New targeted therapeutic approaches (eg. biologics, small molecules) have significantly changed the management of inflammatory dermatology conditions in recent years. Alopecia areata (AA), a non-scarring autoimmune hair loss condition, is one of the latest diseases to benefit from these developments. Here we review traditional, new and evolving therapies for AA and highlight the benefits, challenges and uncertainties that come with these new options. We present various real-world data collection approaches currently available and introduce GRASS-UK/GRASS-International as a global collaborative network of prospective AA disease registers designed to study the longer-term safety and effectiveness of new AA therapies as they are introduced.

BACKGROUND:Fibrosing alopecia in a pattern distribution (FAPD) is a lymphocytic primary cicatricial alopecia first described in 2000. However, to date, the FAPD literature remains sparse. OBJECTIVES:To identify clinicopathological features and treatment outcomes of FAPD in a large multicentre cohort. METHODS:Patients who had biopsy-proven FAPD were selected from nine specialist hair clinics and were reviewed retrospectively to evaluate the clinical pattern of hair loss, trichoscopic and histopathological features, and response to treatment. RESULTS:Of 110 patients, with a mean age of onset of 52.5 (SD 14.8) years, 94 (85.5%) were women. The most common trichoscopic findings were loss of follicular ostia (97.2%, 103/106) and anisotrichia (97%, 84/87). Histopathological examination revealed perifollicular lymphocytic infiltration in 96.1% (99/103) and concentric lamellar fibrosis in 97% (92/95). After a median duration of treatment of 24 [interquartile range (IQR) 13-50] months, there was stabilization in hair density [median Sinclair grade 3.0 (IQR 3.0-4.0) pretreatment vs. 3.0 (IQR 2.0-4.0) post-treatment, P = 0.62]. Out of the 42 patients who received treatment for ≥ 12 months, 23 achieved stabilization and 16 demonstrated improvement in hair density. CONCLUSIONS:Limitations of the study include its retrospective design and disparate treatments. FAPD may be prone to misdiagnosis because of overlapping clinicopathological features with androgenetic alopecia. A combination of anti-inflammatory (for example, topical corticosteroids) and hair growth-promoting agents (for example, topical or low-dose oral minoxidil) can stabilize the condition or even promote hair regrowth.

Abstract Photodynamic therapy (PDT) is an established field treatment for actinic keratoses of the scalp. Expected adverse effects include pain, erythema, oedema and crusting, with occasional transient shedding. Permanent alopecia is rarely reported. Fibrosing alopecia in a patterned distribution (FAPD) is an uncommon lymphocytic cicatricial alopecia that combines features of female pattern hair loss (FPHL) and lichen planopilaris or frontal fibrosing alopecia. A 74-year-old woman with Fitzpatrick type II skin underwent scalp PDT for biopsy-proven moderate actinic keratosis. The treatment was complicated by an exaggerated inflammatory reaction with severe pain and pruritus, prolonged erythema and crusting, and secondary skin-swab-proven Staphylococcus aureus infection requiring oral antibiotics and topical corticosteroids. Within weeks she developed abrupt diffuse shedding and persistent loss of density without regrowth. She reported only mild gradual thinning beforehand. There were a 2-cm frontal hairline recession, midfrontal and vertex thinning (Sinclair grade 5) with patchy vertex involvement, perifollicular erythema and scale, and focal loss of follicular ostia. Blood tests were normal, including full blood count, ferritin, folate, vitamin B12, vitamin D, liver function tests and erythrocyte sedimentation rate. Paired horizontal and vertical biopsies showed follicular miniaturization consistent with FPHL together with perifollicular lamellar fibrosis, loss of sebaceous glands and a chronic lymphocytic infiltrate targeting the infundibulum and isthmus, supporting FAPD. The symptoms improved with clobetasol propionate scalp application, hydroxychloroquine and low-dose oral minoxidil, but hair density has not recovered. Published reports linking PDT to FAPD are lacking. This case supports the hypothesis that intense postprocedural inflammation may precipitate or accelerate FAPD in predisposed individuals. Persistent shedding after PDT should not be assumed to be telogen effluvium. Perifollicular inflammation or loss of ostia should prompt early trichoscopy, biopsy and anti-inflammatory treatment. Preprocedure counselling and a low threshold for ­follow-up may help limit irreversible hair loss in at-risk patients.

We report an uncommon presentation of alopecia areata (AA) characterized by multiple hair shafts displaying segmental heterochromia and calibre change. The pigmentary and calibre changes suggest an intermittent low-level inflammatory process in diffuse AA, with periods of recovery where the hair fibre regains its normal characteristics.

The data is captured in routine clinical care assessing the safety and efficacy of patients using a new therapy in our centre. It's standard for us to audit new therapies in this way and additional ethics is not required.

Abstract Randomized controlled trials (RCTs) of Janus kinase inhibitors (JAKis), including ritlecitinib, have demonstrated efficacy in alopecia areata (AA). However, strict eligibility criteria limit generalizability, excluding many patients treated in clinical practice. There is a need for structured real-world data to capture disease characteristics, treatment patterns and outcomes beyond clinical trial extension studies. The Global Register of Alopecia Areata Disease Severity and Treatment Safety-UK (GRASS-UK) is a prospective observational register addressing this gap. In its pilot phase, 45 patients have been recruited from two UK centres (Salford Royal Hospital, and Mersey and West Lancashire Hospital). The cohort is predominantly female (71%), with age range 6–73 years, and is largely of White British ethnicity (80%). Nearly half (49%) are aged ≥ 40 years while adolescents (aged 12–20 years) and children (1–11 years) are also represented (11% and 4%, respectively). Disease is long-standing, with 47% reporting AA for ≥ 10 years. Disease severity is high, with 80% having severe or very severe disease (Severity of Alopecia Tool ≥ 50%), including 36% with alopecia totalis or alopecia universalis. Clinically relevant comorbidities are frequently reported, including eczema (18%), thyroid disease (9%), anxiety/depression (9%) and prior malignancy (7%). Previous treatments include systemic immunosuppressants (15%), topical immunotherapy (13%) and JAKis (7%). Current management reflects contemporary practice. Ritlecitinib is used in 44% of patients, with 9% awaiting initiation and 7% receiving another JAKi. Other therapies include systemic immunosuppressants (4%) and diphencyprone (22%). Intralesional or topical corticosteroids are used in 20% and adjunctive minoxidil in 18%. GRASS-UK captures a clinically complex and treatment-experienced population with AA, under-represented in RCTs and extension studies, highlighting the importance of complementary real-world evidence. Early pilot findings demonstrate the feasibility and clinical value of structured national data collection. Expansion into phase I will enhance data completeness and enable longitudinal analyses to better define real-world effectiveness, safety and treatment pathways in AA.

ImportanceFrontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.ObjectiveTo identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.Design, Setting, and ParticipantsFour genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci.Main Outcomes and MeasuresGenome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci.ResultsOf 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5′ untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10−8). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles.Conclusions and RelevanceIn this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

Misleading or ineffective advice at early stages of alopecia may negatively impact those receiving it, as early detection and treatment are important to minimize the progression and psychological impact of the condition. Understanding the support- and information-seeking behaviour of people with alopecia prior to diagnosis is essential to support effective decision making at this critical time. We surveyed 85 patients with alopecia areata, female pattern hair loss and frontal fibrosing alopecia attending a specialist hair clinic. This study focuses on the actions taken by these patients when their hair loss started and before they received professional medical advice. Patients could complete a paper survey or fill in a survey online (via SurveyMonkey). Ethical approval was obtained from the London – Surrey Research Ethics Committee. Participants described their hair loss episode and how they initially sought advice, and then rated this advice on a five-point Likert scale (very unhelpful, generally unhelpful, neutral, some help, very helpful). Participants could also share their experiences in free-text boxes. Eighty-one participants gave responses detailing their initial reaction to noticing hair loss, with 85% (n = 69) sharing feelings of distress, shock or fear. Commonly expressed was a desire for an explanation. The internet was the most utilized source of information (n = 49), with 73% receiving ‘helpful’ advice and 14% receiving ‘unhelpful’ advice. Patients generally found the internet a good source of information, helping some realize their diagnosis. However, a common experience was the volume of information available feeling ‘overwhelming’ and being unsure what to trust, as well as the large number of products on sale. Hairdressers were the second most solicited source of advice (n = 38); 47% said they were helpful, whereas 34% received unhelpful advice. Some felt their hairdresser gave no useful information or recommended ineffective products to them. Positive experiences were hairdressers providing wigs and signposting to healthcare professionals. Fewer participants used social media (n = 20) and Alopecia UK (n = 15), but when used these resources were rated as helpful (70% and 73%, respectively). Specifically, the ability to connect with others in a similar situation and gain practical advice were valued. These data show the dramatic emotional impact of hair loss when it first occurs, and that various resources are used by patients to help understand their situation. Hairdressers may represent an area for improving the information available to people: signposting with booklets or support group information, or having additional training in recognizing these conditions. Social media and support groups can be effective at supporting patients, but trustworthy resources such as Alopecia UK are underutilized, and would benefit from greater awareness.

Importance:Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets. Objective:To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci. Design, Setting, and Participants:Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci. Main Outcomes and Measures:Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci. Results:Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5' untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10-8). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles. Conclusions and Relevance:In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

There have been major advances in the treatment of severe alopecia areata (AA) in recent years, but less progress in treating mild-to-moderate disease. Here, we report the results of a multicentre phase II randomized controlled trial of dithranol, formulated in a novel topical vehicle incorporating a silicon nanoparticle controlled-release mechanism, in patients with mild-to-moderate AA. Patients with patchy active AA of ≥ 6 months’ duration and a Severity of Alopecia Tool (SALT) score < 50 were randomized to 0.25%, 0.5%, 1% or 2% dithranol or placebo applied once daily for 6 months, with a follow-up visit at 8 months. The primary endpoint was ≥ 30% reduction in SALT score at 6 months, with secondary endpoints including a 60% reduction in SALT and change in quality-of-life scores (Alopecia Areata Symptom Impact Scale and Alopecia Areata-Quality of Life Index). In total, 155 patients with AA were randomized, of whom 97 had mild disease (SALT < 20) and 58 had moderate disease (SALT 20–49). Of these, 106 patients (68%) completed the treatment phase of the trial; dropouts were equally distributed across the five groups. The primary endpoint response rate in the full analysis set (n = 155) was 76% in the dithranol 1% group, compared with 37% in the placebo group (P < 0.01). A 60% reduction in SALT score was seen in 30%, 40%, 58% and 50% of patients applying dithranol 0.25%, 0.5%, 1% and 2%, respectively, compared with 19% in patients applying the placebo. Skin irritation on the scalp was common in patients applying dithranol, although in most it was mild in degree and only weakly related to the dithranol concentration. Twenty patients (16%) using dithranol withdrew from the study due to skin irritation. Irritation was more common during the early stages of treatment and by 6 months it was reported by only five patients (6%). Eleven patients (9%) using dithranol reported temporary skin discoloration. There were no serious or unexpected adverse events. The use of dithranol to treat AA was first reported in 1935. Sporadic reports of its efficacy have appeared since, but there are no previous randomized placebo-controlled trials. The results reported here indicate that a novel dithranol formulation is an effective treatment for patients with mild-to-moderate AA. The results also raise the possibility that the efficacy of dithranol in treating AA is not related to its irritancy. Further work is needed to establish the best treatment protocol. The study was sponsored and funded by Soterios Pharma.

Alopecia areata (AA) is an autoimmune condition that often coexists with other immune-mediated inflammatory diseases (IMIDs) such as Crohn disease, atopic dermatitis, vitiligo and others. The inflammatory and therapeutic overlap between these conditions offers a unique opportunity for drug repositioning, guiding treatment choices and enabling holistic patient management. However, the limited number of drugs licensed for AA presents a significant challenge. We systematically reviewed current and emerging therapies for AA by analysing clinical trials registered on ClinicalTrials.gov. This was complemented by cross-referencing approved therapeutic options in IMIDs commonly associated with AA, including atopic dermatitis (eczema), psoriasis, Crohn disease, rheumatoid arthritis (RA) and multiple sclerosis. For eczema, therapies such as dupilumab show limited evidence in also treating AA. However, Janus kinase inhibitors, a growing class of treatments, offer promise for both conditions. For instance, baricitinib is licensed for both AD and AA, while upadacitinib is licensed for AD and is currently in phase III trials for AA. Amlitelimab, which targets the OX40 ligand pathway, is currently in phase III clinical trials for atopic dermatitis and in phase II trials for severe AA. In Crohn disease, upadacitinib is licensed and has shown potential in phase III trials for AA. In psoriasis, overlapping therapies include ustekinumab, approved for psoriasis and being studied for AA. As for patients with RA, tofacitinib is approved for moderate-to-severe disease and is also utilized in AA. Abatacept is a cytotoxic T lymphocyte-associated protein 4 (CTLA4) immunoglobin costimulatory modulator that attenuates the activation of T cells and is widely used in RA. AA genome-wide association studies have demonstrated that CTLA4 is a susceptibility gene in AA, and phase II trials with abatacept in AA have shown promising results. As for future directions, the development of cross-specialty IMID multidisciplinary team meetings may be valuable, given the rapid introduction of emerging therapies and the resulting complexity. Additionally, integrating real-world evidence is critical, and registries play an essential role in generating insights into drug safety and efficacy across diverse populations. The Global Registry of Alopecia areata disease Severity and treatment Safety (GRASS) UK is a prospective, multicentre, observational clinical registry designed to create harmonized datasets. These datasets aim to generate high-quality, real-world data on existing and emerging therapies for AA, ultimately improving patient care and outcomes.

A 37-year-old woman with a history of recently regrown patchy alopecia areata (AA) presented with increased hair shedding and hair colour changes. She had observed intermittent bands of lighter hair colour within otherwise normal black hairs. The patient had a history of atopy and was diagnosed with iron deficiency 3 years prior, treated with supplementation, but ferritin levels were normal at the time of presentation. She denied dyeing her hair. Trichoscopy and light microscopy revealed sections of lighter hair colour along individual hair shafts associated with decreased calibre of the fibre within these areas. Strikingly, the hair fibres returned to normal diameter where her normal black hair colour resumed. Segmented heterochromia describes lighter bands of colour along the same hair shaft and is mainly associated with intermittent iron deficiency anaemia. However, changes in hair calibre are not described in this condition. In contrast, the combination of lighter hair pigmentation and reduced hair shaft calibre is sometimes observed close to the scalp in some longer hairs affected by AA. In 1984 Shuster coined the term ‘coudability’ to describe the sign of easy hair shaft kinking in these hairs when they are pushed towards the scalp (Shuster S. ‘Coudability’: a new physical sign of alopecia areata, Br J Dermatol 1984; 111: 629). The name is derived from the elbow-shaped bend in the affected area of the hair, reminiscent of tip of a coude urinary catheter. We present this case as an uncommon variant of the coudability hair, where the ‘on–off’ changes observed represent the effects of an intermittent low-level inflammatory process on the hair follicle on a background of diffuse AA. Observation of this sign suggests ongoing disease activity and should prompt additional therapy to prevent disease progression.

Context:Low-dose oral minoxidil (LDOM) can safely and effectively treat numerous hair disorders. Reported doses range from 0.25 mg to 5 mg daily titrated against clinical effectiveness and adverse events. Some clinicians advocate routine monitoring of patients treated with LDOM. However, there is limited evidence on whether minoxidil in such small doses adversely impacts patients with normal hemodynamic and biochemical baseline profiles. Aims:The aim of the study is to evaluate the need for regular monitoring of patients treated with LDOM. Subjects and Methods:This is a retrospective analysis of patients treated with LDOM in a tertiary hair clinic between April 2017 and June 2020. The clinical and laboratory parameters were assessed every 6 months. On commencing LDOM, baseline blood pressure, heart rate, and weight were recorded, and renal and liver function tests were performed. Statistical Analysis:The data were analyzed using graphical exploration. Results:The heart rate, weight, renal function, and liver function appeared stable throughout the treatment course. The weight and estimated glomerular filtration rate showed a trend to increase over time, but these findings were not statistically significant for any of the outcomes. Conclusions:The data support the position that routine monitoring is not required during treatment in asymptomatic patients with normal baseline values. Regular monitoring of blood pressure, heart rate, weight as well as liver and kidney function is not required during treatment with LDOM in patients with normal hemodynamic and biochemical baseline profiles. Patients with preexisting renal impairment can be prescribed oral minoxidil; however, we advocate ongoing monitoring in this subgroup, especially those with moderate-to-advanced disease. To the best of our knowledge, this is the first study that provides longitudinal monitoring data for LDOM with a follow-up period beyond 6 months and up to 36 months on treatment.

BACKGROUND:As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA. OBJECTIVES:To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA. METHODS:Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process. The final stage was held as a virtual meeting facilitated via Zoom. The consensus threshold was set at ≥66%. RESULTS:Of 365 questions, expert consensus was achieved in 204 (56%) questions following completion of the three rounds. Three additional questions were included at the final meeting. The category with the strongest consensus agreement was disease monitoring (9; 100%). Questions pertaining to physical therapies achieved the least category consensus (15; 40%), followed by systemic therapy (45; 43%). LIMITATIONS:The study lacked sufficient representation from Africa and South America. CONCLUSIONS:SOFFIA highlights areas of agreement and disagreement among experts. Robust research is warranted to provide evidence-based treatment recommendations.

ABSTRACT Alopecia areata (AA) is an inflammatory hair loss disorder caused by an immune‐mediated attack of the hair follicle (HF) bulb. Active disease is characterised by a peribulbar proinflammatory infiltrate, HF immune privilege collapse and premature catagen induction, yet the underlying drivers of AA remain poorly understood. With comparable autoimmune inflammatory conditions displaying metabolic alterations, we hypothesised that AA is marked by similar pathobiological changes. To investigate this, we utilised an exploratory metabolomics‐based discovery liquid chromatography mass spectrometry (LC–MS) approach. This yielded 32 putatively annotated metabolites significantly altered between lesional and nonlesional AA scalp. Notably, 13‐HODE, a linoleic acid metabolite linked to vascular function, was decreased, whilst uric acid (UA), a purine degradation metabolite linked to vascular dysfunction, was increased in the lesional scalp. Moreover, serum LC–MS revealed elevated UA in AA compared to controls, which is linked to systemic endothelial dysfunction. CD31+/ICAM‐1+ immunofluorescence co‐expression analysis revealed elevated vascular inflammation and endothelial cell activation in the AA scalp. We also experimentally provoked the same response in ex vivo human HF culture via UA or fructose (which increases UA) supplementation. Interestingly, the fructose‐generating polyol pathway enzymes, AKR1B1 and SORD, are expressed in the HF, with significantly increased AKR1B1 immunoreactivity in lesional AA HFs, suggesting that fructose can be locally generated by the HF and may contribute to elevated UA levels in AA. Together, these metabolic changes point towards UA‐linked microvascular dysfunction in AA, inviting exploration of whether strategies to improve endothelial function and regulate UA are effective in managing AA.

Alopecia areata (AA), female pattern hair loss (FPHL) and frontal fibrosing alopecia (FFA) are three types of hair loss in which patients may benefit from comprehensive and complex treatment decisions in secondary and tertiary dermatology centres to prevent progression of hair loss, promote regrowth and access specialist therapies. Patients face various barriers that delay access to National Health Service dermatology assessment and personalized therapies. In this study we surveyed 85 patients with AA, FPHL and FFA attending a specialist hair clinic regarding their treatment and referral pathway from general practitioner (GP) assessment into hospital care. Patients were offered the option to complete a paper copy or fill in the survey online (via SurveyMonkey). Ethical approval was obtained from the London-Surrey Research Ethics Committee. Full responses were received from 82 patients, 76 (93%) of whom were female. In terms of ethnicity, 89% reported as White, 7% Asian and 4% Black or mixed. The majority of respondents were diagnosed with AA (59%). Patients reported various barriers to early treatment of alopecia, including delay in access to specialist dermatology care. In the sample surveyed, 88% stated that the first healthcare professional seen was their GP, with median waiting time of 2 months [interquartile range (IQR) 2–6] before their first medical visit. About 61% tried over-the-counter or home remedies before seeing their healthcare professional. Unfortunately, only 30% felt they were given the correct diagnosis by their GP, with just 26% happy with the explanation given on their first encounter. Only 35% reported receiving alopecia treatment by their GP, and 95% of patients felt they were not offered any psychological support. Furthermore, 41% experienced difficulty in getting a referral from their GP to see a dermatologist, with a median waiting time of 12 months (IQR 12–24) before seeing a dermatologist. In comparison, on their first dermatologist visit, 78% felt they were given the correct diagnosis, 82% received treatment for their alopecia, 66% were happy with the care and explanation given and 61% reported no difficulty getting referral from their first dermatologist to a specialist hair clinic. The median waiting time before first being seen in the specialist hair clinic since hair loss was 3 years (IQR 3–5). Overall, this study showed that patients faced various challenges including accurate initial diagnosis, limited treatment options and delays accessing appropriate dermatology care. Patients would benefit from solutions to mitigate delay around their early alopecia treatment that provide accessible and appropriate (secondary or specialist) dermatology care while taking into consideration their preferences and values.

ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA). To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss. ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study. The de novo cohort results are reported here. Patients aged ≥12 years with AA and ≥25% scalp hair loss received a daily, 4-week 200-mg ritlecitinib loading dose, followed by daily 50-mg ritlecitinib. Analyses are based on data up to the cut-off (December 2022). Efficacy outcomes included proportions of patients achieving Severity of Alopecia Tool (SALT) scores ≤20 and ≤10, Patient Global Impression of Change (PGI-C) score of ‘moderately improved’ or ‘greatly improved’ and eyebrow assessment (EBA) and eyelash assessment (ELA) response (≥2-grade improvement from baseline or normal score in patients with abnormal baseline EBA/ELA). Mean (SD) ritlecitinib exposure among the 449 de novo patients enrolled was 728.7 (273.81) days. At Month 24 (as observed), 73.5% and 66.4% of patients achieved SALT score ≤20 and ≤10; 82.4% had PGI-C response; 60.8% and 65.7% had EBA and ELA response. 86.1% of patients reported treatment-emergent adverse events (AEs); most were mild or moderate in severity, with the most frequent being positive SARS-CoV-2 test (24.2%), headache (20.8%) and pyrexia (13.0%). Rates of serious AEs, severe AEs and treatment discontinuations were 4.9%, 6.0% and 6.5%, respectively. Herpes zoster infection occurred in six patients, serious infections in four, malignancies (excluding nonmelanoma skin cancer) in three and major adverse cardiovascular events in three. In patients with AA and ≥25% scalp hair loss, ritlecitinib demonstrated clinical efficacy and had an acceptable safety profile with long-term treatment. ClinicalTrials.gov NCT04006457.