Upadacitinib for Alopecia: Current Evidence and Clinical Insights Open Access

Alopecia areata (AA) is a hair loss disorder that impacts patients’ physical appearance, psychosocial well-being, and quality of life. The lifetime risk of developing AA approaches 2%, making it the second most common form of hair loss after androgenetic alopecia [1]. Between 1990 and 2009 in Olmsted County, Minnesota, the incidence of AA was 20.2 per 100,000 person-years, and similar studies have reported increasing prevalence in recent decades [2]. AA typically manifests as patchy, non-scarring hair loss but can progress to more extensive variants, such as alopecia totalis (AT) or alopecia universalis, in which the entire scalp or body hair is lost, respectively. These more severe subtypes often correlate with higher rates of treatment resistance, relapse, and psychological distress [1, 2].

The pathogenesis of AA is primarily driven by autoimmune mechanisms. It is suggested that a dysregulated T-lymphocyte response targets hair follicle-associated antigens, triggering inflammatory cascades that result in hair follicle collapse and arrest of the hair growth cycle [3]. This process is frequently associated with other autoimmune diseases, including atopic dermatitis, thyroid dysfunction, and vitiligo [4]. Conventional treatment approaches, including topical corticosteroids, intralesional steroid injections, topical immunotherapy (e.g., diphenylcyclopropenone), systemic agents (e.g., methotrexate, cyclosporine), and biologics demonstrate variable efficacy and often fail to achieve long-lasting remission [5, 6]. Relapse rates following withdrawal of these medications can exceed 30–50%, highlighting the significant unmet need for more durable treatment options [7].

Over the last decade, increasing attention has focused on the Janus kinase (JAK) signal transducer and activator of transcription pathway, which orchestrates a wide range of immune responses. Dysregulation of this pathway has been implicated in multiple inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriasis, and atopic dermatitis [8, 9]. Notably, preclinical and clinical data have demonstrated that JAK inhibition can reverse the autoimmune targeting of hair follicles in AA, promoting hair regrowth even in long-standing or severe disease [10]. Use of relatively non-selective JAK inhibitors, such as tofacitinib and ruxolitinib, has advanced our understanding of JAK receptor subtypes, enabling the development of more targeted agents like upadacitinib, a selective JAK1 inhibitor [11].

Upadacitinib has garnered approval for treating rheumatoid arthritis and atopic dermatitis, with emerging evidence showing potential efficacy in AA [12]. Early reports suggest that selective JAK1 inhibition may confer immunomodulatory benefits while minimizing off-target effects. In addition to scalp hair regrowth, improvements in comorbid conditions (e.g., atopic dermatitis, inflammatory bowel disease) have also been reported, underscoring the broader anti-inflammatory impact of this medication [13]. Baricitinib was the first FDA-approved JAK inhibitor for AA, followed by ritlecitinib, which targets both JAK and TEC kinases, and deuruxolitinib, which is not yet available [14, 15]. Other JAK inhibitors, including tofacitinib, ruxolitinib, and upadacitinib, are currently used off-label. Despite this, much of the evidence for upadacitinib’s use in AA stems from case reports and small series, necessitating larger studies to establish definitive safety and efficacy profiles.

Given the rising global burden of AA, and in particular the emotional and psychosocial stress experienced by patients, 60% of whom report moderate-to-severe negative impact on daily life [7], innovative therapies such as upadacitinib demand rigorous investigation. A broader synthesis of current clinical data can help physicians better understand the potential role of selective JAK1 inhibition in this setting. Therefore, we performed a scoping review to collate published reports on upadacitinib use for AA, with the aim of delineating patient characteristics, regimens, clinical responses, adverse events, and quality-of-life impacts. By consolidating these findings, we hope to define the emerging therapeutic profile of upadacitinib in alopecia; identify evidence gaps; and guide future research on dosing strategies, long-term safety, and combination approaches.

A scoping review was performed to synthesize current evidence on upadacitinib treatment for alopecia. A comprehensive search was performed in August 2024 across PubMed, Embase, CINAHL, MEDLINE, Web of Science, and CENTRAL, using the terms “upadacitinib” AND “alopecia,” with no restrictions on language or publication date. Reference lists of relevant articles were screened for additional studies.

As detailed in the PRISMA flow diagram (shown in Fig. 1), 221 studies were identified from database searches: PubMed (n = 44), Embase (n = 50), CINAHL (n = 55), MEDLINE (n = 40), Web of Science (n = 27), and CENTRAL (n = 5). After removing 50 duplicates, 171 studies underwent title and abstract screening, excluding 121 that were irrelevant. Fifty studies were sought for full-text retrieval, with 1 unavailable. Of the 49 assessed, 23 were excluded: 2 for non-English language, 14 for irrelevant outcomes, and 9 for unsuitable designs. Ultimately, 24 studies met the inclusion criteria.

Peer-reviewed publications (original research, case reports, case series, or retrospective/prospective analyses) were included, describing upadacitinib use for any hair loss condition and excluded abstracts, non-human, and in vitro studies. Two independent reviewers conducted screening and full-text reviews (TS and ST), resolving discrepancies by consensus. Extracted data included study characteristics, patient demographics, comorbidities, hair loss type, upadacitinib regimens (dose, route, duration), concomitant treatments, clinical and laboratory outcomes, quality-of-life measures, adverse events, and follow-up.

Statistical analyses were descriptive, summarizing patient demographics, alopecia subtypes, treatment regimens, and clinical outcomes using means, medians, ranges, and proportions. Matching data were aggregated where possible, with continuous variables, including Severity of Alopecia Tool (SALT) and Dermatology Life Quality Index (DLQI) scores averaged to highlight central tendencies and ranges reported for variability. Proportions were calculated for categorical outcomes, enabling a consolidated interpretation of upadacitinib’s efficacy and safety across diverse populations and alopecia subtypes.

A total of 24 publications were included, spanning 2022 (n = 4), 2023 (n = 8), and 2024 (n = 12), and published in 21 journals. Geographically, most studies were conducted in Italy (n = 8, 33.3%), followed by China and Canada (n = 3 each, 12.5%) (shown in Table 1).

A total of 64 patients with AA were described, with a mean age of 27.0 years (range 9–67), comprising 29 males (45.3%) and 35 females (54.7%). Ethnicity was unspecified in 61 patients (95.3%), with 3 (4.7%) reported as Caucasian/White. Disease duration before treatment ranged from 2 months to 35.0 years. Among these patients, the most common AA subtypes included universalis (n = 28), ophiasis (n = 15), alopecia totalis (n = 8), unspecified (n = 6), patchy (n = 3), multifocal (n = 3), and diffuse (n = 1). Comorbidities were predominantly atopic or autoimmune, with atopic dermatitis (59.4%) being the most common. Less frequently reported conditions included Hashimoto’s thyroiditis (6.3%), asthma (4.7%) and Crohn’s disease (3.1%).

Prior treatments varied. Among treated patients, 43 (67.2%) were treated with systemic corticosteroids or cyclosporine, 25 (39.1%) had topical treatments (corticosteroids, minoxidil, diphenylcyclopropenone immunotherapy), and 17 (26.5%) had biologic therapies, generally with partial or minimal benefit. Upadacitinib doses were 15 mg in 34 patients (53.1%) and 30 mg in 30 patients (46.9%). Mean duration of treatment was 6.6 months, with a range of 1–12 months across all patients. Dose adjustments (e.g., from 15 mg to 30 mg/day) were individualized based on clinical response and tolerability. Most reported no concomitant treatments (n = 58, 90.6%), with concomitant treatments of oral minoxidil, intralesional triamcinolone, topical corticosteroids, gabapentin, ustekinumab, NB-UVB, and topical calcineurin inhibitors rarely reported (each n = 1, 1.6%).

Across 19 studies reporting baseline SALT scores (n = 56), mean SALT at baseline was 91.3 (range 13–100). By the final assessment (n = 37), mean SALT had decreased to 5.3 (range 0–74.4). Among 8 non-SALT-based reports, 9 described complete hair regrowth of the scalp, eyebrows, and eyelashes, 6 noted partial improvement, and 1 indicated worsening alopecia.

Additional benefits reported across case studies included improvements in atopic dermatitis, psoriasis, arthritis, and inflammatory bowel disease. Qualitative assessments showed remission or significant improvement in psoriatic arthritis (n = 1). Improvement was often seen within 1 month (n = 51, 79.7%), with others improving over 2–5 months (n = 12, 18.8%). DLQI improvement was noted in 6 patients, with mean DLQI reported in 4 patients decreasing from 20.3 to 6.0 (shown Table 2).

Of the 61 specified cases, the primary reason for prescribing upadacitinib was the presence of comorbidities (n = 35, 57.4%), followed by drug availability/cost constraints (n = 17, 27.9%), refractory or other reasons (n = 8, 13.1%), and failure of a different JAK inhibitor (n = 1, 1.6%). Thus, most patients received upadacitinib to address multiple simultaneous inflammatory conditions, with access/affordability considerations being the second most common driver.

Overall follow-up periods (n = 64) ranged from 2 to 17 months, with a mean of 6.8 months. Among the 12 patients on upadacitinib maintenance therapy, the mean daily dose was 17.1 mg (median 15 mg; range 15–30 mg). Most patients (12/14) received 15 mg/day, while 2/14 were on 30 mg/day. Of the reports specifying relapse data, 4 patients (all of whom discontinued or reduced their medication) relapsed within 1–6 months; notably, regrowth resumed with reintroduction of upadacitinib (shown in Table 3).

In general, upadacitinib was well tolerated. Mild adverse events included transient creatine phosphokinase elevations (n = 6), acneiform eruptions (n = 6), mild upper respiratory infections (n = 1), elevated leukocyte count (n = 2), transient leukopenia (n = 1), and occasional transient liver enzyme or lipase/amylase elevations (n = 3). No serious or persistent adverse events were reported, and none necessitated treatment discontinuation.

Upadacitinib has demonstrated considerable promise in the treatment of AA and its severe variants, with growing evidence supporting its clinical efficacy across diverse patient populations, including those who have failed conventional treatments. High rates of significant or complete hair regrowth were observed, often within 1–4 months of initiating therapy. Notably, some patients with coexisting autoimmune disorders such as atopic dermatitis, inflammatory bowel disease, or psoriasis experienced concurrent improvements, suggesting that selective JAK1 inhibition may confer broader immunomodulatory benefits in these overlapping conditions.

The drug’s generally favorable safety profile bolsters its potential appeal for long-term use. Mild and transient adverse events were acneiform eruptions, brief leukopenia, or reversible elevations in liver enzymes or creatine phosphokinase. Although no major or persistent adverse events occurred in the studies reviewed, larger trials and real-world registries remain essential to monitor for rare but significant complications, including thromboembolic events, severe infections, or malignancies, that have been documented with other JAK inhibitors in different disease settings. The variability in dosing practices, ranging from 15 mg/day to 45 mg/day, also highlights the need to clarify optimal treatment strategies and maintenance regimens. Additionally, the risk of disease recurrence upon tapering or discontinuation needs further evidence-based protocols for upadacitinib maintenance therapy.

Despite mainly single patient reports and small case series, the consistency of beneficial outcomes across diverse alopecia subtypes reinforces the view that JAK1 inhibitors may represent a unifying therapeutic approach in autoimmune-driven hair loss. Combining upadacitinib with adjunctive treatments such as topical or oral minoxidil, corticosteroids, or phototherapy may further bolster efficacy, but data on combination regimens are sparse. Given the chronic and often relapsing-remitting course of AA, especially in its more extensive forms, it is also crucial to evaluate patient-reported outcomes, including DLQI, and the impact on mental health. Anecdotal evidence from these case series indicates that robust hair regrowth often leads to marked improvements in mood and self-esteem, aligning with the extensive literature on the psychosocial burden of hair loss.

Randomized controlled trials are essential to determine upadacitinib’s position in the therapeutic landscape for AA. It is important to employ standardized and validated outcome measures for objective assessment of hair regrowth and quality of life, including SALT scoring, Skindex-16, or other relevant tools tailored for AA. These measures would facilitate cross-study comparisons and meta-analyses. It is important for randomized controlled trials to address the relative efficacy of various dosage regimens, the role of induction versus maintenance therapy, and the incidence and severity of adverse events over longer follow-up periods.

Two ongoing studies are evaluating upadacitinib for AA. A US-based Phase 3, randomized, placebo-controlled study (M23-716), initiated on October 11, 2023, is recruiting 1,500 participants aged 12–63 years with severe AA (SALT score ≥50) and disease duration under 8 years. The trial is expected to conclude in January 2028. A real-world observational study in China (NCT06573593), started on July 29, 2024, is enrolling 150 AA patients aged 2–80 years who have been treated with JAK inhibitors, including upadacitinib, for over 3 months. This study aimed to compare the treatment outcomes of AA patients treated with tofacitinib, baricitinib, ritlecitinib, abrocitinib, upadacitinib, and itdancitinib, focusing on clinical efficacy (e.g., SALT score improvements) and safety profiles (e.g., adverse events) [39, 40]. Concurrent mechanistic research, incorporating transcriptomic and immunologic studies, could help identify biomarkers of response, revealing subsets of patients most likely to benefit from JAK1-specific inhibition while sparing those who might be better served by alternative modalities.

Additional limitations of the current evidence base warrant careful consideration. The majority of data stems from case reports and small observational studies, which are prone to publication bias and often lack standardized reporting of key variables such as baseline disease severity, laboratory monitoring protocols, and comorbidities. Heterogeneity in alopecia subtypes, disease duration, and prior treatments further complicates the synthesis of findings and underscores the need for more rigorous study designs. Pediatric and adolescent patients are also underrepresented in the existing literature, leaving physicians with limited guidance for younger populations who may experience a considerable psychosocial toll from hair loss. Moreover, extended follow-up beyond 6–12 months is sparse, making it difficult to ascertain the durability of regrowth and the long-term risk-benefit profile of upadacitinib. Cost considerations remain another factor; although JAK1 inhibitors generally show good cost-effectiveness in some inflammatory diseases, formal pharmacoeconomic evaluations specific to AA are lacking.

In sum, while the collective data suggest upadacitinib holds promise as a therapy for AA, confirmation of its safety, efficacy, and best-use practices requires more robust clinical investigations. Advancing our understanding of selective JAK inhibition and conducting rigorously designed studies may refine upadacitinib’s role in managing AA and enhancing patient quality of life.

The authors have no conflicts of interest to declare. Dr. Shari Lipner has received research funding from BelleTorus Corporation and Moberg Pharmaceuticals, unrelated to this study. Dr. Carolyn Goh is a speaker for Pfizer, Inc., and has received consulting fees from Sagimet Biosciences.

This study was not supported by any sponsor or funder.

T.S. conducted literature review, data collection, preliminary statistical analysis, and manuscript drafting. S.T. contributed to the literature search and provided guidance and feedback. D.B. conducted the final data analysis. C.G. provided valuable edits and feedback given her background in hair research. S.L. supervised the project, critically reviewed the manuscript, and approved the final version.

All data supporting this review are derived from previously published studies, as cited in the reference list.