disease activity: by week 16, CSAMI-A scores improved by 22.3 points in the 45-mg group and 22.2 points in the 15-mg group compared with a 0.7-point improvement with placebo ( P < .001). Across increasingly stringent responder-based and cutaneous remission–oriented end points, efficacy consistently favored brepocitinib, 45 mg, supporting a dose-dependent treatment effect. Compared with placebo, brepocitinib, 45 mg, resulted in higher rates of CSA-IGA clear or almost clear disease (69.2% vs 0%; P = .01), CSAMI-A response (76.9% vs 0%; P = .003), ≥10-point CSAMI-A reduction (100% vs 14.3%; P < .001), and achievement of a CSAMI-A score of less than 5 (61.5% vs 0%; P = .005). Clinical benefit extended to difficult to treat phenotypes, including lupus pernio, despite protocol-mandated systemic glucocorticoid discontinuation, and was accompanied by substantial improvements in skin-related quality of life. No deaths or serious adverse events occurred. Conclusions and Relevance In the phase 2 portion of the BEACON randomized clinical trial, brepocitinib produced rapid, dose-dependent, and clinically meaningful improvements in CS. As the first randomized, placebo-controlled trial to demonstrate efficacy of a targeted therapy in CS, these findings support selective TYK2/JAK1 inhibition as a potentially promising therapeutic strategy for CS and support ongoing phase 3 evaluation. Trial Registration ClinicalTrials.gov Identifier: NCT06978725
This case report describes 2 patients with tuberculosis verrucosa cutis complicated by chronic lymphedema diagnosed using targeted next-generation sequencing.
