JAK/STAT Inhibitors Reduce Risk of New-Onset Keloids and Hypertrophic Scars: A Multi-Center Retrospective Cohort Study
September 2026 | Volume 25 | Issue 9 | 779 | Copyright © September 2026
Published online August 29, 2026
Robert Adler BAa, Fariha Ahmed BAa, Michael Kozlov BAa, Navid Ashrafi MPHa,b, Neal Gupta MDc, Manan D. Mehta MDc, Katerina Svigos MDc, Jessica L. Feig MD PhDc,d, Jared R. Jagdeo MD MSc,d
aCollege of Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY
bSchool of Public Health, State University of New York, Downstate Health Sciences University, Brooklyn, NY
cDepartment of Dermatology, State University of New York, Downstate Health Sciences University, Brooklyn, NY
dDermatology Service, Veterans Affairs New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, NY
Abstract
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.
INTRODUCTION
Keloids and hypertrophic scars are benign fibroproliferative skin disorders characterized by excessive and disorganized collagen deposition extending beyond the original wound margins, typically arising after cutaneous injury, surgery, inflammation, or acneiform eruptions.1 They disproportionately affect individuals with darker skin phototypes and commonly occur in anatomically high-tension areas such as the chest, shoulders, earlobes, and jawline.2 Clinically, keloids and hypertrophic scars may cause pruritus, pain, and significant cosmetic disfigurement, leading to substantial psychosocial burden and reduced quality of life.3 Histopathologically, keloids and hypertrophic scars demonstrate aberrant fibroblast proliferation, excessive extracellular matrix accumulation, and altered cytokine signaling, suggesting a complex interplay between mechanical forces, genetic susceptibility, and immune dysregulation.4 Despite their benign nature, keloids and hypertrophic scars remain a major therapeutic challenge due to their unpredictable behavior and tendency toward aggressive recurrence.5
Current treatment modalities for keloids and hypertrophic scars include surgical excision, intralesional corticosteroids, radiotherapy, cryotherapy, laser therapy, silicone-based occlusion, and topical or intralesional chemotherapeutic agents, often used in combination.2,4,5 However, no universally
