Dupilumab therapy for alopecia areata in pediatric patients with concomitant atopic dermatitis

To the Editor: Alopecia areata (AA) is often refractory to conventional therapies. Dupilumab, a systemic interleukin 4 receptor blocker currently approved for atopic dermatitis (AD) in children aged >6 years, may be a potential therapy. Some case reports describe improvement with dupilumab therapy, and there is an ongoing clinical trial assessing dupilumab in adult patients with AA.1Harada K. Irisawa R. Ito T. Uchiyama M. Tsuboi R. The effectiveness of dupilumab in patients with alopecia areata who have atopic dermatitis: a case series of seven patients.Br J Dermatol. 2020; 183: 396-397Crossref PubMed Scopus (15) Google Scholar, 2Magdaleno-Tapial J. Valenzuela-Oñate C. García-Legaz-Martínez M. Martínez-Domenech Á. Pérez-Ferriols A. Improvement of alopecia areata with dupilumab in a patient with severe atopic dermatitis and review the literature.Australas J Dermatol. 2020; 61: e223-e225Crossref PubMed Scopus (4) Google Scholar, 3ClinicalTrials.govTreatment of alopecia areata (AA) with dupilumab in patients with and without atopic dermtitis (AD). ClinicalTrials.gov Identifier: NCT03359356.https://clinicaltrials.gov/ct2/show/study/NCT03359356Google Scholar A few reports show new or worsening AA with dupilumab initiation.4Chung J. Slaught C.L. Simpson E.L. Alopecia areata in 2 patients treated with dupilumab: new onset and worsening.JAAD Case Rep. 2019; 5: 643-645Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar We report the characteristics and outcomes of 16 pediatric patients with AA on dupilumab therapy (Table I; Supplemental Table I available via Mendeley at doi: 10.17632/wswm2nv4dx.3). Most had long-standing disease (median 4 years from diagnosis) and were refractory to multiple therapies before dupilumab (median 4 prior therapies). Oral steroids had failed in 12, and methotrexate failed in 9. All had concomitant AD, and 4 had asthma. Seven patients had alopecia universalis, 5 had ophiasis AA, and 4 had patchy AA.Table IDemographics of pediatric patients with alopecia areata (AA) on dupilumab and AA response to therapyPatientAge at dupilumab initiation, y (sex)Self-reported backgroundType of AA at initiationAge at AA diagnosis, yPrior therapies for AATherapies for AA while on dupilumabRelevant medical historyAge at AD diagnosis (duration, y)Highest prior SALT score recordedSALT score before initiation of dupilumabDuration of dupilumab therapy, moSALT scores at follow-up visits after dupilumab113 (F)AsianHistory (patchy)8Topical steroids, oral steroids, oral tofacitinib, intralesional steroidsOral tofacitinibIGA 3 AD8 y (5)150113 months: 06 months: 010 months: 0214 (F)African AmericanUniversalis3Topical steroids, oral methotrexate, oral steroidsIGA 2 AD11 y (3)1009854 months: 100313 (F)African AmericanOphiasis4Topical steroids, oral steroids, intralesional steroidsIGA 3 AD4 y (9)452514, ongoing1 month: 454 months: 2512 months: 048 (M)White, HispanicOphiasis5Topical steroids, oral steroids, topical anthralin, oral methotrexate, topical retinoidIGA 4 AD4 y (4)100357, ongoing7 months: 8510 (F)WhiteUniversalis3Oral steroids, topical steroids, topical tofacitinib, topical retinoid, topical anthralinIGA 3 AD, hypothyroidism4 y (6)1001003, ongoing3 months: 100613 (M)WhiteUniversalis12Topical steroids, topical squaric acid, topical tofacitinibTopical tofacitinib, oral methotrexate (1 month)IGA 3 AD12 y (1)10010014, ongoing4 months: 1008 months: 10012 months: 100715 (M)White, HispanicHistory (patchy)15Topical steroids, oral methotrexate, intralesional steroidsIntralesional steroidsIGA 3 AD, asthma10 y (5)25031, ongoing2 months: 106 months: 1011 months: 013 months: 1014 months: 1017 months: 027 months: 0816 (F)WhitePatchy11Topical steroids, intralesional steroids, minoxidilMinoxidilIGA 2 AD, asthma10 y (6)1002311, ongoing4 months: 23917 (F)WhiteHistory (universalis)10Topical steroids, minoxidil, intralesional steroids, oral tofacitinib, topical anthralin, squaric acid, oral steroidsOral tofacitinib, minoxidil, spironolactoneIGA 2 AD10 y (7)85011, ongoing4 months: 01012 (M)African AmericanHistory (ophiasis)8Topical steroids, topical retinoidIGA 4 AD, asthma7 y (5)25014, ongoing3 months: 07 months: 013 months: 01117 (F)WhiteOphiasis13Topical steroids, intralesional steroids, oral steroids, topical retinoid, oral methotrexate, oral tofacitinibIGA 3 AD, hypothyroidism3 y (14)801822 months: 181215 (M)WhiteUniversalis12Topical steroids, intralesional steroids, oral steroids, topical retinoid, oral methotrexateIGA 2 AD, asthma14 y (1)10010015, ongoing2 months: 986 months: 988 months: 9812 months: 981313 (F)WhiteOphiasis11Topical steroids, oral steroids, topical anthralin, oral methotrexate, topical tofacitinibIntermittent topicals onlyIGA 4 AD12 y (1)904521 month: 452 month: 451412 (F)White, HispanicUniversalis11Topical steroids, intralesional steroids, oral steroids, topical anthralin, topical retinoid, oral methotrexateIGA 3 AD, hypothyroidism10 y (2)10010016, ongoing5 months: 998 months: 8511 months: 501516 (M)WhitePatchy13Topical steroids, oral steroid, topical retinoid, intralesional steroids, oral methotrexateIntralesional steroidsIGA 4 AD, celiac disease8 y (8)252516, ongoing4 months: 1012 months: 01619 (F)WhiteUniversalis11Topical steroids, oral steroids, oral methotrexate, minoxidil, topical tofacitinibTopical tofacitinibIGA 3 AD16 y (3)1008511, ongoing2 months: 98AA, Alopecia areata; AD, atopic dermatitis; F, female; IGA, Investigator's Global Assessment; M, male; SALT, Severity of Alopecia. Tool. Open table in a new tab AA, Alopecia areata; AD, atopic dermatitis; F, female; IGA, Investigator's Global Assessment; M, male; SALT, Severity of Alopecia. Tool. Patients received 300 mg subcutaneous injections of dupilumab every 2 weeks. Three had mild injection site reactions. Four (patients 2, 3, 7, and 16) worsened on dupilumab initially, with an average worsening in the Severity of Alopecia Tool (SALT) score of 11.3 (1-2 months after initiation), but those with follow-up improved with time. The SALT scores in 2 patients were 0 at 12 months. Subset analysis of 6 patients with active disease at initiation and >4 months of follow-up showed that 4 (patients 3, 4, 14, and 15) experienced improvement in their AA (Fig 1; Supplemental Fig 1, available via Mendeley at doi: 10.17632/gdj2tnyz42.1), and 2 patients (6 and 12) had no/minimal improvement. Both patients with no significant improvement had SALT scores of 100 before dupilumab therapy. Of those with improvement, the average reduction in SALT score was 33.3 after 12 months. All patients with improvement had moderate to severe AD (Investigator's Global Assessment scores of 3-4) at initiation, with a lower median age at AD diagnosis and longer median duration of AD (6 years old and 6 years, respectively) compared with the nonresponders (13 years old and 1 year, respectively). Although this sample is small, these findings are consistent with prior reports showing greater likelihood of regrowth with dupilumab in patients with more severe and long-standing histories of AD.5Marks D.H. Mesinkovska N. Senna M.M. Cause or cure? Review of dupilumab and alopecia areata.J Am Acad Dermatol. June 13, 2019; https://doi.org/10.1016/j.jaad.2019.06.010Abstract Full Text PDF Google Scholar Of the 4 patients with SALT scores of 0 at the time of dupilumab initiation, 2 (patients 1 and 9) were on systemic tofacitinib for AA and tolerated decreasing doses of tofacitinib without increased hair loss, suggesting the potential use of dupilumab in dose de-escalation of oral Janus kinase inhibitors. None of the 6 patients with active disease at initiation and with ≤4 months of follow-up had experienced regrowth at the most recent follow-up. All patients, including those with only limited follow-up, had clinical improvement of their AD and asthma. Dupilumab was prescribed to pediatric patients with severe or refractory AA and concomitant AD. A subset of patients who received dupilumab experienced significant hair regrowth. Dupilumab may be a therapeutic option for AA in those when traditional therapies have failed, especially in patients with concurrent AD or asthma, for which the benefits of dupilumab are clear. Further studies with larger cohorts are needed to determine the efficacy of dupilumab for AA and the adverse effects of therapy. None disclosed.