Real-World Safety of Janus Kinase Inhibitors in Alopecia Areata: A Propensity Score-Matched Cohort Study of a Global Federated Health Network
- 1Department of Dermatology, Research and Development Centre, Regional Specialist Hospital, Kamieńskiego 73a, 51-124 Wroclaw, Poland
- 2Division of Dermatology, Venereology and Clinical Immunology, Faculty of Medicine, Wroclaw University of Science and Technology, Wybrzeże Stanisława Wyspiańskiego 27, 50-370 Wroclaw, Poland
- 3Department of Dermatovenereology, 4th Military Hospital, Rudolfa Weigla 5, 50-981 Wroclaw, Poland
Abstract
Background/Objectives: Janus kinase inhibitors (JAKis) have transformed the treatment of alopecia areata (AA), but pivotal trials had short follow-ups and real-world long-term safety data remain scarce. We compared incident adverse outcomes between patients with AA exposed and not exposed to JAKis. Methods: In this retrospective cohort study of the TriNetX Global Collaborative Network, adults (≥18 years) with ≥2 diagnoses of AA (ICD-10-CM L63) and ≥2 medication events for baricitinib, tofacitinib, ritlecitinib, or oral ruxolitinib were matched 1:1 by propensity score on demographics and 13 comorbidities to patients with AA and no recorded exposure to these agents. Cox models estimated hazard ratios (HRs); p values for the 19 estimable outcomes were adjusted using the Benjamini–Hochberg procedure (false discovery rate 5%), and E-values assessed unmeasured confounding. Drug-specific and eight sensitivity analyses were performed. Results: Matching yielded 1771–1805 patients per cohort, depending on the outcome domain. Acne was more frequent with JAKis (HR, 2.425; 95% CI, 1.838–3.200; q < 0.001) in all analyses, including versus conventional immunosuppressants (HR, 1.688; 95% CI, 1.321–2.157), whereas upper respiratory tract infections (HR, 0.620; 95% CI, 0.476–0.808; q = 0.004) and urinary tract infections (HR, 0.458; 95% CI, 0.290–0.724; q = 0.006) were recorded less frequently. Cutaneous cancer was more frequent (HR, 2.639; 95% CI, 1.322–5.270; q = 0.024) and persisted after 30- and 180-day latency periods but was attenuated under a fixed 2-year follow-up and after exclusion of other JAKi indications. Severe infections, herpes zoster, and autoimmune and psychiatric outcomes did not differ significantly. Conclusions: In real-world AA care, JAKis were not associated with a statistically significant increase in severe infections or incident psychiatric outcomes, although power for rare serious outcomes was limited. Acne was the most consistent adverse-event signal, whereas the cutaneous cancer finding was not fully robust across specifications and requires confirmation.
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BibTeX
@article{lysek2026realworld,
title = {{Real-World Safety of Janus Kinase Inhibitors in Alopecia Areata: A Propensity Score-Matched Cohort Study of a Global Federated Health Network}},
author = {Mateusz Łysek and Beata Jastrząb-Miśkiewicz and Piotr K. Krajewski},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207825},
url = {https://www.mdpi.com/2077-0383/15/20/7825},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Real-World Safety of Janus Kinase Inhibitors in Alopecia Areata: A Propensity Score-Matched Cohort Study of a Global Federated Health Network
AU - Mateusz Łysek
AU - Beata Jastrząb-Miśkiewicz
AU - Piotr K. Krajewski
PY - 2026
DA - 2026/10/10
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207825
UR - https://www.mdpi.com/2077-0383/15/20/7825
AB - Background/Objectives: Janus kinase inhibitors (JAKis) have transformed the treatment of alopecia areata (AA), but pivotal trials had short follow-ups and real-world long-term safety data remain scarce. We compared incident adverse outcomes between patients with AA exposed and not exposed to JAKis. Methods: In this retrospective cohort study of the TriNetX Global Collaborative Network, adults (≥18 years) with ≥2 diagnoses of AA (ICD-10-CM L63) and ≥2 medication events for baricitinib, tofacitinib, ritlecitinib, or oral ruxolitinib were matched 1:1 by propensity score on demographics and 13 comorbidities to patients with AA and no recorded exposure to these agents. Cox models estimated hazard ratios (HRs); p values for the 19 estimable outcomes were adjusted using the Benjamini–Hochberg procedure (false discovery rate 5%), and E-values assessed unmeasured confounding. Drug-specific and eight sensitivity analyses were performed. Results: Matching yielded 1771–1805 patients per cohort, depending on the outcome domain. Acne was more frequent with JAKis (HR, 2.425; 95% CI, 1.838–3.200; q < 0.001) in all analyses, including versus conventional immunosuppressants (HR, 1.688; 95% CI, 1.321–2.157), whereas upper respiratory tract infections (HR, 0.620; 95% CI, 0.476–0.808; q = 0.004) and urinary tract infections (HR, 0.458; 95% CI, 0.290–0.724; q = 0.006) were recorded less frequently. Cutaneous cancer was more frequent (HR, 2.639; 95% CI, 1.322–5.270; q = 0.024) and persisted after 30- and 180-day latency periods but was attenuated under a fixed 2-year follow-up and after exclusion of other JAKi indications. Severe infections, herpes zoster, and autoimmune and psychiatric outcomes did not differ significantly. Conclusions: In real-world AA care, JAKis were not associated with a statistically significant increase in severe infections or incident psychiatric outcomes, although power for rare serious outcomes was limited. Acne was the most consistent adverse-event signal, whereas the cutaneous cancer finding was not fully robust across specifications and requires confirmation.
SN - 2077-0383
ER -