LITFULOTM (Ritlecitinib) Capsules: A Janus Kinase 3 Inhibitor for the Treatment of Severe Alopecia Areata.

LITFULOTM (ritlecitinib) capsules were recently approved for the treatment of severe alopecia areata in adolescents and adults, aged ≥12 years. Ritlecitinib is the active ingredient and a dual inhibitor of Janus kinase 3 and the tyrosine kinase expressed in hepatocellular carcinoma kinase family. It prevents immune attack on the hair follicles that leads to hair loss. In a phase 2b-3 dose-dependant study, five doses of oral ritlecitinib and placebo administered once daily (QD) were investigated. Ritlecitinib demonstrated efficacy in achieving the primary outcome, Severity of Alopecia Tool (SALT) score of ≤20, at week 24 (31% [38/124] 200-mg ritlecitinib QD for 4 weeks, then 50 mg QD for 20 weeks; 22% [27/121] 200-mg ritlecitinib QD for 4 weeks, then 30 mg QD for 20 weeks; 23% [29/124] 50-mg ritlecitinib QD; 14% [17/119] 30-mg ritlecitinib QD; 2% [1/59] 10-mg ritlecitinib QD; and 2% [2/130] placebo). Mild to moderate common adverse effects were observed, which included headache, nasopharyngitis, and upper respiratory tract infection. The recommended regimen of ritlecitinib capsules is 50 mg QD with without food and swallowed whole.

Effectiveness and Predictive Factors of Response to Tofacitinib Therapy in 125 Patients with Alopecia Areata: A Single-centre Real-world Retrospective Study.

Alopecia areata is an autoimmune disorder that greatly impacts patients' quality of life, and its management remains challenging. Tofacitinib is the first Janus kinase inhibitor to be approved for clinical use and is the most extensively studied. Several studies have demonstrated the clinical effectiveness of oral tofacitinib in treating patients with alopecia areata. However, despite being widely used in clinical practice, no prospective randomized controlled trials have been implemented and its indication criteria have not been thoroughly established. Moreover, little is known about the factors associated with response to therapy under real-world conditions. The aims of this retrospective cohort study of patients with alopecia areata treated with tofacitinib for 3 months were to assess the effectiveness of tofacitinib and to identify predictive factors of response to it. Primary outcome was the change in disease severity, as evaluated by Severity of Alopecia Tool (SALT) grade. A total of 125 patients with alopecia areata were included, the incidence of effectiveness was 83.2%, and 16.0% of patients achieved a result of complete remission. Total duration of alopecia areata and previous hair regrowth were independent predictors of response. Combined therapy was associated with relapse after discontinuation. No severe adverse event was observed. This study suggests that tofacitinib provides an effective treatment option for patients with alopecia areata, and that earlier intervention in the treatment of severe alopecia areata with tofacitinib may lead to better outcomes.

Drug Survival and Long-term Outcome of Tofacitinib in Patients with Alopecia Areata: A Retrospective Study.

Several non-randomized clinical trials and retrospective studies have demonstrated encouraging efficacy and well-tolerated safety of tofacitinib in the treatment of alopecia areata. However, there are scarce data on a large cohort of patients with alopecia areata in long-term real-world practice. This single-centre, retrospective, observational cohort study included 126 patients with alopecia areata treated with tofacitinib between February 2021 and December 2022. The aims of this study are to evaluate drug survival, effectiveness and safety of tofacitinib for treatment of alopecia areata, and to identify potential factors influencing long-term outcomes. Median duration of treatment was 23.00 (interquartile range (IQR) 15.00, 47.25) weeks. Median all-cause survival time of 126 patients treated with tofacitinib was 44 weeks (95% confidence interval (95% CI) 36.3, 51.7), and the all-cause drug retention rate at 12 weeks, 24 weeks and 48 weeks were 90.0%, 66.4% and 42.3%, respectively. The most common reason for discontinuation was complete remission/satisfaction. A total of 80 patients treated with tofacitinib for over 6 months were included in the efficacy analysis, the overall complete response rate at 24 weeks was 33.8% (27/80). No life-threatening serious adverse events occurred. Sex is an independent risk factor in predicting patient outcomes. This real-world study confirmed the high effectiveness and acceptable safety profile of tofacitinib in alopecia areata, with a satisfactory drug survival rate, and provides supporting data for the clinical application of tofacitinib in Chinese patients with alopecia areata.

A Retrospective Review of Anthralin in Petrolatum in the Treatment of Alopecia Areata in the Pediatric Population.

BACKGROUND/OBJECTIVES: Alopecia areata (AA) is a T-cell driven autoimmune disease, which results in hair loss. This study aims to determine the efficacy, tolerability and safety of different concentrations of anthralin in the treatment of pediatric AA. METHODS: A retrospective cohort study of patients < 18 yo diagnosed with AA treated with anthralin at SickKids Hospital, Toronto dermatology outpatient clinic in 2016 - 2018. Anthralin used at 0.1%, 0.2%, 0.5% and 1% in petrolatum at short contact, at increments of 15 minutes every week until a 1 hr maximum contact achieved. No other treatment was used in conjunction. Severity of Alopecia Tool (SALT) scores (SS) were determined using photographs and descriptions to assess severity of alopecia at baseline and post anthralin treatment. RESULTS: A total of 11 charts were reviewed in this retrospective cohort. Hair loss pattern; 3 patients with patchy, 6 had mixed (patchy and ophiasis), and 2 were totalis. All except for 1 patient had failed traditional treatments. One patient had complete hair regrowth, 3 showed more than 85% hair re-growth and 7 patients showed more than 75% hair regrowth, the average time for this to occur was 6.5 months. None of the patients experience serious side effects. CONCLUSIONS: Our study demonstrated the efficacy and tolerability of topical anthralin 0.1% to 1% in pediatric alopecia areata. In our study, anthralin 0.2% appears to offer the best performance and tolerability profile among the different concentrations used, with treatment course of at least 6 months in order to achieve more than 75% hair regrowth.

Major improvement of very severe alopecia areata in patients treated with the combination of baricitinib and low doses of corticosteroids: an eight-case series.

Alopecia areata (AA), especially very severe types, causes patients severe psychological and social distress. Although baricitinib alone has been shown to be effective in conferring complete hair regrowth (HR) in severe AA [Severity of Alopecia Tool (SALT) score 50-94], it gave poor therapeutic results in very severe AA (SALT score ≥ 95). Methotrexate alone is similarly ineffective, but in a recent study of patients with areata totalis or universalis, low-dose prednisone with methotrexate gave a 20% rate of HR, and was effective and well tolerated. In our study of baricitinib 4 mg + prednisone 20 mg per day tapered over 3 months to treat eight women with very severe AA, seven of eight achieved complete HR (SALT score 0) and one had partial HR (SALT score 30).

Safety of Janus Kinase inhibitors in Patients with Alopecia Areata: A Systematic Review.

BACKGROUND AND OBJECTIVES: Janus kinase (JAK) inhibitors are emerging as a therapeutic option for alopecia areata. The risk of potential adverse events is currently debated. In particular, several safety data for JAK inhibitors are extrapolated from a single study in elderly patients with rheumatoid arthritis treated with tofacitinib or adalimumab/etanercept as a comparator. The population of patients with alopecia areata is clinically and immunologically different from persons with rheumatoid arthritis and tumor necrosis factor (TNF) inhibitors are not effective in these patients. The objective of this systematic review was to analyze available data on the safety of various JAK inhibitors in patients with alopecia areata. METHODS: The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was performed by searching PubMed, Scopus and EBSCO databases with the last search on March 13, 2023. RESULTS: In total, 36 studies were included. The frequency and odds ratio (OR) for most common adverse events versus placebo were: for baricitinib hypercholesterolemia (18.2% vs 10.5%, OR = 1.9) and headache (6.1% vs 5.1%, OR = 1.2), for brepocitinib elevated creatinine level (27.7% vs 4.3%, OR = 8.6) and acne (10.6% vs 4.3%, OR = 2.7), for ritlecitinib acne (10.4% vs 4.3%, OR = 2.6) and headache (12.5% vs 10.6%, OR = 1.2) and for deuruxolitinib headache (21.4% vs 9.1%, OR = 2.7) and acne (13.6% vs 4.5%, OR = 3.3). The respective numbers for upper respiratory infections were: baricitinib (7.3% vs 7.0%, OR = 1.0) and brepocitinib (23.4% vs 10.6%, OR = 2.6); for nasopharyngitis: ritlecitinib (12.5% vs 12.8%, OR = 1.0) and deuruxolitinib (14.6% vs 2.3%, OR = 7.3). CONCLUSIONS: The most common side effects of JAK inhibitors in patients with alopecia areata were headache and acne. The OR for upper respiratory tract infections varied from over 7-fold increased to comparable to placebo. The risk of serious adverse events was not increased.

Selective Delivery of Tofacitinib Citrate to Hair Follicles Using Lipid-Coated Calcium Carbonate Nanocarrier Controls Chemotherapy-Induced Alopecia Areata.

Chemotherapy-induced alopecia (CIA) is one of the common side effects in cancer treatment. The psychological distress caused by hair loss may cause patients to discontinue chemotherapy, affecting the efficacy of the treatment. The JAK inhibitor, Tofacitinib citrate (TFC), showed huge potential in therapeutic applications for treating baldness, but the systemic adverse effects of oral administration and low absorption rate at the target site limited its widespread application in alopecia. To overcome these problems, we designed phospholipid-calcium carbonate hybrid nanoparticles (PL/ACC NPs) for a topical application to target deliver TFC. The results proved that PL/ACC-TFC NPs showed excellent pH sensitivity and transdermal penetration in vitro. PL/ACC NPs offered an efficient follicular targeting approach to deliver TFC in a Cyclophosphamide (CYP)-induced alopecia areata mouse model. Compared to the topical application of TFC solution, PL/ACC-TFC NPs significantly inhibited apoptosis of mouse hair follicles and accelerated hair growth. These findings support that PL/ACC-TFC NPs has the potential for topical application in preventing and mitigating CYP-induced Alopecia areata.

A child with generalized hypertrichosis due to secondary topical minoxidil exposure.

Hypertrichosis is defined as excessive hair growth anywhere on the body in either males or females. It may be caused by genetic conditions, endocrinological disorders, exposure to specific medications (including phenytoin, minoxidil and diazoxide) and other less frequent causes. We report the case of a 1-year-old boy with a family history of thyroid disease and alopecia areata who presented with generalized hypertrichosis due to secondary exposure to topical minoxidil. We discuss an uncommon cause of hypertrichosis and the importance of considering a wide differential diagnosis.

Dupilumab Induced Hair Regrowth in Alopecia Totalis.

Alopecia Areata (AA) is an autoimmune process that results in varying degrees of hair loss. Currently, there is no single treatment that has proven to be efficacious in a large cohort of patients. Dupilumab, a human monoclonal antibody recently approved for the treatment of atopic dermatitis, may be a potential treatment option for patients with treatment resistant AA. J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.6254 Citation: Bur D, Kim K, Rogge M. Dupilumab induced hair regrowth in alopecia totalis. J Drugs Dermatol. 2023;22(4):410-412. doi:10.36849/JDD.6254.

Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis.

The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.

Culprits of Medication-Induced Telogen Effluvium, Part 1.

Telogen effluvium (TE) is a common clinical consequence of medication-related alopecia. The inciting cause of TE may be difficult to identify due to delays in clinically apparent hair loss. Because medication-induced TE is a nonscarring alopecia that typically is reversible, appropriate management requires identification of the underlying triggering medication and cessation of it, if possible. In part 1 of this series, we review the existing literature on medication-induced TE with a focus on systemic retinoids, antifungal agents, and psychotropic medications.