SYSTEMATIC REVIEW OF ORAL JANUS KINASE INHIBITORS IN ALOPECIA AREATA: INSIGHTS FROM 2020 TO 2025 STUDIES
Abstract
Background: Alopecia areata (AA) is an autoimmune, non-scarring hair loss disorder with variable clinical presentations. Its pathogenesis involves immune privilege collapse of the hair follicle, CD8+ T-cell activation, and cytokine signaling—particularly IFN-γ and IL-15—via the JAK/STAT pathway. Recent studies highlight Janus kinase (JAK) inhibitors as promising therapeutic agents for moderate-to-severe AA.
Objectives: This systematic review aimed to evaluate the efficacy and safety of oral JAK inhibitors in the treatment of adolescent and adult patients with AA based on studies published between 2020 and 2025.
Material and Methods: Following PRISMA 2020 guidelines, a comprehensive search of PubMed, Cochrane Library, and ClinicalTrials.gov was conducted for studies assessing oral JAK inhibitors (e.g., baricitinib, ritlecitinib, deuruxolitinib) in AA. Inclusion criteria encompassed RCTs, observational studies, and interventional trials involving patients ≥12 years old with moderate-to-severe AA.
Results: Ten studies met the criteria, including seven RCTs. Efficacy was measured predominantly by the Severity of Alopecia Tool (SALT) score. Baricitinib and deuruxolitinib consistently demonstrated superior outcomes compared to placebo and traditional therapies, with up to 41.5% of patients achieving SALT ≤20 at 24 weeks. Long-term data confirmed sustained benefits. Adverse events were mostly mild (e.g., URTI, headache, acne); serious events and discontinuations were rare.
Conclusions: Oral JAK inhibitors represent an effective and generally well-tolerated option for treating moderate-to-severe AA. Their targeted mechanism offers advantages over traditional immunosuppressants, and accumulating long-term data support their integration into therapeutic guidelines.
References
Strazzulla, L. C., Wang, E. H. C., Avila, L., Lo Sicco, K., Brinster, N., Christiano, A. M., & Shapiro, J. (2018). Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis. Journal of the American Academy of Dermatology, 78(1), 1–12. https://doi.org/10.1016/j.jaad.2017.04.1141
Lee, H. H., Gwillim, E., Patel, K. R., Hua, T., Rastogi, S., Ibler, E., & Silverberg, J. I. (2020). Epidemiology of alopecia areata, ophiasis, totalis, and universalis: A systematic review and meta-analysis. Journal of the American Academy of Dermatology, 82(3), 675–682. https://doi.org/10.1016/j.jaad.2019.08.032
Abarca, Y. A., Scott-Emuakpor, R., Tirth, J., Moroz, O., Thomas, G. P., Yateem, D., & Alhusayen, R. (2025). Alopecia areata: Understanding the pathophysiology and advancements in treatment modalities. Cureus, 17(1), e78298. https://doi.org/10.7759/cureus.78298
Sterkens, A., Lambert, J., & Bervoets, A. (2021). Alopecia areata: A review on diagnosis, immunological etiopathogenesis and treatment options. Clinical and Experimental Medicine, 21(2), 215–230. https://doi.org/10.1007/s10238-020-00673-w
Zhou, C., Li, X., Wang, C., & Zhang, J. (2021). Alopecia areata: An update on etiopathogenesis, diagnosis, and management. Clinical Reviews in Allergy and Immunology, 61(3), 403–423. https://doi.org/10.1007/s12016-021-08883-0
Lensing, M., & Jabbari, A. (2022). An overview of JAK/STAT pathways and JAK inhibition in alopecia areata. Frontiers in Immunology, 13, 955035. https://doi.org/10.3389/fimmu.2022.955035
Park, H., Yu, D. A., & Kwon, O. (2019). Janus kinase inhibitors: An innovative treatment for alopecia areata. Journal of Dermatology, 46(8), 724–730. https://doi.org/10.1111/1346-8138.14986
Barati Sedeh, F., Michaelsdóttir, T. E., Henning, M. A. S., Jemec, G. B. E., & Ibler, K. S. (2023). Comparative efficacy and safety of Janus kinase inhibitors used in alopecia areata: A systematic review and meta-analysis. Acta Dermato-Venereologica, 103, adv00855. https://doi.org/10.2340/actadv.v103.4536
Shah, R. J., Banerjee, S., Raychaudhuri, S., & Raychaudhuri, S. P. (2023). JAK-STAT inhibitors in immune mediated diseases: An overview. Indian Journal of Dermatology, Venereology and Leprology, 89(5), 691–699. https://doi.org/10.25259/IJDVL_1152_2022
Favoino, E., Prete, M., Catacchio, G., Ruscitti, P., Navarini, L., Giacomelli, R., & Perosa, F. (2021). Working and safety profiles of JAK/STAT signaling inhibitors: Are these small molecules also smart? Autoimmunity Reviews, 20(3), 102750. https://doi.org/10.1016/j.autrev.2021.102750
Rakowska, A., Rudnicka, L., Olszewska, M., Bergler-Czop, B., Czuwara, J., Brzezińska-Wcisło, L., & Adamski, Z. (2023). Alopecia areata: Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Part 2: Treatment. Dermatology Review, 110(2), 101–120. https://doi.org/10.5114/dr.2023.127811
Dash, P. S., Khondker, L., Khan, M. A., Talukder, M. S., Jahan, S., & Lubna, E. K. (2025). Comparison of efficacy of baricitinib versus methotrexate therapy in the treatment of severe alopecia areata. Journal of Population Therapeutics and Clinical Pharmacology, 32(3), 402–411. https://doi.org/10.53555/9n99h371
Vignoli, C. A., Gargiulo, L., Ibba, L., Balato, A., Barbareschi, M., Barruscotti, S., & Pellacani, G. (2025). Baricitinib for the treatment of severe alopecia areata: Results from a 52-week multicenter retrospective real-world study. Journal of Dermatological Treatment, 36(1), 2444494. https://doi.org/10.1080/09546634.2024.2444494
Mesinkovska, N., King, B., Zhang, X., Guttman-Yassky, E., Magnolo, N., Sinclair, R., & Senna, M. (2024). Efficacy and safety of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, in adolescent and adult patients with alopecia totalis and alopecia universalis. Journal of Dermatology, 51(11), 1414–1424. https://doi.org/10.1111/1346-8138.17442
King, B., Senna, M. M., Mesinkovska, N. A., Lynde, C., Zirwas, M., Maari, C., & Guttman-Yassky, E. (2024). Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: Results from the phase 3 randomized, controlled trial (THRIVE-AA1). Journal of the American Academy of Dermatology, 91(5), 880–888. https://doi.org/10.1016/j.jaad.2024.06.097
Senna, M., Mostaghimi, A., Ohyama, M., Sinclair, R., Dutronc, Y., Wu, W. S., & King, B. (2024). Long-term efficacy and safety of baricitinib in patients with severe alopecia areata: 104-week results from BRAVE-AA1 and BRAVE-AA2. Journal of the European Academy of Dermatology and Venereology, 38(3), 583–593. https://doi.org/10.1111/jdv.19665
Kwon, O., Senna, M. M., Sinclair, R., Ito, T., Dutronc, Y., Lin, C. Y., & King, B. (2023). Efficacy and safety of baricitinib in patients with severe alopecia areata over 52 weeks of continuous therapy in two phase III trials (BRAVE-AA1 and BRAVE-AA2). American Journal of Clinical Dermatology, 24(3), 443–451. https://doi.org/10.1007/s40257-023-00764-w
King, B., Mesinkovska, N., Mirmirani, P., Bruce, S., Kempers, S., Guttman-Yassky, E., & Sinclair, R. (2022). Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus kinase inhibitor, in moderate-to-severe alopecia areata. Journal of the American Academy of Dermatology, 87(2), 306–313. https://doi.org/10.1016/j.jaad.2022.03.045
King, B., Guttman-Yassky, E., Peeva, E., Banerjee, A., Sinclair, R., Pavel, A. B., & Zangrilli, J. G. (2021). A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. Journal of the American Academy of Dermatology, 85(2), 379–387. https://doi.org/10.1016/j.jaad.2021.03.050
Concert Pharmaceuticals, Inc. (2021). Protocol CP543.3002: A double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of CTP-543 in adult patients with moderate to severe alopecia areata. Concert Pharmaceuticals, Inc.
Institute of Dermatology, Thailand. (2019). Effectiveness and safety of tofacitinib in patients with extensive and recalcitrant alopecia areata. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03800979
Rakowska, A., Rudnicka, L., Olszewska, M., Bergler-Czop, B., Czuwara, J., Brzezińska-Wcisło, L., & Adamski, Z. (2023). Alopecia areata: Diagnostic and therapeutic recommendations of the Polish Dermatological Society. Part 1: Diagnosis and severity assessment. Dermatology Review, 110(2), 89–100. https://doi.org/10.5114/dr.2023.127704
Stefanis, A. J., Dolezal, T., Gkalpakiotis, S., & Arenberger, P. (2025). Comparative efficacy and safety of baricitinib against traditional therapies in severe alopecia areata: A retrospective cohort study. Journal of Cosmetic Dermatology, 24(2), e16666. https://doi.org/10.1111/jocd.16666
Almutairi, N., Nour, T. M., & Hussain, N. H. (2019). Janus kinase inhibitors for the treatment of severe alopecia areata: An open-label comparative study. Dermatology, 235(2), 130–136. https://doi.org/10.1159/000494613
Gupta, A. K., Bamimore, M. A., Mirmirani, P., Piguet, V., & Talukder, M. (2025). The relative efficacy and safety of monotherapies for alopecia areata: A network meta-analysis study. Journal of Cosmetic Dermatology, 24(4), e70185. https://doi.org/10.1111/jocd.70185
Gregoire, S., McIntosh, B., Sanchez, K., Biba, U., & Mostaghimi, A. (2025). Local corticosteroids for alopecia areata: A narrative review. Dermatology and Therapy, 15(7), 1607–1631. https://doi.org/10.1007/s13555-025-01421-2
Liu, Z., & Liu, X. (2023). Gut microbiome, metabolome and alopecia areata. Frontiers in Microbiology, 14, 1281660. https://doi.org/10.3389/fmicb.2023.1281660
Sánchez-Pellicer, P., Navarro-Moratalla, L., Núñez-Delegido, E., Agüera-Santos, J., & Navarro-López, V. (2022). How our microbiome influences the pathogenesis of alopecia areata. Genes, 13(10), 1860. https://doi.org/10.3390/genes13101860
Carrington, A. E., Maloh, J., Nong, Y., Agbai, O. N., Bodemer, A. A., & Sivamani, R. K. (2023). The gut and skin microbiome in alopecia: Associations and interventions. Journal of Clinical and Aesthetic Dermatology, 16(10), 59–64.
Mahmud, M. R., Akter, S., Tamanna, S. K., Mazumder, L., Esti, I. Z., Banerjee, S., & Rahman, M. M. (2022). Impact of gut microbiome on skin health: Gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes, 14(1), 2096995. https://doi.org/10.1080/19490976.2022.2096995
Solimani, F., Meier, K., & Ghoreschi, K. (2019). Emerging topical and systemic JAK inhibitors in dermatology. Frontiers in Immunology, 10, 2847. https://doi.org/10.3389/fimmu.2019.02847
Bokhari, L., & Sinclair, R. (2018). Treatment of alopecia universalis with topical Janus kinase inhibitors: A double blind, placebo, and active controlled pilot study. International Journal of Dermatology, 57(12), 1464–1470. https://doi.org/10.1111/ijd.14192
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