Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Examining the Uncertainties Surrounding Exosome Therapy in Androgenetic Alopecia: A Call for Evidence-Based Practice.

Hair loss, a pervasive and often distressing condition, affects a substantial number of individuals globally. Although conventional treatments such as hair transplantation, topicals, oral medications, and injectables exist, they have limitations, including the necessity for repeated treatments, potential adverse effects, and cost barriers. Exosome therapy, an innovative and burgeoning option within regenerative medicine, offers a novel approach to hair loss treatment. Exosomes are small vesicles that are produced from the membranes of late-endosomes and secreted by cells, playing a crucial role in intercellular communication. Research on humans is limited,1-4 and animal studies have shown that exosomes derived from various cell types can stimulate hair growth, resulting in increased research and development of exosome therapy for hair loss.5 Establishing a uniform reporting method for exosome therapy is vital as research in this area continues to expand. A standardized approach to research reporting and results is essential for comprehending the underlying mechanisms, safety, and efficacy of exosome therapy. This article provides an in-depth analysis of the current state of exosome therapy for hair loss, including potential advantages, and limitations, as well as directions for future research. J Drugs Dermatol. 2024;23(3)    doi:10.36849/JDD.7603.

When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials.

BACKGROUND: Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations. OBJECTIVES: To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups. METHODS: The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported. RESULTS: Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss. CONCLUSIONS: These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.

Medication-induced hair loss: An update.

This article discusses drug-induced hair loss, which can occur with many drugs including cytotoxic agents, biologics, and immunomodulating agents, among others. It outlines the diagnosis and management of drug-induced alopecia, with a focus on recently implicated drugs.

Intradermal Delivery of Alopecia Therapeutics: Current State and Future Prospects.

BACKGROUND: Mesotherapy, a technique of transdermal microinjections of specific preparations, is increasingly used in fields such as dermatology and specifically for alopecia treatment. Its popularity stems from its ability to deliver drugs in a targeted manner while minimizing systemic side effects. OBJECTIVE: To assess and review current knowledge regarding the use of mesotherapy to deliver alopecia medications and highlight future directions for research. MATERIALS AND METHODS: The authors used research databases including PubMed and Google Scholar to identify current literature on mesotherapy and alopecia. The following search terms were used among other terms: "Mesotherapy" or "Intradermal" AND "Alopecia". RESULTS: Recent studies are promising for the intradermal delivery of dutasteride and minoxidil in the treatment of androgenetic alopecia. CONCLUSION: Although limitations exist with dutasteride and minoxidil therapies, further research regarding the preparation, delivery, and maintenance of these drugs is warranted as mesotherapy could establish this technique as a safe, effective, and viable treatment option for androgenetic alopecia.

A practical approach to the management of hair loss in patients with polycystic ovary syndrome.

Female patterned hair loss (FPHL) is a common form of androgenetic alopecia in women and is characterized by a hormonally directed diffuse hair loss on the scalp. Management of FPHL is well described in the literature; however, treatment of FPHL in patients with co-morbid polycystic ovarian syndrome (PCOS), an endocrinologic condition found in reproductive-aged women, has not yet been reviewed. Due to the different pathomechanism of the diseases and complexity of FPHL in PCOS patients, this study aimed to review current diagnosis and management approaches for hair loss in PCOS patients specifically and highlight the growing need for more research in this growing patient population.

Examining the Potential for Koebnerization and Disease Precipitation in Cicatricial Alopecias.

The treatment of primary scarring alopecias is challenging and patients may be susceptible to koebnerization. This predisposes cicatricial alopecia patients to worsening of their disease following procedural treatments or interventions. Research and recommendations surrounding the risk for koebnerization within scarring alopecias is extremely limited. Using a comprehensive literature review, we summarized the risks of procedures in potentially koebnerizing alopecias. We evaluated the risk not only with procedural treatments, but also with common elective cosmetic procedures and potentially trauma-inducing hairstyling techniques. Although additional studies are needed to better elucidate the risks of procedural treatments within primary scarring alopecia, we believe this review of the current evidence and expert insight will benefit healthcare providers and patients alike to help guide treatments in this challenging patient population. J Drugs Dermatol. 2023;22(1):29-34. doi:10.36849/JDD.6849.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Reversible Hair Loss in Lichen Planopilaris: Regrowth With Low-Dose Naltrexone and Platelet-Rich Plasma.

Lichen planopilaris (LPP) is a cicatricial alopecia that presents with patchy or diffuse hair loss at the vertex or parietal scalp. The literature has limited evidence on treatments for this challenging disease, with most reports involving small groups of patients with varied or suboptimal clinical responses. Amongst individuals who do respond to therapy and eventually achieve disease remission, hair regrowth within scarred alopecic patches is rare.1 Herein, we report a patient with biopsy confirmed LPP who demonstrated remarkable hair regrowth at a previously scarred alopecic patch after initiating low-dose naltrexone (LDN) and platelet-rich plasma (PRP), despite minimal response to 4 months of prior therapy with intralesional corticosteroids, topical clobetasol, topical minoxidil, finasteride, doxycycline, and ketoconazole shampoo. This case highlights the importance of remaining flexible and diligent in therapeutic approaches to LPP and the need for more robust literature on prognosis and treatment options for LPP patients. J Drugs Dermatol. 2022;21(6):671-673. doi:10.36849/JDD.6810.

An Analysis of Alopecia Related Content on Instagram and TikTok.

BACKGROUND: Social media platforms continue to grow in popularity and have become common sources of medical information and education for patients struggling with hair loss. OBJECTIVE: We sought to determine the characteristics of popular hair loss related content on Instagram and TikTok. METHODS: The top 9 most popular posts within 10 hair loss related hashtags on Instagram and TikTok were analyzed. Quantitative and qualitative analysis was used to evaluate posts from December 2020. The characteristic of the author, content category, and number of likes were analyzed for each post. RESULTS: Of 90 posts analyzed within Instagram, non-medical professional influencers created 66%, hair and wig companies created 29%, and medical professionals created 4%. Of 100 posts analyzed within TikTok, influencers created 38%, patients created 38%, hair and wig companies created 14%, and medical professionals created 10%. None of the top posts was created by board-certified dermatologists. LIMITATIONS: This study was limited by the extent of data that can be collected from Instagram and TikTok. CONCLUSIONS: A majority of the content promoted hair care products, services, or treatments not substantiated by evidence-based medicine. Instagram and TikTok provide new opportunities for dermatologists to educate the general population on alopecia while simultaneously correcting misinformation. J Drugs Dermatol. 2022;21(12):1316-1321. doi:10.36849/JDD.6707.

Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients.

BACKGROUND: The major concern regarding the use of low-dose oral minoxidil (LDOM) for the treatment of hair loss is the potential risk of systemic adverse effects. OBJECTIVE: To describe the safety of LDOM for the treatment of hair loss in a large cohort of patients. METHODS: Retrospective multicenter study of patients treated with LDOM for at least 3 months for any type of alopecia. RESULTS: A total of 1404 patients (943 women [67.2%] and 461 men [32.8%]) with a mean age of 43 years (range 8-86) were included. The dose of LDOM was titrated in 1065 patients, allowing the analysis of 2469 different cases. The most frequent adverse effect was hypertrichosis (15.1%), which led to treatment withdrawal in 14 patients (0.5%). Systemic adverse effects included lightheadedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%), leading to drug discontinuation in 29 patients (1.2%). No life-threatening adverse effects were observed. LIMITATIONS: Retrospective design and lack of a control group. CONCLUSION: LDOM has a good safety profile as a treatment for hair loss. Systemic adverse effects were infrequent and only 1.7% of patients discontinued treatment owing to adverse effects.

The Alopecia Areata Consensus of Experts (ACE) study part II: Results of an international expert opinion on diagnosis and laboratory evaluation for alopecia areata.

BACKGROUND: We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. OBJECTIVE: To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. METHODS: Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. RESULTS: Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). LIMITATIONS: The study had low representation from Africa, South America, and Asia. CONCLUSION: There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

A narrative review of therapies for scalp dermatomyositis.

Cutaneous involvement of the scalp is a common manifestation of dermatomyositis (DM), occurring in up to 82% of adults with DM. Scalp DM predominantly affects women and is characterized by dermatitis, alopecia, pruritus, and/or burning. While cutaneous DM negatively impacts quality-of-life, scalp symptoms in particular are often severe, debilitating, and recalcitrant to standard DM therapies. Currently, there is a paucity of guidelines to inform management of scalp symptoms in patients with cutaneous DM. In this narrative review, we summarize the treatments utilized to manage scalp DM and highlight potential areas for future research. We identified eight studies that reported on 27 treatments focused on cutaneous DM and described outcomes on scalp symptoms. A majority of the treatments were standard therapies for cutaneous DM and resulted in no or minimal improvement in scalp symptoms. Five therapies did result in complete resolution of scalp symptoms and were recommended as potential areas of future research. These included low-dose naltrexone and platelet-rich plasma, as well as two frequent and one less common therapy for cutaneous DM respectively: intravenous immunoglobulin, rituximab, and apremilast. Though the literature was not systematically assessed in this review, these findings illustrate not only that strategies for refractory scalp DM are lacking, but also that those demonstrating potential efficacy are limited by low levels of evidence. Additional studies, especially randomized controlled trials, are needed to better inform management of scalp DM.

A novel automated approach to rapid and precise in vivo measurement of hair morphometrics using a smartphone.

BACKGROUND: Although many hair disorders can be readily diagnosed based on their clinical appearance, their progression and response to treatment are often difficult to monitor, particularly in quantitative terms. We introduce an innovative technique utilizing a smartphone and computerized image analysis to expeditiously and automatically measure and compute hair density and diameter in patients in real time. METHODS: A smartphone equipped with a dermatoscope lens wirelessly transmits trichoscopy images to a computer for image processing. A black-and-white binary mask image representing hair and skin is produced, and the hairs are thinned into single-pixel-thick fiber skeletons. Further analysis based on these fibers allows morphometric characteristics such as hair shaft number and diameters to be computed rapidly. The hair-bearing scalps of fifty participants were imaged to assess the precision of our automated smartphone-based device in comparison with a specialized trichometry device for hair shaft density and diameter measurement. The precision and operation time of our technique relative to manual trichometry, which is commonly used by hair disorder specialists, is determined. RESULTS: An equivalence test, based on two 1-sided t tests, demonstrates statistical equivalence in hair density and diameter values between this automated technique and manual trichometry within a 20% margin. On average, this technique actively required 24 seconds of the clinician's time whereas manual trichometry necessitated 9.2 minutes. CONCLUSION: Automated smartphone-based trichometry is a rapid, precise, and clinically feasible technique which can significantly facilitate the assessment and monitoring of hair loss. Its use could be easily integrated into clinical practice to improve standard trichoscopy.

Laboratory Testing in Telogen Effluvium.

Telogen effluvium (TE) – a common cause of non- scarring hair loss – is managed with varying clinical protocols given the paucity of evidence-based practices.

Hair Care Professionals as Community Health Partners in Detection and Management of Alopecia: A Pilot Survey Study.

BACKGROUND: Alopecia is one of the most common diagnoses encountered by dermatologists; despite this, patients with hair loss often seek help from hair stylists prior to seeing a physician. OBJECTIVE: The purpose of this pilot survey study was to investigate hair stylists as hair loss community health partners and identify how dermatologists can potentially play a key role in cosmetology education. STUDY-DESIGN: Twenty-four New York City hair stylists completed a novel 23-item survey via email. RESULTS: When encountering hair loss in clients, stylists not formally educated about alopecia reported initially recommending their clients see a dermatologist, while those who were taught on the subject reported first recommending over the counter products as treatment. Hair stylists with alopecia training were equally as likely as those without alopecia training to believe hair styling practices do not contribute to hair loss. CONCLUSION: Our data support the need for integrated dermatologic training in cosmetology schools, particularly in the area of hair loss, with combined support of established hair instructors and dermatologists. Developing a brief curriculum regarding the fundamentals of alopecia etiology, diagnostics and therapeutics could equip hair stylists with useful evidence-based information they can use to help their clientele prevent and detect early stages of hair loss. By doing so, we can increase accessibility to quality hair care in the community and therefore streamline the process of alopecia patients getting the medical care they need. J Drugs Dermatol. 2021;20(8): 908-910. doi:10.36849/JDD.5643.

Commonly Used Over the Counter Therapies for Hair Growth in Skin of Color: An Evidenced-Based Review.

BACKGROUND: Given the immense psychosocial effects of hair loss as well as patient preference for treatment type, it is common for patients to turn to alternative medicine to improve their conditions. However, the commonly used alternative treatments can vary greatly between patients and particularly among skin of color populations. OBJECTIVE: In this work, we performed a scoping review of the evidence behind alternative topical treatments for hair loss used by skin of color patients. Methods & Materials: We conducted a comprehensive search using PubMed to identify relevant studies. RESULTS: Results show a diverse variety of hair growth products used; however, only a few are supported by randomized controlled trials, case reports, pilot studies, and animal studies with some important limitations. CONCLUSION: This information will be exceedingly useful for physicians so they may relay accurate evidence on these haircare practices to their skin of color patients. J Drugs Dermatol. 2021;20(7):726-731. doi:10.36849/JDD.5689.

Impact of Laboratory Work Up and Supplementation on Alopecia Patients: A Single-Center Retrospective Chart Review.

Evaluation of alopecia often includes laboratory testing for ferritin, thyroid stimulating hormone, vitamin D, and zinc as previous studies have found associations between non-scarring alopecia and vitamin deficiencies. These studies are limited by small sample sizes, and subsequent analyses showed conflicting results. This study aims to explore laboratory abnormalities in non-scarring alopecia and examine whether supplementation is associated with increased hair growth. A total of 131 patients completed at least two visits by a hair specialist at NYU’s Faculty Group Practice. They had quantitative hair measurements taken at each visit and laboratory tests performed at the first visit. There were 20 (15.3%) patients with abnormal lab results. The most common vitamin deficiency was ferritin (6.5%). Forty-two (32%) patients received supplementations that specifically addressed their vitamin or hormone deficiency. Multivariate regression analysis showed that supplementation did not significantly impact hair density or diameter (P=0.73; P=0.96, respectively). Baseline hair density and diameter were positively associated with change in hair density and diameter, respectively (standardized coefficient [β] 0.57, P<0.01; β 0.61, P<0.01). The number of prescribed oral medications was negatively associated with change in hair diameter (β -6.60, P=0.04). Limitations of this study include the single-center, retrospective design and the short followup interval. However, our findings suggest that vitamin supplementation may not lead to improved outcomes in non-scarring alopecia, thus limiting the utility of laboratory testing. Additional large-scale prospective studies are needed to improve our management of alopecia. J Drugs Dermatol. 2021;20(7):807-809. doi:10.36849/JDD.5886.

COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients.

Early in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects.