Treatment of moderate-to-severe alopecia areata in adolescents with baricitinib: A retrospective review of 29 patients.

To the Editor: The selective and reversible Janus kinase (JAK)-1/2 inhibitor baricitinib has been successfully used in phase II/III clinical trials to treat alopecia areata (AA) in adults.1King B. Ohyama M. Kwon O. et al.Two phase 3 trials of baricitinib for alopecia areata.N Engl J Med. 2022; 386: 1687-1699https://doi.org/10.1056/NEJMoa2110343Crossref PubMed Scopus (66) Google Scholar However, there is limited data regarding its use for AA in the adolescent population. Our study aimed to evaluate the efficacy of baricitinib for the treatment of moderate-to-severe AA in adolescents. We retrospectively reviewed the records of all adolescents (12-17 years) with moderate-to-severe AA treated with baricitinib for ≥3 months between January 2019 and February 2022. Hair loss was scored using the Severity of Alopecia Tool (SALT), with a SALT score >20 representing moderate-to-severe AA. Partial response was defined as a ≥60% reduction in SALT score from baseline; complete response was defined as full hair regrowth. Data analysis was performed using International Business Machines Corporation (IBM) SPSS V29.0. Twenty-nine adolescents (16 males and 13 females) with a median baseline SALT score of 80 (IQR 23-100) were identified (Table I). The mean age of onset of AA was 10.9 years and the mean duration of hair loss at baseline was 3.2 years. Partial or complete eyebrow and eyelash hair loss was observed in 15 (52%) and 8 (28%) patients respectively. Prior treatments included corticosteroids [topical (n = 14), intralesional (n = 11), and oral (n = 22)], topical minoxidil (n = 5), contact immunotherapy (n = 4), azathioprine (n = 1), cyclosporin (n = 2), methotrexate (n = 3) and tofacitinib [topical (n = 2), and oral (n = 2)].Table IBaseline characteristics and outcomes of 29 adolescent patients with moderate-to-severe alopecia areata treated with baricitinibOverall, n = 29Responders, n = 23Non-responders, n = 6P valueAge at treatment initiation, years, mean (SD)14.3 (1.6)14.3 (1.7)14.3 (1.6).93Sex, n (%) Males16 (55%)11 (48%)5 (83%).12 Females13 (45%)12 (52%)1 (17%).12Ethnicity, n (%) Caucasian22 (76%)17 (74%)5 (83%).63 Asian7 (24%)6 (26%)1 (17%).63Age of onset of AA, years, mean (SD)10.9 (3.9)12.0 (2.9)7.0 (5.1).004Duration of AA, years, mean (SD)3.2 (3.8)2.2 (2.2)7.3 (6.1).002Duration of current episode of AA, months, mean (SD)13.3 (18.6)9.3 (10.7)31.6 (34.4).01Baseline SALT score, median (IQR)80 (23-100)78 (41-99)96 (52-100).39Baseline severity of AA, n (%) Moderate (SALT score 21-49)8 (28%)7 (30%)1 (17%).50 Severe (SALT score 50-94)12 (41%)10 (43%)2 (33%).65 Very severe (SALT score 95-100)9 (31%)6 (26%)3 (50%).26AA subtype, n (%) Patchy13 (45%)12 (52%)1 (17%).12 Diffuse4 (14%)4 (17%)0 (0%).70 Ophiasis2 (7%)1 (4%)1 (17%).29 Alopecia totalis4 (14%)3 (13%)1 (17%).82 Alopecia universalis6 (21%)3 (13%)3 (50%).05Eyebrow hair loss, n (%)15 (52%)9 (39%)6 (100%).03Eyelash hair loss, n (%)8 (28%)5 (22%)3 (50%).17Nail involvement, n (%)12 (41%)10 (43%)3 (50%).78Atopic disease, n (%)11 (38%)9 (39%)2 (33%).79Other autoimmune disease, n (%)1 (3%)1 (4%)0 (0%).86Family history of AA, n (%)7 (24%)5 (22%)2 (33%).55Dose of baricitinib, mg, mean (SD)3.9 (1.8)4.1 (1.8)3.7 (1.7).66Dose of LDOM, mg, mean (SD)0.7 (0.5)0.7 (0.6)0.4 (0.1).24Duration of treatment with baricitinib and LDOM, months, mean (SD)9.8 (4.9)10.0 (4.8)8.8 (5.4).60Most recent SALT score, median (IQR)2.8 (0-19)0.3 (0-8)75 (35-100).001Eyebrow hair regrowth (complete or near-complete), n (%)8 (53%)7 (78%)1 (17%).02Eyelash hair regrowth (complete or near-complete), n (%)4 (50%)4 (80%)0 (0%).05AA, Alopecia Areata; LDOM, low-dose oral minoxidil; SALT, Severity of Alopecia Tool. Open table in a new tab AA, Alopecia Areata; LDOM, low-dose oral minoxidil; SALT, Severity of Alopecia Tool. Baricitinib was commenced at 1.7 mg/d (n = 8) or 3.4 mg/d (n = 21) and titrated at subsequent reviews based on response and tolerability (Supplementary File S2, available via Mendeley at https://data.mendeley.com/datasets/rmttpxkmd6). The mean final dose used was 3.9 mg/d with a mean duration of treatment of 9.8 months. All patients were treated with concurrent low-dose oral minoxidil (LDOM) (mean dose 0.7 mg/d). Twenty-three patients (79%) experienced partial or complete scalp hair regrowth, with a median percentage change in SALT score of 93% (IQR 64%-100%) (Supplementary Fig 1, available via Mendeley at https://data.mendeley.com/datasets/rmttpxkmd6). The mean time to onset of hair regrowth was 2.6 months. Among responders, complete or near-complete eyebrow and eyelash hair regrowth was observed in 78% and 80% respectively. Non-responders were treated for a mean duration of 8.8 months. Adverse effects of baricitinib were mild and included conjunctivitis (n = 1), neutropenia (n = 3), hypercholesterolaemia (n = 5), hypertriglyceridemia (n = 2), transaminitis (n = 3), and elevated serum creatinine (n = 4) (Supplementary Table III, available via Mendeley at https://data.mendeley.com/datasets/rmttpxkmd6). None of our patients required dose reduction or discontinuation of baricitinib due to adverse effects. Hair loss in adolescents can have a devastating psychological impact, even at lesser severities.2Christensen T. Yang J.S. Castelo-Soccio L. Bullying and quality of life in pediatric alopecia areata.Skin Appendage Disord. 2017; 3: 115-118https://doi.org/10.1159/000466704Crossref PubMed Scopus (24) Google Scholar Given the refractory nature of longstanding AA, early treatment may improve the long-term course of the disease.3Alkhalifah A. Alsantali A. Wang E. et al.Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis.J Am Acad Dermatol. 2010; 62 (quiz 189-90): 177-188https://doi.org/10.1016/j.jaad.2009.10.032Abstract Full Text Full Text PDF PubMed Scopus (380) Google Scholar While our findings are promising, there is limited data on the long-term safety of baricitinib in the paediatric population. To date, baricitinib has been used in preadolescents and adolescents at doses of up to 10 mg/d for 2.3 to 5.6 years to treat interferon-mediated inflammatory disorders.4Sanchez G.A.M. Reinhardt A. Ramsey S. et al.JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies.J Clin Invest. 2018; 128: 3041-3052https://doi.org/10.1172/JCI98814Crossref PubMed Scopus (308) Google Scholar,5Boyadzhiev M. Marinov L. Boyadzhiev V. et al.Disease course and treatment effects of a JAK inhibitor in a patient with CANDLE syndrome.Pediatr Rheumatol Online J. 2019; 17: 19https://doi.org/10.1186/s12969-019-0322-9Crossref PubMed Scopus (28) Google Scholar As in our cohort, adverse effects in these studies were mild. Overall, baricitinib may be a promising treatment for moderate-to-severe AA in adolescents. Our study is limited by its small sample size and retrospective design, as well as an atypical dose regimen of baricitinib. Twenty-three out of 29 patients (79.3%) received higher than approved doses for the treatment of AA in this age group. Our patients also received concomitant LDOM therapy as it has been suggested that JAK inhibitors act synergistically with oral minoxidil to promote hair regrowth in AA. Nevertheless, the majority of our patients had been on LDOM prior to baricitinib initiation without any significant hair regrowth, suggesting that the improvements seen were largely due to baricitinib. Larger prospective studies are required to further investigate the efficacy and safety of baricitinib for AA in adolescents. Dr Eisman is a principal investigator in clinical trials for Pfizer Inc, AbbVie, Arena Pharmaceuticals, Boston Pharmaceuticals, Bristol-Myers Squibb, Botanix, Dermira, Eli Lilly and company, LEO Pharma, Novartis, Regeneron, Tigermed, Suzhou Connect Biopharmaceuticals, Janssen, Kymab Ltd, Evelo Biosciences, KoBiolabs, and Avance Clinical. Dr Sinclair is the Director and Founder of Samson Medical Pty Ltd which holds patents on the use of oral minoxidil to treat hair loss disorders; is on the Pharmaceutical advisory board of Eli Lilly, Pfizer Inc, and Leo Pharmaceutical; is on the Speaker bureau of Abbvie, Novartis; is a principal investigator in clinical trials for Amgen, Novartis, Arcutis Biotherapeutics, Aerotech, Merck and Co, Celgene, Coherus BioSciences, Jannsen, Regeneron, MedImmune, Glaxo Smith Kline, Samson Clinical, Boehringer Ingelheim, Oncobiologics, Roche, Ascend, Dermira, AstraZeneca, Akesobio, Reistone Biopharma, UCB, Sanofi, Connect, Arena, Sun Pharma, Bristol Myer Squibb, and Galderma. Drs Moussa, Kazmi, Poa, Chitreddy, Rathnayake, Joseph, and Bhoyrul have no conflicts of interest to declare.