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      Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis

      systematic-review

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          Abstract

          We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata (AA). 13 trials totaling 3,613 patients were included. Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA. Ranking analysis suggested that brepocitinib 30mg has the best relative effect in reducing the SALT score (sucra = 0.9831), and demonstrated comparable efficacy to deuruxolitinib 12mg (sucra = 0.9245), followed by deuruxolitinib 8mg (sucra = 0.7736). Regarding the SALT 50 response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690). For achieving the SALT 75 response, deuruxolitinib 12mg had the highest probability (sucra = 0.9761), followed by deuruxolitinib 8mg (sucra = 0.8678) and brepocitinib 30mg (sucra = 0.8448). Deuruxolitinib 12mg might be the most effective therapy for patients with severe AA (sucra = 0.9395), followed by ritlecitinib 50mg (sucra = 0.8753) and deuruxolitinib 8mg (sucra = 0.8070). Deuruxolitinib 12mg/8mg demonstrated notable efficacy for moderate-to-severe AA, and is expected to be a new treatment option for AA. It was worth noting that deuruxolitinib exhibit a greater likelihood of causing adverse events in comparison to other JAK inhibitors. Ritlecitinib 50mg seemed to exhibit fewer adverse effects in the high-dose groups of oral JAK inhibitors and might be an optimal choice to balance safety and efficacy. The majority of JAK inhibitors exhibited acceptable short-term safety profiles. To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed.

          Systematic Review Registration: identifier [CRD42022368012].

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          Most cited references45

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          Alopecia areata investigational assessment guidelines--Part II. National Alopecia Areata Foundation.

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            Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis.

            Alopecia areata (AA) is a common, inflammatory, nonscarring type of hair loss. Significant variations in the clinical presentation of AA have been observed, ranging from small, well-circumscribed patches of hair loss to a complete absence of body and scalp hair. Patients affected by AA encompass all age groups, sexes, and ethnicities, and may experience frustration with the unpredictable nature of their disease for which there is currently no definitive treatment. The cause of AA remains incompletely understood, though it is believed to result-at least in part-from a loss of immune privilege in the hair follicle, autoimmune-mediated hair follicle destruction, and the upregulation of inflammatory pathways. Patients with AA frequently experience marked impairment in psychological well-being, self-esteem, and may be more likely to suffer from psychiatric comorbidities. Part one of this two-part continuing medical education series describes the epidemiology, clinical evaluation, prognosis, and recent advancements in the understanding of the pathogenesis of AA.
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              Alopecia areata.

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                Author and article information

                Contributors
                Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2372930/overviewRole: Role: Role:
                URI : https://loop.frontiersin.org/people/1242437/overviewRole: Role:
                URI : https://loop.frontiersin.org/people/2634041/overviewRole: Role: Role:
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                10 April 2024
                2024
                : 15
                : 1372810
                Affiliations
                [1] 1 Department of Pharmacy , Sichuan Provincial People’s Hospital , School of Medicine , University of Electronic Science and Technology of China , Chengdu, Sichuan, China
                [2] 2 Personalized Drug Therapy Key Laboratory of Sichuan Province , University of Electronic Science and Technology of China , Chengdu, Sichuan, China
                [3] 3 Departments of Nuclear Medicine , Sichuan Provincial People’s Hospital , School of Medicine , University of Electronic Science and Technology of China , Chengdu, Sichuan, China
                Author notes

                Edited by: Ahmed H. E. Hassan, Mansoura University, Egypt

                Reviewed by: Zoran Todorovic, University of Belgrade, Serbia

                Hisayoshi Imanishi, Osaka Metropolitan University, Japan

                *Correspondence: Nan Liu, liunan_815@ 123456163.com
                Article
                1372810
                10.3389/fphar.2024.1372810
                11039836
                38659584
                8d385ae5-30ef-4894-b271-cc309a67795c
                Copyright © 2024 Yan, Wang, Tang and Liu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 January 2024
                : 20 March 2024
                Funding
                The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Popularization and Application of Medical Research Projects of Sichuan Provincial Health and Wellness Commission (19PJ136).
                Categories
                Pharmacology
                Systematic Review
                Custom metadata
                Inflammation Pharmacology

                Pharmacology & Pharmaceutical medicine
                alopecia areata,jak inhibitors,network meta-analysis,rct,efficacy,safety

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