Ritlecitinib for the Management of Alopecia Areata: A Narrative Review of Real-World Evidence and Selected Post Hoc Analyses

Abstract

Introduction: Alopecia areata (AA) is a chronic immune-mediated disorder characterized by non-scarring hair loss and a significant psychosocial burden. Ritlecitinib, a selective Janus kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, has recently emerged as a targeted systemic therapy for moderate-to-severe AA. While randomized clinical trials have demonstrated its efficacy, real-world evidence remains limited and heterogeneous. Methods: A structured narrative review was conducted to summarize current evidence on ritlecitinib in AA, with a focus on real-world outcomes. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to March 2026 using predefined keywords. Eligible studies included real-world observational studies, case series, and post hoc analyses of randomized controlled trials reporting clinical outcomes. Two independent reviewers performed study selection. Results: A total of 14 studies were included. Clinical trial analyses suggested sustained efficacy over time, with progressive improvement in Severity of Alopecia Tool (SALT) scores up to 24 months. Real-world studies reported clinically meaningful hair regrowth across diverse populations, including severe, pediatric, and treatment-experienced patients. Response rates increased over time, with a proportion of patients achieving SALT ≤ 20 or ≥80% improvement. Lower baseline severity and shorter disease duration were reported in several studies as potential factors associated with a better response. Safety profiles were favorable, with predominantly mild adverse events. Discussion: Ritlecitinib shows consistent effectiveness and acceptable safety in both clinical trials and real-world settings. Treatment response appears progressive and heterogeneous, supporting the importance of early intervention and adequate treatment duration. Further large-scale and long-term real-world studies are needed to better define predictors of response and optimize patient selection.

1. Introduction

Alopecia areata (AA) is a chronic immune-mediated disorder characterized by non-scarring hair loss that can involve the scalp, eyebrows, eyelashes, and other body areas [1]. The clinical presentation is highly heterogeneous, ranging from localized patchy hair loss to more extensive phenotypes such as alopecia totalis and alopecia universalis, which involve complete loss of scalp or body hair [1]. Although AA is not associated with permanent follicular destruction, the unpredictable disease course, frequent relapses, and potential progression to extensive forms contribute to a substantial psychological and psychosocial burden [2]. Patients with moderate-to-severe AA often experience significant impairment in quality of life, including emotional distress, anxiety, depression, and social withdrawal, highlighting the need for effective long-term therapeutic strategies [3].

The pathogenesis of AA is primarily driven by an autoimmune process targeting the hair follicle [4,5,6]. Increasing evidence indicates that the collapse of hair follicle immune privilege plays a central role in disease initiation and progression [4,5,6]. Cytotoxic CD8⁺ NKG2D⁺ T lymphocytes infiltrate the hair follicle bulb and release pro-inflammatory cytokines, including interferon-γ and interleukin-15, which amplify the inflammatory cascade [4,5,6]. These cytokines activate intracellular signaling pathways mediated by Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, ultimately leading to sustained immune activation and disruption of normal hair follicle cycling [4,5,6]. This growing understanding of the molecular mechanisms underlying AA has provided the biological rationale for the development of targeted therapies aimed at modulating the JAK–STAT signaling pathway [7].

Over the past decade, the therapeutic landscape of AA has undergone a profound transformation with the introduction of JAK inhibitors [8,9]. Traditional treatments, including topical or intralesional corticosteroids, systemic immunosuppressants, and topical immunotherapy, have historically shown variable and often limited efficacy, particularly in patients with extensive or refractory disease [8,9]. In contrast, JAK inhibitors directly target key signaling pathways involved in AA pathogenesis and have demonstrated clinically meaningful efficacy in promoting hair regrowth [8,9]. Among these agents, baricitinib and ritlecitinib have recently emerged as effective systemic therapies supported by robust clinical trial data [10].

Ritlecitinib is an oral small-molecule inhibitor that selectively targets JAK3 and members of the TEC kinase family [11]. By modulating signaling pathways involved in lymphocyte activation and cytokine-mediated immune responses, ritlecitinib interferes with critical mechanisms driving autoimmune hair follicle attack [11]. This dual inhibition profile may contribute to its immunomodulatory effects while potentially minimizing broader JAK-related off-target activity [11]. The efficacy and safety of ritlecitinib in AA have been primarily demonstrated in the ALLEGRO clinical trial program, which included phase 2b/3 randomized controlled trials and long-term extension studies evaluating its use in adolescents and adults with moderate-to-severe disease [12]. These studies reported significant improvements in scalp hair regrowth and clinically meaningful reductions in disease severity, as measured by the Severity of Alopecia Tool (SALT) score—a standardized instrument used to estimate the percentage of scalp hair loss on a scale from 0 to 100, with higher scores indicating greater disease severity—leading to regulatory approval of ritlecitinib for the treatment of AA in several countries [12]. However, while randomized clinical trials provide essential evidence regarding drug efficacy and safety, their findings may not fully reflect treatment outcomes in routine clinical practice [13]. As a result, real-world evidence has become increasingly important for understanding how newly approved therapies perform outside the controlled environment of clinical trials. Since the recent introduction of ritlecitinib into clinical practice, an increasing number of observational studies and real-world reports have been published, providing valuable insights into its effectiveness, response kinetics, and safety profile in diverse patient populations [14,15]. These emerging data contribute to a more comprehensive understanding of ritlecitinib in the management of AA, complementing the evidence derived from randomized clinical trials. Nevertheless, the currently available literature remains relatively limited and heterogeneous, particularly regarding real-world clinical outcomes, patient selection, and long-term effectiveness.

In this context, the present structured narrative review aims to summarize and critically appraise the currently available evidence on ritlecitinib in alopecia areata. Particular emphasis is placed on real-world clinical outcomes, while selected post hoc analyses from randomized clinical trials are also discussed to provide a comprehensive overview of the efficacy, safety, and potential predictors of response associated with ritlecitinib therapy in patients with AA.

2. Materials and Methods

This study was conducted as a structured narrative review aimed at summarizing and critically appraising the available evidence on the use of ritlecitinib in patients with AA, with a specific focus on real-world clinical outcomes and selected post hoc analyses of randomized clinical trials (RCTs). A comprehensive literature search was performed in PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library, including all articles published up to March 2026. The search strategy combined Medical Subject Headings (MeSH) and free-text terms. The following keywords were used in different combinations: “ritlecitinib”, “alopecia areata”, “AA”, “JAK inhibitors”, “real-world”, “real-life”, “clinical practice”, “observational study”, “case series”, and “post hoc analysis”. Boolean operators (AND/OR) were applied to optimize sensitivity and specificity of the search strategy. Titles and abstracts of retrieved records were screened for relevance, followed by full-text evaluation of potentially eligible studies. To reduce selection bias, two independent authors (G.L. and L.P.) performed the screening process and assessed study eligibility. Discrepancies were resolved through discussion and consensus. Studies were considered eligible if they met the following inclusion criteria: (i) clinical studies evaluating ritlecitinib in patients with alopecia areata; (ii) real-world observational studies, including retrospective and prospective cohorts, multicenter studies, and case series; (iii) post hoc analyses of RCTs reporting clinically relevant outcomes; and (iv) studies published in English. Both adult and pediatric populations were considered eligible. Exclusion criteria included: (i) preclinical studies; (ii) narrative reviews, editorials, or conference abstracts without full-text availability; (iii) studies not reporting clinical outcomes; and (iv) duplicate reports of the same patient cohort. Given the relatively recent introduction of ritlecitinib in clinical practice, both real-world evidence and selected post hoc analyses of clinical trials were included to provide a comprehensive overview of treatment effectiveness and safety. Reference lists of all included articles were manually screened to identify additional relevant studies not captured through the initial search. The last literature search was performed on 31 March 2026. Through this search strategy, a total of 278 potentially relevant records were initially identified. After removal of duplicates, 176 records remained for title and abstract screening. Of these, 139 were excluded because they did not meet the predefined eligibility criteria, mainly due to lack of relevance to alopecia areata, absence of ritlecitinib-specific clinical outcomes, review/editorial article type, preclinical or pharmacological focus, conference-only publication, non-English language, or duplicate cohort reporting. Thirty-seven full-text articles were assessed for eligibility, and 23 were excluded following full-text review. Ultimately, 14 studies met the predefined inclusion criteria and were included in the qualitative synthesis. Due to the narrative design of this review and the heterogeneity of study designs, patient populations, outcome measures, and follow-up durations, no formal risk-of-bias assessment or quantitative meta-analysis was performed. The objective of this review was to provide a structured qualitative synthesis of the currently available evidence. This study is based exclusively on previously published data and did not involve new data collection or human participants.

3. Results

A total of 14 studies were included in this narrative review, comprising clinical trials/post hoc analyses and real-world observational studies (

Table 1. Summary of post hoc analyses of randomized clinical trials and real-world studies evaluating the effectiveness and safety of ritlecitinib in patients with alopecia areata. Further details on follow-up duration, timing of outcome assessment, previous JAK inhibitor exposure, and concomitant therapies are reported in the main text for individual studies, when available.

Study	Design	Population	Key Efficacy Outcomes	Safety	Key Notes
Fu et al. [16]	Post hoc analysis (ALLEGRO)	n = 522; ≥50% scalp hair loss	At W24: ILCS ↑ SALT ≤ 20 (OR 2.12); systemic IS ↓ response (OR 0.50); topical therapy ↑ SALT ≤ 10; no associations at W48	Not specifically assessed	Prior treatments do not impact long-term response
Reguiai et al. [17]	Long-term analysis (ALLEGRO + LTE)	n = 191; severe AA (71.2% SALT > 90)	Progressive shift to SALT 0–10 and 10–20 up to 24 months; efficacy also in AT/AU and adolescents	Not reported	Sustained long-term efficacy
Valtellini et al. [18]	Multicenter retrospective	n = 12; severe AA	SALT ↓ 91→66 (W12) →46 (W24); 50% SALT ≤ 20; early (41.7%) vs. gradual responders	Mild AEs (acne 16.7%)	Heterogeneous response kinetics
Zhang et al. [19]	Multicenter retrospective	n = 100; mixed severity; 36% prior JAKi	SALT50 69%; SALT75 56%; SALT ≤ 20 43.9% (severe AA); lower baseline SALT predicts response	Mild AEs; discontinuation 21%	Female sex and eyebrow/eyelash involvement ↓ response
Sebastian et al. [20]	Retrospective cohort	n = 139; severe AA	SALT ≤ 20: 28.4% (W16–20) → 47.3% (9 months); mean SALT reduction 45.4	Mild AEs (26%)	Better outcomes with shorter disease duration
Dai et al. [21]	Single-center retrospective	n = 29; 37.9% prior JAKi	SALT ≤ 20: 55.2% (W12) → 71.4% (W24); ≥80% improvement in 31% (W12)	Mild AEs; no discontinuations	Better trend in JAKi-naïve patients
Okazaki et al. [22]	Single-center retrospective	n = 22; naïve vs. baricitinib-experienced	SALT75: 77.8% naïve vs. 7.7% experienced; SALT90: 55.6% vs. 7.7%	No AEs	Markedly reduced efficacy after prior JAKi
Sheng et al. [23]	Single-center retrospective	n = 35; severe AA	SALT ≤ 20: 11.4% (W12) → 40% (W24); SALT ≤ 10: 22.9% (W24) + complete regrowth 11.4% (W24)	Mild AEs (folliculitis 34.2%)	Worse response with higher severity and longer duration
Xu et al. [24]	Single-center retrospective	n = 25; moderate AA	SALT ≤ 20: 40% (W8) → 76% (W16); SALT75: 36% (W16)	Few AEs (elevated liver enzymes, dyslipidaemia)	Early response; high IgE predicts non-response
Franzese et al. [25]	Single-center retrospective	n = 11; adolescents	SALT ≤ 20: 45.5%; SALT ≤ 10: 27.3% (W24)	Mild AEs	Good efficacy without concomitant therapy
Wang et al. [26]	Retrospective study	n = 18; children < 12	SALT ≤ 20: 55.6%; SALT50: 83.3%; SALT75: 66.7%	Mild AEs	Better response with lower severity and shorter disease duration
Huang et al. [27]	Case series	n = 10; pediatric	SALT ≤ 20: 100% (W24 evaluable); ≥80% improvement in 71%; 50% full regrowth	Mild AEs	Strong efficacy in selected pediatric cases
Huang et al. [28]	Retrospective cohort	n = 18; JAKi-refractory	SALT ≤ 20: 44.4%; SALT ≤ 10: 27.8%; ≥80% improvement 22.2%	Mild–moderate AEs	Effective switch strategy in subset
Foggia et al. [29]	Comparative real-world	n = 56 (19 ritlecitinib)	SALT ↓ 87.85 → 41.98 (W24); no differences vs. baricitinib/upadacitinib	No serious AEs	Comparable efficacy across JAK inhibitors

Abbreviations: AA, alopecia areata; AE/AEs, adverse event(s); AT/AU, alopecia totalis/alopecia universalis; IgE, immunoglobulin E; ILCS, intralesional corticosteroids; IS, immunosuppressants; JAKi, Janus kinase inhibitor; LTE, long-term extension; OR, odds ratio; SALT, Severity of Alopecia Tool; SALT50/75/90, ≥50%/≥75%/≥90% improvement in SALT score from baseline; W, week. Symbols: ↑, increased likelihood or improvement; ↓, decreased likelihood or reduction.

). Overall, the available evidence on ritlecitinib in AA is still emerging, with a predominance of real-world data and a limited number of analyses derived from randomized clinical trials (RCTs).

3.1. Clinical Trials and Post Hoc Analyses

Evidence from RCTs is mainly derived from post hoc analyses of the ALLEGRO phase 2b/3 program, which explored factors potentially influencing treatment response. A post hoc analysis of the phase 2b/3 ALLEGRO trial evaluated the impact of prior AA treatments on clinical response to ritlecitinib up to W48 in a cohort of 522 patients aged ≥12 years with ≥50% scalp hair loss [16]. Overall, 69.0% (360/522) of patients had received at least one prior AA therapy, most commonly topical treatments (51.0%), followed by systemic immunosuppressants (33.7%), intralesional corticosteroids (ILCS; 25.7%), and topical immunotherapy (16.7%) [16]. At W24, prior treatment exposure showed a differential association with treatment response. Specifically, prior use of ILCS was positively associated with achieving a SALT score ≤ 20 (OR 2.12; 95% CI 1.23–3.65; p < 0.05), whereas prior exposure to systemic immunosuppressants was negatively associated with this endpoint (OR 0.50; 95% CI 0.28–0.88; p < 0.05) [16]. No significant associations were observed for prior use of topical therapies or topical immunotherapy. A similar pattern was observed for the more stringent endpoint of SALT ≤ 10 at W24, where prior topical therapy was associated with improved response (OR 2.13; 95% CI 1.17–3.95; p < 0.05), while other treatment categories showed no significant impact [16]. However, these associations were not maintained over time. By W48, no significant relationship was observed between prior exposure to any AA therapy and treatment response, both for SALT ≤ 20 and SALT ≤ 10 endpoints (all p > 0.05) [16]. Notably, prior exposure to any AA treatment overall was not associated with treatment response at either W24 or W48 [16].

Long-term efficacy trajectories of ritlecitinib have been further explored through analyses of SALT score distribution over time [17]. In a longitudinal analysis including 191 patients enrolled in the ALLEGRO-2b/3 and long-term extension (ALLEGRO-LT) studies, all participants had ≥50% scalp hair loss at baseline, with 71.2% presenting with severe disease (SALT > 90) [17]. Over a 24-month follow-up, a progressive shift toward lower SALT score categories was observed. The proportion of patients with severe disease (SALT > 90–100) decreased substantially from baseline to Month 24, from 71.2% at baseline to 17/120 among evaluable patients at Month 24 [17]. Conversely, clinically meaningful hair regrowth increased over time, with a growing proportion of patients achieving SALT 0–10 and SALT 10–20 categories. At Month 12, 56/164 and 18/164 patients reached SALT 0–10 and >10–20, respectively, increasing to 61/120 and 12/120 at Month 24 [17]. Consistent improvements were also observed in patients with more severe baseline phenotypes. Among those with alopecia totalis or universalis (AT/AU), 25/47 patients achieved SALT 0–10 and 3/47 achieved SALT 10–20 at Month 24. Similarly, in the adolescent subgroup, 11/14 patients reached SALT 0–10 at Month 24 [17].

3.2. Real-World Evidence

3.2.1. Multicenter Real-World Studies

Real-world evidence on ritlecitinib in AA is still limited, but the currently available multicenter studies suggest clinically meaningful effectiveness, with progressive improvements in scalp hair regrowth, eyebrow/eyelash involvement, and selected patient-reported outcomes. In a 24-week multicenter retrospective study conducted across three Italian tertiary centers, Valtellini et al. evaluated the effectiveness and safety of ritlecitinib 50 mg once daily in 12 patients aged ≥12 years with severe AA [18]. The cohort was predominantly adolescent (median age 16 years), with a high disease burden at baseline (mean SALT 91.0 ± 16.6), and a high prevalence of extensive phenotypes, including alopecia universalis (58.3%) and alopecia totalis (16.7%) [18]. A progressive improvement in scalp involvement was observed over time, with mean SALT decreasing from 91.0 at baseline to 66.0 at W12 and 46.0 at W24 (p < 0.001), and 50.0% of patients achieving SALT ≤ 20 at W24. Notably, heterogeneous response kinetics were described, with 41.7% of patients classified as early responders (≥30% SALT improvement by W12) and 25.0% as gradual responders [18]. Improvement was also observed in extra-scalp involvement, with a progressive reduction in eyebrow and eyelash severity scores over time. Ritlecitinib was well tolerated, with only mild adverse events (AEs) reported, including acne in 16.7% of patients [18].

Larger real-world evidence is provided by a multicenter retrospective study conducted across three centers in China, including 100 patients with AA treated with ritlecitinib for at least 3 months [19]. The cohort had a mean age of 26.1 ± 11.2 years and included a wide spectrum of disease phenotypes, with 44.0% presenting with alopecia totalis or universalis and a mean baseline SALT score of 58.3 ± 33.7. Notably, the majority of patients (84.0%) had previously received systemic treatments, including prior exposure to JAK inhibitors in 36.0%, reflecting a heavily pre-treated population [19]. Overall, ritlecitinib demonstrated substantial clinical effectiveness, with 69.0% and 56.0% of patients achieving SALT50 and SALT75 responses, respectively. Among patients with severe disease (baseline SALT ≥ 50), 43.9% achieved SALT ≤ 20 [19]. Treatment response was influenced by baseline disease characteristics, with higher response rates observed in patients with milder disease forms compared with those with extensive involvement, such as alopecia totalis or universalis (p < 0.05) [19]. In line with this, logistic regression analysis identified lower baseline SALT score as a predictor of improved response (OR 0.959 per unit reduction; p = 0.022). Additional predictors of treatment response emerged from this analysis. Female sex was associated with a lower likelihood of achieving SALT ≤ 20 (OR 0.233; p = 0.012), while the absence of eyebrow or eyelash involvement significantly increased the probability of response in patients with severe disease (OR 3.659; p = 0.024) [19]. Conversely, age and disease duration were not significantly associated with treatment outcomes. The safety profile was consistent with previous reports, with mostly mild AEs, including folliculitis (12.0%), acne (6.0%), and headache or dizziness (3.0%). Treatment discontinuation occurred in 21% of patients, mainly due to lack of efficacy, remission, or non-medical reasons, with only a minority of relapses observed during follow-up [19].

3.2.2. Single-Center Real-World Studies

In a large retrospective real-world study from a UK tertiary center, Sebastian et al. reported outcomes in 139 consecutive patients with severe AA treated with ritlecitinib 50 mg daily [20]. The cohort had a mean age of 38.2 years, a mean disease duration of 11.5 years, and a mean baseline SALT score of 70.7; notably, 37.0% of patients had alopecia totalis or universalis and 25.0% had previous exposure to JAK inhibitors, indicating a clinically challenging population [20]. At W16–20, SALT data were available for 74 patients, of whom 21 (28.4%) achieved SALT < 20. At 9 months, among 55 evaluable patients, 26 (47.3%) achieved SALT ≤ 20, with a mean SALT reduction of 45.4 points, supporting a progressive increase in clinical benefit over time [20]. Extra-scalp involvement also improved: among patients with paired assessments at baseline and W16–20, eyebrow improvement was observed in 33/69 (47.8%) and eyelash improvement in 31/68 (45.6%), with normalization in a subset of responders. By contrast, quality-of-life changes appeared less pronounced, with median DLQI showing no relevant early improvement at W16–20 and only a modest reduction by 9 months [20]. Safety findings were overall reassuring: AEs were reported in 26.0% of patients and were mostly mild, including respiratory tract infections, gastrointestinal symptoms, acne, and headache, while laboratory abnormalities were observed in 15.0% without leading to treatment discontinuation [20]. Interestingly, shorter disease duration appeared to favor response, as SALT ≤ 20 at W16–20 was achieved by 43% of patients with disease duration < 4 years versus 20% of those with longer-standing disease [20].

In a further single-center real-world study from China, Dai et al. evaluated the effectiveness and safety of ritlecitinib in 29 patients with AA and baseline SALT ≥ 20, including 11 patients (37.9%) previously exposed to JAK inhibitors [21]. The cohort had a mean age of 28.3 years, a mean disease duration of 5.45 years, and a high prevalence of severe phenotypes, with 65.5% showing eyebrow/eyelash involvement and 48.3% presenting with alopecia universalis [21]. Prior JAK inhibitor-exposed patients had significantly longer disease duration than JAK inhibitor-naïve patients (7.0 vs. 4.5 years; p = 0.02) and more frequent eyebrow/eyelash involvement (90.9% vs. 50.0%; p = 0.03). Overall, ritlecitinib showed clinically meaningful effectiveness [21]. After W12, 55.2% of patients achieved SALT ≤ 20 and 31.0% achieved ≥80% improvement in SALT score. Among the 14 patients who remained on treatment at W24, the median SALT further decreased to 19.14, and 71.4% achieved both SALT ≤ 20 and ≥80% SALT improvement [21]. Outcomes numerically favored JAK inhibitor-naïve patients at both time points, although these differences did not reach statistical significance. Similarly, eyebrow/eyelash improvement was observed in 68.4% of evaluable patients at W12 and in 81.8% at W24 [21]. Treatment was generally well tolerated. AEs were mild and included folliculitis, upper respiratory infection, and urticaria, with no serious AEs or treatment discontinuations reported [21].

In a retrospective single-center study from Japan, Okazaki et al. specifically compared 24-week outcomes of ritlecitinib in 22 patients with severe AA stratified by prior JAK inhibitor exposure, distinguishing JAK inhibitor-naïve patients from those previously treated with baricitinib [22]. Nine patients (40.9%) were JAK inhibitor-naïve, whereas 13 (59.1%) had previously received baricitinib for a median of 19 months before switching to ritlecitinib [22]. The two groups had comparable baseline SALT scores, but JAK inhibitor-naïve patients were significantly younger (median 14 vs. 38 years; p = 0.0143) and had a shorter duration of the current disease episode (median 20 vs. 68 months; p = 0.0138). A marked divergence in treatment response emerged at W24 [22]. In the JAK inhibitor-naïve group, all patients achieved SALT50, while 7/9 (77.8%) reached both SALT ≤ 20 and SALT75, and 5/9 (55.6%) achieved SALT90. Moreover, all patients with baseline eyebrow or eyelash involvement showed improvement in both EBA and ELA scores [22]. By contrast, efficacy was substantially more limited among JAK inhibitor-experienced patients: only 3/13 (23.1%) achieved SALT50, and 1/13 (7.7%) reached SALT75 and SALT90. Although 4/13 (30.8%) were classified as achieving SALT ≤ 20, three of these patients had already been in this range at the time of ritlecitinib initiation, indicating that clinically meaningful additional benefit after switching was modest in most cases [22]. Nevertheless, the study also showed that switching from baricitinib to ritlecitinib may still be beneficial in selected patients. Indeed, three baricitinib-experienced patients achieved reductions in more than 25 SALT points after the switch, despite previous relapse or incomplete response under baricitinib [22]. Importantly, no worsening of SALT score from baseline was observed over the 24-week follow-up in either group, and no treatment-related AEs were reported among the 22 included patients [22].

In a further single-center real-world study from China, Sheng et al. evaluated ritlecitinib 50 mg once daily in 35 patients with severe AA followed for 24 weeks [23]. The cohort was relatively young (median age 23.0 years) and had a high baseline disease burden, with a median SALT score of 92.0, eyebrow involvement in 80.0%, eyelash involvement in 71.4%, and nail abnormalities in 14.3% of cases. Most patients had received previous treatments (94.3%), including prior JAK inhibitor exposure in 45.7%, and 82.9% received combination therapy during follow-up [23]. Clinical responses increased over time. At W12, 11.4% of patients achieved SALT ≤ 20, 8.6% reached SALT ≤ 10, and 5.7% achieved complete scalp regrowth; by W24, these proportions increased to 40.0%, 22.9%, and 11.4%, respectively [23]. Eyebrow and eyelash outcomes also improved, although with different magnitudes: at W24, eyebrow response was observed in 21.4% of patients, whereas eyelash response reached 48.0% [23]. Baseline factors associated with a lower probability of achieving SALT ≤ 20 at W24 included younger age, longer current disease duration, and higher baseline SALT score, while patients with complete scalp hair loss at baseline were overrepresented among nonresponders [23]. The safety profile was acceptable overall. The most frequent AE was folliculitis (34.2%), followed by upper respiratory infections, urticaria, and dyslipidaemia (11.4% each); less common abnormalities included mild liver function test alterations and hematological changes, with no serious AEs or treatment discontinuations reported [23].

A further single-center real-world study specifically explored the early efficacy of ritlecitinib in 25 patients with moderate AA (baseline SALT 21–49) treated with 50 mg once daily for at least 16 weeks [24]. The cohort had a median age of 29 years, a median baseline SALT score of 35.0, and relatively limited extra-scalp involvement, with eyebrow and eyelash involvement reported in 28.0% and 12.0% of patients, respectively. Previous systemic therapy had been used in a minority of patients, including baricitinib in 16.0% and systemic corticosteroids in 24.0%, while some patients continued or initiated concomitant intralesional or topical corticosteroid therapy during follow-up [24]. Clinical responses were already detectable at W8 and improved further by W16. Specifically, 28.0% of patients achieved SALT50, 8.0% achieved SALT75, and 40.0% reached SALT ≤ 20 at W8; by W16, these rates increased to 68.0%, 36.0%, and 76.0%, respectively [24]. Consistently, the median SALT score declined from 35.0 at baseline to 15.0 at W16. The study also suggested that baseline serum IgE may have predictive value, as patients who failed to achieve SALT50 by W16 had significantly higher IgE levels, whereas no other baseline characteristics showed significant differences [24]. Ritlecitinib was generally well tolerated. One patient developed elevated liver enzymes at W16, which resolved after treatment discontinuation, and one additional patient developed dyslipidaemia; no other relevant AEs were reported [24].

3.2.3. Special Populations

In a single-center retrospective real-world study focused on adolescents, Franzese et al. evaluated ritlecitinib 50 mg once daily in 11 patients aged ≥12 years with moderate-to-severe AA and baseline SALT ≥ 50, all treated for at least 24 weeks without concomitant systemic or topical therapies [25]. The cohort had a mean age of 16.0 ± 1.3 years, a mean baseline SALT score of 86.8 ± 18.5, and a mean duration of the current disease episode of 3.3 ± 2.1 years, indicating a population with substantial baseline disease burden [25]. Previous treatments were common, including topical agents in 81.8% of patients and systemic corticosteroids in 90.9%, while smaller proportions had previously received cyclosporine, dupilumab, upadacitinib, or tofacitinib [25]. Clinical improvement was evident early and progressed over time. Mean SALT score decreased significantly from baseline as early as W8 (p < 0.001), reaching a mean value of 32.8 at W24. By W24, 3/11 patients (27.3%) achieved SALT ≤ 10 and 5/11 (45.5%) reached SALT ≤ 20, indicating near-complete or substantial scalp regrowth, respectively [25]. Improvement was also observed in extra-scalp involvement: among patients with baseline eyebrow disease, 6/7 (85.7%) showed at least a 1-point improvement in ClinRO score, while eyelash improvement occurred in 4/6 patients (66.7%). Ritlecitinib was well tolerated. No serious AEs or clinically relevant laboratory abnormalities were reported, and only two patients experienced mild gastrointestinal discomfort or headache during the first month, both resolving spontaneously without treatment discontinuation [25].

In a retrospective real-world study focused on children under 12 years of age, Wang et al. evaluated ritlecitinib in 18 patients with severe AA, including alopecia totalis and alopecia universalis, treated for at least 3 months [26]. The cohort included an equal number of males and females, with a mean age at treatment initiation of 8.0 years and a very high baseline disease burden, reflected by a median baseline SALT score of 99.9 [26]. Mean age at onset was 3.8 years, and prior treatments included topical and oral corticosteroids, topical minoxidil, upadacitinib, and glycyrrhizin. Eleven patients received ritlecitinib monotherapy, whereas seven received concomitant topical halometasone [26]. Overall, 55.6% of patients (10/18) achieved the primary outcome of SALT ≤ 20 at the last follow-up. Response appeared to be more favorable in patients with less extreme baseline severity: among those with severe AA (SALT 50–94), 85.7% responded, whereas only 36.4% of those with extremely severe disease (SALT 95–100) achieved response [26]. Across the whole cohort, 83.3% achieved SALT50 and 66.7% achieved SALT75. Moreover, among the 14 patients with eyebrow or eyelash involvement at baseline, nine achieved at least a 2-grade improvement in ClinRO assessment [26]. No significant differences in response rates were observed between monotherapy and combination therapy, or between severity groups, although the small sample size limits these comparisons [26]. Baseline disease characteristics appeared to influence outcomes. Responders had significantly shorter overall disease duration (2.9 vs. 4.8 years; p = 0.02), shorter duration of the current episode (19.4 vs. 40.0 months; p = 0.006), and lower baseline SALT scores (80.35 vs. 97.36; p = 0.001) than nonresponders [26]. Eyebrow involvement was also more common among nonresponders (p = 0.007), whereas age, sex, eyelash involvement, nail disease, and atopic or autoimmune comorbidities were not significantly associated with treatment response [26]. Ritlecitinib was generally well tolerated. AEs were mild and included urticaria, headache, hypertriglyceridaemia, transient transaminase elevation, and elevated creatine kinase, with no major safety signals emerging during follow-up [26].

Further pediatric real-world evidence comes from a retrospective case series that included 10 children aged ≤11 years treated with ritlecitinib for at least 12 weeks [27]. The mean age at treatment initiation was 8.7 years, and the cohort included a heterogeneous spectrum of disease severity, with mild AA in 10.0% of cases, moderate AA in 50.0%, and severe AA in 40.0%; alopecia universalis was present in 30.0% of patients, while eyebrow or eyelash involvement and nail changes were each reported in 40.0% and 50.0%, respectively [27]. Previous systemic therapy was uncommon, being reported in one patient each for corticosteroids and tofacitinib, although most children received concomitant topical treatment during follow-up [27]. Clinical improvement became more evident over time. Mean SALT score decreased from 52.8 at baseline to 37.5 at W12 and to 8.6 at W24. At W12, 40.0% of patients had already achieved SALT ≤ 20, whereas among the seven children evaluable at W24, all reached SALT ≤ 20 and 71.0% achieved at least 80% SALT improvement. At the end of follow-up, complete scalp hair regrowth was observed in 50.0% of the overall cohort [27]. Improvement in extra-scalp involvement was also reported, with three of four children with baseline eyebrow/eyelash hair loss achieving at least a 2-grade ClinRO improvement by W24 [27]. Ritlecitinib was generally well tolerated. Mild AEs included acute urticaria in two patients and folliculitis in one, while laboratory findings remained within normal limits throughout follow-up. Moreover, two patients discontinued treatment because of remission, although one later relapsed after 2 months [27].

3.2.4. Refractory Disease and Switch Strategies

A further real-world study specifically evaluated ritlecitinib as a switch strategy in 18 patients with AA refractory to prior JAK inhibitor therapy, including tofacitinib in 66.7% of cases and baricitinib in 33.3% [28]. The cohort had a mean age of 23.9 years, a mean baseline SALT score of 68.1 ± 30.2 at ritlecitinib initiation, and a long disease course, with a median duration of the current episode of 36 months; eyebrow or eyelash alopecia was present in 61.1% of patients [28]. Before switching, patients had received their prior JAK inhibitor for a median of 10.5 months, with all classified as treatment failures: 55.6% had shown no response and 44.4% only an insufficient response. After transitioning to ritlecitinib 50 mg once daily, clinical improvement was progressive but not immediate [28]. Mean SALT score decreased from 68.1 at baseline to 50.1 at W12 and to 37.1 at W24. At W24, 61.1% of patients achieved at least a 30% SALT improvement, 22.2% reached at least 80% improvement, and 16.7% achieved complete scalp regrowth [28]. Importantly, 44.4% achieved SALT ≤ 20 and 27.8% reached SALT ≤ 10 by W24, indicating that a clinically meaningful proportion of patients derived benefit despite prior failure of another JAK inhibitor [28]. Treatment was generally well tolerated. AEs were reported in 44.4% of patients, but all were mild to moderate and included acne, urticaria, weight gain, fatigue, and headache, with no severe safety signals described [28].

3.2.5. Comparative Real-World Evidence

In a monocentric retrospective real-world study, Foggia et al. compared the clinical, trichoscopic, and safety outcomes of baricitinib, ritlecitinib, and upadacitinib in 56 patients with moderate-to-severe AA treated for at least 24 weeks [29]. Nineteen patients received ritlecitinib, 20 baricitinib, and 17 upadacitinib. Baseline demographic and clinical characteristics were generally comparable across groups, including baseline SALT scores, although all patients treated with upadacitinib and half of those treated with baricitinib had concomitant atopic dermatitis [29]. All three JAK inhibitors were associated with significant within-group clinical improvement over time. In the ritlecitinib group, mean SALT score decreased from 87.85 at baseline to 58.73 at W16 and 41.98 at W24, a trajectory closely resembling that observed with baricitinib and slightly less favorable numerically than that seen with upadacitinib [29]. However, no statistically significant between-group differences in SALT score were detected at either W16 or W24, indicating broadly comparable short-term efficacy across the three treatments. Trichoscopic activity also improved in all groups, with a reduction in inflammatory markers such as black dots, broken hairs, and exclamation mark hairs, alongside progressive regrowth features [29]. These changes were numerically more rapid and more pronounced with upadacitinib, but ritlecitinib also showed a clear parallel improvement in scalp disease activity over the observation period [29]. The safety profile was favorable overall. In the ritlecitinib group, the most frequent AEs were upper respiratory tract infection (15.8%), creatine phosphokinase elevation (15.8%), acne (10.5%), and headache (5.3%). No serious AEs or treatment discontinuations were reported in any treatment group [29].

4. Discussion

The present narrative review provides a comprehensive overview of the currently available evidence regarding the effectiveness and safety of ritlecitinib in patients with AA, with a particular focus on real-world clinical data. Post hoc analyses and real-world studies were considered as complementary but distinct sources of evidence, with the former providing data from more controlled trial-derived settings and the latter reflecting outcomes observed in routine clinical practice. Overall, the available literature suggests that ritlecitinib is associated with clinically meaningful hair regrowth across a broad spectrum of AA phenotypes, including severe disease, pediatric populations, and patients previously exposed to other systemic therapies. Importantly, emerging real-world studies appear to largely confirm the efficacy signals previously observed in randomized clinical trials. One of the most consistent findings emerging from the available evidence is the progressive nature of treatment response with ritlecitinib. Both clinical trial analyses and real-world studies demonstrate that clinical improvement tends to increase over time, with higher response rates observed at later follow-up timepoints [17,18,20,21,23]. Longitudinal analyses from the ALLEGRO clinical trial program showed a progressive shift in SALT score distribution toward lower disease severity categories over a 24-month period, indicating sustained efficacy with continued treatment. Similarly, real-world studies reported increasing proportions of patients achieving clinically meaningful responses, such as SALT ≤ 20 or ≥80% improvement in SALT score, between early and later follow-up assessments. These findings suggest that ritlecitinib may require sufficient treatment duration to achieve maximal clinical benefit, a pattern that appears consistent with other JAK inhibitors used in AA.

Real-world evidence further highlights the heterogeneity of treatment responses among patients with AA. Several studies reported distinct response kinetics, with some individuals demonstrating early improvements within the first weeks of therapy, while others exhibit a more gradual response trajectory. This variability likely reflects the complex pathophysiology of AA and the influence of multiple disease-related factors, including baseline severity, disease duration, and prior treatment exposure. In particular, lower baseline SALT scores and shorter disease duration have been reported in several studies as factors potentially associated with better treatment outcomes. These observations may support the concept that earlier intervention with targeted immunomodulatory therapies could improve clinical outcomes by preventing prolonged follicular immune activation and irreversible follicular miniaturization. However, these associations were not uniformly observed across all cohorts and should therefore be interpreted with caution [19,20,23,24,26]. In addition, the retrospective design of most studies and differences in baseline severity, prior treatment exposure, concomitant therapies, and follow-up duration may have influenced these associations.

Another important aspect emerging from the reviewed studies concerns the impact of prior JAK inhibitor exposure. Several real-world analyses suggest that patients naïve to JAK inhibitor therapy tend to achieve higher response rates compared with those previously treated with other agents in this class [21,22,28]. For example, studies comparing ritlecitinib outcomes in JAK inhibitor–naïve versus baricitinib-experienced patients demonstrated substantially greater response rates in the naïve population [22]. Nevertheless, clinically meaningful improvement may still occur in selected patients who switch to ritlecitinib after inadequate response to another JAK inhibitor [22,28]. These findings indicate that ritlecitinib may still represent a viable therapeutic option in certain refractory cases, although the magnitude of response may be attenuated in heavily pre-treated populations.

Real-world data also provide valuable insights into treatment outcomes across specific patient subgroups that are often underrepresented in randomized clinical trials. In particular, pediatric populations represent a clinically relevant subgroup in AA, as disease onset frequently occurs during childhood or adolescence. Available observational studies suggest that ritlecitinib may be effective and well tolerated in both adolescents and younger children, with several reports describing substantial hair regrowth and favorable safety outcomes [25,26,27]. Although these preliminary findings are encouraging, the limited number of patients and the retrospective nature of the available studies highlight the need for larger prospective investigations to better characterize treatment responses and long-term safety in pediatric populations.

In addition to scalp hair regrowth, several studies reported improvements in extra-scalp manifestations of AA, including eyebrow and eyelash involvement. These findings are clinically relevant, as involvement of these areas is often associated with more severe disease and greater psychosocial burden. The available data suggest that ritlecitinib may contribute to improvements in these manifestations in a meaningful proportion of patients, although response rates may differ between scalp and non-scalp hair [18,20,21,22,25,26,27].

From a safety perspective, the overall tolerability profile of ritlecitinib appears favorable and generally consistent across both clinical trials and real-world settings. Most reported AEs were mild to moderate in severity and included acne, folliculitis, upper respiratory tract infections, headache, and transient laboratory abnormalities [18,19,20,21,23,24,25,26,27,28,29].

However, safety findings should be interpreted cautiously, as AE collection and reporting were not standardized across real-world studies, follow-up durations were generally limited, and small sample sizes reduce the ability to detect uncommon or delayed AEs. Importantly, serious AEs and treatment discontinuations due to safety concerns were uncommon in the available studies [18,19,20,21,23,24,25,26,27,28,29]. These findings are in line with the safety profile observed in the ALLEGRO clinical trial program and support the use of ritlecitinib as a targeted systemic therapy for patients with moderate-to-severe AA. Nevertheless, continued pharmacovigilance and longer-term real-world studies remain necessary to better define the long-term safety profile of this therapy.

Comparative real-world evidence remains limited but provides preliminary insights into the relative performance of different JAK inhibitors in AA. The few available studies comparing ritlecitinib with other agents, such as baricitinib and upadacitinib, suggest broadly comparable short-term clinical outcomes; however, these findings should be considered hypothesis-generating rather than definitive conclusions regarding comparative effectiveness [29]. Moreover, some analyses have reported numerically faster response kinetics with certain agents, although these findings should be interpreted cautiously due to small sample sizes and potential confounding factors. Future head-to-head studies or larger comparative real-world cohorts will be important to clarify potential differences in efficacy, safety, and treatment persistence among currently available JAK inhibitors [30,31,32].

Despite the growing body of evidence on ritlecitinib in AA, several limitations should be acknowledged when interpreting the findings of this review. First, the majority of available real-world studies are retrospective in design and involve relatively small sample sizes, which may limit the generalizability of their findings. These design features may also increase the risk of selection bias, information bias, and residual confounding, particularly in the absence of controlled comparisons. In addition, publication bias cannot be excluded, as early real-world reports may preferentially describe clinically relevant, positive, or otherwise noteworthy experiences. Second, there is substantial heterogeneity across studies in terms of patient populations, baseline disease severity, outcome definitions, and follow-up durations, which complicates direct comparisons between studies. Third, many real-world reports include variable treatment approaches, including concomitant therapies or variable treatment durations, which may influence observed outcomes. Furthermore, the relatively recent introduction of ritlecitinib into clinical practice means that long-term real-world data remain limited, particularly regarding sustained efficacy, relapse rates after treatment discontinuation, and long-term safety outcomes. Finally, the narrative design of this review did not allow for formal risk-of-bias assessment or quantitative synthesis of the available data.

Overall, the currently available evidence suggests that ritlecitinib represents an effective and generally well-tolerated therapeutic option for patients with alopecia areata across a range of clinical scenarios, including severe disease and selected refractory cases. Real-world data largely confirm the efficacy observed in clinical trials and provide additional insights into treatment response dynamics, predictors of response, and outcomes in specific patient populations. However, further prospective real-world studies with larger cohorts and longer follow-up are needed to better define the optimal positioning of ritlecitinib within the therapeutic algorithm of AA and to clarify its long-term effectiveness and safety profile.

5. Conclusions

Ritlecitinib represents a promising targeted therapeutic option for patients with alopecia areata, with growing evidence supporting its effectiveness and favorable safety profile in both clinical trials and real-world settings. Available data suggest progressive and clinically meaningful hair regrowth across a broad spectrum of disease severity, including pediatric populations and patients with prior treatment failure.

However, treatment response appears heterogeneous and influenced by baseline disease characteristics, particularly disease severity and duration, highlighting the importance of early and appropriate patient selection.

Despite encouraging results, current real-world evidence remains limited by heterogeneity in study design, small sample sizes, and relatively short follow-up durations.

Further large-scale, prospective, and long-term real-world studies are warranted to better define predictors of response, optimize treatment strategies, and clarify the long-term safety and durability of ritlecitinib in routine clinical practice.