JAK/STAT Inhibitors Reduce Risk of New-Onset Keloids and Hypertrophic Scars: A Multi-Center Retrospective Cohort Study

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BACKGROUND: Keloids and hypertrophic scars are fibroproliferative skin disorders characterized by excessive collagen deposition and high recurrence rates despite existing therapies. Emerging evidence implicates immune-mediated pathways, including Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, in their pathogenesis. However, population-level data evaluating the association between JAK inhibitor exposure and keloid/hypertrophic scar risk are lacking. OBJECTIVE: To evaluate whether initiation of JAK inhibitors is associated with a reduced risk of incident hypertrophic scar or keloid formation. METHODS: Using a target trial emulation framework, we conducted a retrospective cohort study within the TriNetX US Collaborative Network. Adults without prior hypertrophic scar or keloid formation were classified as initiators of a JAK inhibitor or psoriasis comparators without JAK inhibitor exposure. Propensity score matching (1:1) balanced demographic characteristics, comorbidities, healthcare utilization, trauma history, and surgical exposure. The primary outcome was incident hypertrophic scar or keloid formation (ICD-10-CM L91.0) within 730 days. Risk ratios (RRs) and Cox proportional hazards models were used to estimate cumulative and time-to-event associations. RESULTS: After matching, 122,341 individuals were included in each group. Within two years, hypertrophic scar or keloid formation occurred in 0.14% of JAK inhibitor initiators versus 0.22% of comparators (RR 0.65, 95% CI 0.54-0.79; absolute risk difference -0.08%; P<0.001). JAK inhibitor initiation was also associated with a lower hazard of scar formation (HR 0.77, 95% CI 0.64-0.93). CONCLUSION: Initiation of JAK inhibitors was associated with a significantly reduced risk of incident hypertrophic scar or keloid formation. These findings support a potential role for JAK/STAT pathway modulation in keloid prevention and warrant prospective investigation. .

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