Efficacy and safety of tofacitinib in treatment of pemphigus: a single-center cohort study

To evaluate the efficacy, safety, and steroid-sparing effect of tofacitinib combined with corticosteroids (CS) in pemphigus treatment. Clinical data from moderate pemphigus patients treated with CS monotherapy or CS plus tofacitinib (CT) between June 2019 and January 2024 were analyzed. The primary endpoint was complete remission (CR) rate at 1 year. Secondary endpoints comprised the monthly number of patients achieving the Minimum therapeutic dose of corticosteroids (CSmin) therapy, total annual cumulative CS doses, monthly median CS doses, relapse frequency, and adverse events (AEs). Transcriptomic profiling (RNA-sequencing), Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) were performed to assess JAK-STAT pathway activation. Twelve patients were enrolled in the CS group and 10 in the CT group. No significant difference in CR rates was observed (40.00% vs. 16.67%, P = 0.35), but the CT group demonstrated a 4.46-fold higher probability of achieving CR (HR = 4.46, P = 0.04). The CT group has more patients achieved CSmin, with lower cumulative (6,862.25 vs. 10,233 mg, P < 0.001) and median monthly CS doses. AEs incidence (70% vs. 41.67%, P = 0.35) and relapse rates (60% vs. 16.67%, P = 0.07) did not differ significantly. Transcriptomic and IF analyses confirmed JAK-STAT pathway hyperactivation in pemphigus lesions. Tofacitinib adjunct therapy demonstrated significant steroid-sparing benefits with comparable efficacy and safety to CS monotherapy in pemphigus, supported by mechanistic evidence of JAK-STAT pathway hyperactivation in pemphigus.