Treatment of alopecia areata with JAK inhibitors: a review of the literature Jaiden Townsend 1 , Aleksandar Godic 2,3 ✉ 1 UCL Medical School, London, UK. 2 The Harley Street Dermatology Clinic, London, UK. 3 Clapham Park Dermatology, London, UK. 117 2025;34:117-120 doi: 10.15570/actaapa.2025.22 Introduction Alopecia areata (AA) is a chronic autoimmune dermatologic condi- tion characterized by non-scarring hair loss that typically presents as discrete, well-circumscribed patches on the scalp or beard; a rare variant is diffuse hair loss. In more extensive phenotypes, the disease may progress to alopecia totalis (complete scalp hair loss) or alopecia universalis (total body hair loss). Although AA is not physically debilitating, its impact on quality of life, particularly among pediatric and young adult populations, can be profound, contributing to significant psychological distress and psychiatric comorbidity (1). The therapeutic landscape for AA has historically been limited to non-specific immunomodulatory strategies. Commonly em- ployed treatments include topical and systemic corticosteroids, intralesional steroid injections, topical calcineurin inhibitors (e.g., tacrolimus and pimecrolimus), contact immunotherapy, phototherapy, and systemic immunosuppressants such as metho- trexate or cyclosporin (2). Although combination regimens (e.g., corticosteroids with cyclosporin) may provide enhanced efficacy, outcomes remain variable, and relapse rates are high following cessation of therapy (3). For patients with extensive or treatment- refractory disease, durable regrowth remains elusive, underscor- ing the need for more targeted therapeutic modalities. Recent advances in the understanding of AA pathophysiology have implicated the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway as central drivers of dis- ease. Cytotoxic CD8 + NKG2D + T cells targeting anagen hair follicles release interferon-γ and interleukin-15, perpetuating follicular inflammation via JAK-dependent signaling (4). Both pan-JAK and selective JAK3 inhibition have demonstrated efficacy in reversing AA in preclinical murine models, establishing proof of concept for JAK inhibition in this context (4, 5). JAK inhibitors modulate inflammatory pathways by interfer- ing with type I and II cytokine signaling, suppressing T cell and natural killer cell activity, and attenuating the interferon-mediated response (5). Clinical data on JAK inhibitors in AA are rapidly ac- cumulating, with multiple agents, most notably baricitinib, ritl- ecitinib, and deuruxolitinib, demonstrating significant efficacy in phase 2 and 3 trials (6). These agents offer a promising alternative for patients with moderate to severe disease, with emerging evi- dence supporting sustained hair regrowth in a substantial propor- tion of patients. However, the therapeutic use of JAK inhibitors necessitates con- sideration of safety. Frequently reported adverse events include upper respiratory tract infections, acne, herpes simplex reactiva- tion, nasopharyngitis, hyperlipidemia, elevated creatine kinase, and scalp folliculitis (6). Long-term safety data are still evolving, and the risks of immunosuppression and potential thromboem- bolic or malignancy-related sequelae warrant ongoing vigilance. This review critically appraises the immunopathogenesis of AA, evaluates the current clinical evidence surrounding JAK inhib- itor use, and considers the therapeutic potential and limitations of these agents within clinical dermatology. Discussion JAK inhibitors have emerged as the most promising systemic ther- apy for moderate to severe AA. These small molecules (e.g., baric- itinib, ritlecitinib, deuruxolitinib, and tofacitinib) target the JAK- STAT pathway that drives the autoimmune attack on hair follicles. Recent phase 3 trials have demonstrated that oral JAK inhibitors produce significantly greater hair regrowth than placebo in adults (and adolescents) with ≥ 50% scalp hair loss. For example, in the two pivotal BRAVE-AA trials of baricitinib (a JAK1/2 inhibitor) in severe AA (combined n = 654; 18–70 years old), 38.8% of patients on the 4 mg dose (n = 219) of baricitinib achieved a Severity of Alopecia Tool (SALT) score ≤ 20 (≤ 20% scalp hair loss) by week 36, versus only 6.2% on placebo (n = 222). The lower 2 mg dose (n = 213) also beat placebo (22.8% versus 6.2% responders) but was Abstract Alopecia areata (AA) is chronic autoimmune non-scarring hair loss, which can progress to alopecia totalis or universalis. Conven- tional treatments, such as corticosteroids and immunotherapies, often offer limited temporary benefits in moderate to severe cas- es. Recent advances have identified Janus kinase (JAK) inhibitors as a promising therapeutic option, targeting cytokine pathways involved in AA pathogenesis. This review explores the current evidence surrounding JAK inhibitors in the management of AA. Clini- cal trials and case series have demonstrated notable efficacy in promoting hair regrowth, even in extensive disease. Baricitinib and deuruxolitinib have shown particularly strong results, with significant scalp hair regrowth and acceptable safety profiles. Common adverse effects include acne, elevated lipid levels, and mild laboratory abnormalities, although long-term data remain limited. This review summarizes the mechanisms, efficacy outcomes, and safety data of various JAK inhibitors used in AA and highlights the need for further research to establish optimal dosing, treatment duration, and long-term safety. Keywords: alopecia, alopecia areata, dermatology, hair disorder, JAK Acta Dermatovenerologica Alpina, Pannonica et Adriatica Acta Dermatovenerol APA Received: 18 June 2025 | Returned for modification: 28 July 2025 | Accepted: 31 July 2025 ✉ Corresponding author: aleksandar.godic@gmail.com 118 Acta Dermatovenerol APA | 2025;34:117-120 J. Townsend et al. less effective than 4 mg (7). Similarly, a multinational trial of ritl- ecitinib (a selective JAK3/TEC inhibitor) in patients ≥ 12 years old (n = 718; 12–75 years old) reported that 50 mg once daily (n = 239) led to 36.5% achieving SALT ≤ 20 at week 24, compared to 7.4% of the placebo recipients (n = 240), or a difference of 29.1% (8). In the recent THRIVE-AA1 trial of deuruxolitinib (a JAK1/2 inhibitor), in adults (n = 540; 18–65 years old) 29.6% of patients on 8 mg twice daily (n = 180) and 41.5% on 12 mg twice daily (n = 180) reached SALT ≤ 20 at 24 weeks, compared to only 0.8% with placebo pa- tients (n = 180) (9). In all these studies, secondary endpoints (e.g., higher SALT thresholds, quality-of-life scores, and patient satis- faction) also favored the active drug. Notably, extension data show that responders tend to maintain benefit over time; in the barici- tinib trials, over 90% of responders (n = 188) still had SALT ≤ 20 at week 104 (10). In contrast, earlier off-label use of tofacitinib (a JAK1/3 inhibitor) in severe AA was supported only by case series, and pooled analyses suggest that 54% of such patients achieved substantial regrowth (11). However, no large placebo-controlled trials exist for tofacitinib in this setting (see Fig. 1). These efficacy findings are reinforced by recent meta-analyses. A 2023 systematic review of randomized trials (12 studies; total n = 2,134) confirmed that JAK inhibitors significantly outperform placebo on all major outcomes. For instance, JAK-treated patients had a much greater mean reduction in SALT score (~34 points from baseline) and far higher odds of achieving SALT 50, SALT 90, or SALT ≤ 20. The pooled odds ratio for SALT ≤ 20 with JAK therapy was on the order of 7 (roughly 277 per 1,000 treated achieved this outcome versus 66 per 1,000 on placebo) (12). A Bayesian network meta-analysis (15 trials; n = 3,180) also suggested that the high- est-efficacy regimens are high-dose oral agents: deuruxolitinib 12 mg and ritlecitinib 50 mg ranked highest in reducing SALT scores (based on SUCRA analysis), whereas lower doses and topical JAKs were less effective (13). Deuruxolitinib 12 mg and brepocitinib, an investigational JAK1/tyrosine kinase 2 (TYK2) inhibitor had the best rankings for achieving SALT50/75/90 endpoints followed closely by ritlecitinib 50 mg and deuruxolitinib 8 mg. In practical terms, this evidence synthesis confirms that modern oral JAK in- hibitors are currently the most potent drugs for inducing regrowth Figure 1 | Lateral view of a patient with alopecia totalis before baricitinib 4 mg once daily was commenced (Time 0) and 1, 2, and 3 months thereafter. 119 Acta Dermatovenerol APA | 2025;34:117-120 JAK Inhibitors in AA: a review article in moderate-to-severe AA (14). However, topical formulations are still in development or early trials, aiming to reduce systemic side effects while maintaining efficacy (15). Safety data so far are reassuring but warrant caution. Across trials, most treatment-emergent adverse events were mild or moderate (upper respiratory infections, nasopharyngitis, head- ache, acne, etc.) and similar to known class effects (7, 8). In the BRAVE-AA studies, patients treated with baricitinib had higher rates of acne and transient creatine kinase and lipid elevations than placebo (7). However, no drug-related deaths or thrombo- embolic events were reported through 52 weeks. A meta-analysis of nine trials (n = 1,780) found no significant increase in severe adverse events or treatment discontinuations with JAK inhibitors compared with placebo, with a pooled relative risk of 0.77 for both outcomes. However, the overall rate of treatment-related events, mostly minor infections, was modestly higher with JAK inhibitors (pooled relative risk 1.25; 95% confidence interval 1.00–1.57) (12). Long-term extension studies support a stable safety profile; for baricitinib, 104-week data showed maintained efficacy with no new safety signals noted (10). Nonetheless, known risks of JAK in- hibitors, such as serious infections, malignancy, and thrombosis, were seen in rheumatoid arthritis patients. Regulatory labels car- ry warnings about these rare events, although none were uniquely seen in the alopecia trials to date. Importantly, patient monitor- ing (labs and infection screening) is recommended in clinical use. The newer agents ritlecitinib and deuruxolitinib were approved partly based on favorable tolerability; ritlecitinib’s approval (first in adolescents ≥ 12 years; ages 12 to 75 years in trial) reflects its novel selectivity and the absence of unexpected toxicities in its trial (14). No new safety signals specifically attributable to AA pa- tients have emerged in trials, but clinicians should monitor pa- tients closely (16). Despite their promise, JAK inhibitors have limitations. A sub- stantial fraction of patients do not achieve full regrowth; for ex- ample, only about one-third to one-half reach SALT ≤ 20 even on the higher doses, and complete (SALT ≤ 10) responses remain un- common (7, 9). Crucially, AA is a relapsing disease, and regrowth typically diminishes after drug withdrawal, and so long-term or maintenance therapy may be required. Trial durations have generally been 24 to 52 weeks, and the durability of remission off-treatment is not established. Longer-term safety and optimal treatment duration are still under study (the BRAVE investigators explicitly call for multi-year data) (7). Patient heterogeneity is another challenge; trial participants were mostly adults without significant comorbidities, and so data in children < 12 years, the elderly, or those with severe systemic disease are sparse. Cost and access also affect real-world use of JAK inhibitors. In summary, high-quality evidence shows that oral JAK inhibitors can induce meaningful hair regrowth in moderate-to-severe AA (7, 19). Ongo- ing research, including head-to-head comparisons, combination strategies, and longer follow-up, will further define the place of JAK therapy in AA (17, 18, 20). Emerging combination approaches, such as JAK inhibitors administered alongside microneedling to enhance follicular penetration or combined with topical sensi- tizers (e.g., diphencyprone) have shown preliminary efficacy in small studies and may offer synergistic benefits, warranting for- mal investigation in controlled trials (21) (Table 1). Table 1 | Comparison of JAK inhibitors used for the treatment of alopecia areata and those currently in the phase of investigation, and their efficacy, safety profiles, treatment outcomes, and side effects. JAK inhibitor Target Key trials Efficacy Safety profile Treatment outcome Side effects Baricitinib JAK1/2 Phase 3 RCT 38.8% of patients receiving 4 mg of baricitinib achieved a SALT score ≤ 20 at week 36 (10) Good tolerability, see above for specific FDA approved (2022), EMA approved, high patient satisfaction URTI, nausea, headache, increased cholesterol levels, elevated liver enzymes Ritlecitinib JAK3 / TEC family kinase Phase 2b/3 23% of patients achieved a SALT score ≤ 20 at week 24 and 31% by week 48 (9) Good tolerability, nasopharyngitis, headache, URTI, and nausea FDA approved (2023), EMA approved, well suited for younger patients Nasopharyngitis, headache, acne, diarrhea, fatigue, nausea Brepocitinib TYK2 / JAK1 Phase 2 trials completed SALT score improvement in ~30% (preliminary) Well tolerated in limited studies Promising due to dual inhibition of TYK2/JAK1 Acne, upper respiratory infections, headache Deuruxolitinib JAK1/2 Phase 3 trials completed ~30% to 41% achieved SALT ≤ 20 at 24 weeks (higher dose) Well tolerated, dose-dependent adverse effects Promising alternative to baricitinib with similar response rate Headache, acne, nasopharyngitis, elevated CPK, liver enzymes ATI-502 (topical) JAK1/3 Phase 2 trials completed Modest regrowth in ~28% (based on investigator global assessment) Excellent topical safety, minimal systemic absorption Less effective than oral JAK; low risk makes it suitable for limited patches Mild irritation at application site ATI-1777 (topical) JAK1/3 Phase 2a trials initiated Early data not yet public Designed for minimal systemic exposure Still investigational; could suit patients with localized AA Local skin effects only SHR0302 Selective JAK1 Phase 2 trial completed Moderate efficacy; ~25% to 30% regrowth in responders Mild; JAK1 selectivity lowers systemic risk Considered safe and moderately effective in Asian populations Headache, mild GI symptoms, increased cholesterol levels, thrombocytopenia, raised liver enzymes Delgocitinib JAK1/2/3 and TYK2 Topically tested for dermatological diseases and AA early phase Limited data in AA; effective in eczema Safe topical use; no serious systemic events Possibly helpful in scalp application; awaiting AA-specific results Application site irritation AA = alopecia areata, CPK = creatine phosphokinase, EMA = European Medical Agency, FDA = food and drug administration, GI = gastrointestinal, JAK = Janus kinase, JAK = Janus kinase inhibitors, RCT = randomly controlled trial, SALT = Severity of Alopecia Tool, TEC = tyrosine kinase, URTI = upper respiratory tract infection, UTI = urinary tract infection, TYK2 = tyrosine kinase 2. 120 Acta Dermatovenerol APA | 2025;34:117-120 J. 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