Alopecia areata flare patterns in children and young adults while on systemic tofacitinib

Abstract

To the Editor: The systemic Janus kinase inhibitor tofacitinib is a novel therapeutic that is used off-label for the treatment of alopecia areata (AA) in both children and adults.1Craiglow B.G. King B.A. Tofacitinib for the treatment of alopecia areata in preadolescent children.J Am Acad Dermatol. 2019; 80: 568-570Google Scholar, 2Castelo-Soccio L. Experience with oral tofacitinib in 8 adolescent patients with alopecia universalis.J Am Acad Dermatol. 2017; 76: 754-755Google Scholar, 3Cheng M.W. Kehl A. Worswick S. Goh C. Successful treatment of severe alopecia areata with oral or topical tofacitinib.J Drugs Dermatol. 2018; 17: 800-803Google Scholar Given that systemic tofacitinib is a relatively new treatment option, little is known about its long-term effectiveness. Previous studies have highlighted the possible transient efficacy of oral tofacitinib and the need for dose escalation or adjuvant therapy in periods of AA relapse, but it remains unclear whether there are any consistent flare patterns among patients.4Chiang A. Ortenzio F. Juhasz M.L.W. Yu V. Mesinkovska N.A. Balance of tofacitinib efficacy and disease flare in the treatment of alopecia universalis: A case report and review of the literature.JAAD Case Rep. 2018; 4: 733-736Google Scholar We report the characteristics and flare patterns of 21 pediatric and young adult patients with moderate-to-severe AA while on systemic tofacitinib (Table I). The mean consecutive time on tofacitinib was 31 months (range, 12-58 months). Most patients had severe AA with the absence of the majority of scalp hair and some with loss of body hair at the time of tofacitinib initiation. AA flare was defined as an increase in overall severity of alopecia tool (SALT) score by greater than 10%. Provoked flares occurring after tofacitinib dose de-escalation or brief discontinuation (eg, during acute illness) were excluded.Table IDemographics and flare characteristics of patients with alopecia areata on long-term systemic tofacitinibPatient characteristicsTotalPatients21Mean age at tofacitinib initiation, years (range)15.5 (6-20)Sex Male10 Female11Race/Ethnicity White, non-Hispanic15 Asian3 African American1 White, Hispanic1 Unreported1Mean consecutive time on tofacitinib, months (range)31 (12-58)SALT score at tofacitinib initiation 1-250 26-501 51-753 76-995 10012History of atopy No12 Yes9History of additional autoimmune disease No15 Yes6AA flares on tofacitinib Yes8 No13Mean time to AA flare, months (range)13.6 (10-18)Mean increase in SALT score with AA flare (range)35.95 (11-97)Mean duration of severe AA episode prior to tofacitinib, months (range) Flare11.8 (7-27) No flare15.1 (4-72)Mean age at diagnosis with AA, years (range) Flare10.3 (4-14) No flare9.3 (1-16)AA, Alopecia areata; SALT, severity of alopecia tool. Open table in a new tab AA, Alopecia areata; SALT, severity of alopecia tool. Eight patients (38.1%) had an AA flare while on daily tofacitinib therapy. Prior to the flare, patients had successful hair regrowth on tofacitinib with a mean SALT score decrease of 79.1 from initiation. The mean time to flare was 13.6 months (range, 10-18 months; Fig 1). The mean increase in the SALT score during a flare was 35.9 (range, 11-97). No patient had more than 1 flare while on therapy. When comparing the group of patients who flared while on tofacitinib to those who did not, there was no significant difference in the mean duration of the most recent severe AA episode (11.8 and 15.1 months, respectively; P = .62) or mean age at AA diagnosis (10.3 and 9.3 years, respectively; P = .67). In the setting of acute flares, 6 of 8 patients continued taking initial doses of tofacitinib (10 mg/day) and for 2 of 8 patients, the dosage increased (15 mg/day). Five patients were followed up after flare, and each had SALT scores comparable (within 5 or lower) to preflare values within 1-5 months. During flares, 2 of these patients continued tofacitinib monotherapy but with an increased dose, 2 patients were treated with a combination of oral prednisone (3-week taper starting at 60 mg and decreasing by 20 mg weekly) and intralesional Kenalog, and 1 patient was treated with intralesional Kenalog alone (Supplementary Table I available via Mendeley at https://doi.org/10.17632/7k99v7gvkg.1). Most patients tolerated tofacitinib well but several reported side effects, such as increased frequency of mild infections (4 patients) and gastrointestinal upset (3 patients). Systemic Janus kinase inhibitors are a treatment option for children and young adults with AA; however, we found that a subgroup of patients on long-term systemic tofacitinib therapy experienced AA flares during treatment. It is important for patients and families to understand that even if rapid hair regrowth is achieved initially on promising therapeutics like tofacitinib, flares are possible despite consistent therapy, given the waxing and waning nature and complex pathophysiology of AA. Patients should be informed in advance of potential decreased treatment response to tofacitinib and should be prepared to discuss dosage escalation and/or adjuvant therapy during flares in order to minimize hair loss. None disclosed.