Upadacitinib for management of recalcitrant alopecia areata: A retrospective case series

To the Editor: We read with interest the recent paper by Youssef et al,1Youssef S. Bordone L.A. Effective treatment of alopecia universalis with oral upadacitinib.JAAD Case Rep. 2022; 31: 80-82https://doi.org/10.1016/j.jdcr.2022.08.014Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar which reported the complete resolution of alopecia universalis in a 67-year-old man who was treated with upadacitinib, a selective oral janus kinase 1 inhibitor. An additional 6 previous cases have been published on the use of upadacitinib in patients with alopecia areata (AA).2Bourkas A.N. Sibbald C. Upadacitinib for the treatment of alopecia areata and severe atopic dermatitis in a paediatric patient: A case report.SAGE Open Med Case Rep. 2022; 102050313X221138452https://doi.org/10.1177/2050313X221138452Crossref PubMed Scopus (4) Google Scholar, 3Cantelli M. Martora F. Patruno C. Nappa P. Fabbrocini G. Napolitano M. Upadacitinib improved alopecia areata in a patient with atopic dermatitis: A case report.Dermatol Ther. 2022; 35: e15346https://doi.org/10.1111/dth.15346Crossref PubMed Scopus (29) Google Scholar, 4Asfour L. Getsos Colla T. Moussa A. Sinclair R.D. Concurrent chronic alopecia areata and severe atopic dermatitis successfully treated with upadacitinib.Int J Dermatol. 2022; 61: e416-e417https://doi.org/10.1111/ijd.16316Crossref PubMed Scopus (9) Google Scholar, 5Gambardella A. Licata G. Calabrese G. De Rosa A. Alfano R. Argenziano G. Dual efficacy of upadacitinib in 2 patients with concomitant severe atopic dermatitis and alopecia areata.Dermatitis. 2021; 32: e85-e86https://doi.org/10.1097/DER.0000000000000780Crossref PubMed Scopus (23) Google Scholar, 6Gori N. Cappilli S. Di Stefani A. Tassone F. Chiricozzi A. Peris K. Assessment of alopecia areata universalis successfully treated with upadacitinib.Int J Dermatol. 2023; 62: e61-e63https://doi.org/10.1111/ijd.16342Crossref PubMed Scopus (6) Google Scholar Five patients had comorbid, moderate-to-severe atopic dermatitis (AD), which was the primary indication for treatment with upadacitinib.2Bourkas A.N. Sibbald C. Upadacitinib for the treatment of alopecia areata and severe atopic dermatitis in a paediatric patient: A case report.SAGE Open Med Case Rep. 2022; 102050313X221138452https://doi.org/10.1177/2050313X221138452Crossref PubMed Scopus (4) Google Scholar, 3Cantelli M. Martora F. Patruno C. Nappa P. Fabbrocini G. Napolitano M. Upadacitinib improved alopecia areata in a patient with atopic dermatitis: A case report.Dermatol Ther. 2022; 35: e15346https://doi.org/10.1111/dth.15346Crossref PubMed Scopus (29) Google Scholar, 4Asfour L. Getsos Colla T. Moussa A. Sinclair R.D. Concurrent chronic alopecia areata and severe atopic dermatitis successfully treated with upadacitinib.Int J Dermatol. 2022; 61: e416-e417https://doi.org/10.1111/ijd.16316Crossref PubMed Scopus (9) Google Scholar, 5Gambardella A. Licata G. Calabrese G. De Rosa A. Alfano R. Argenziano G. Dual efficacy of upadacitinib in 2 patients with concomitant severe atopic dermatitis and alopecia areata.Dermatitis. 2021; 32: e85-e86https://doi.org/10.1097/DER.0000000000000780Crossref PubMed Scopus (23) Google Scholar, 6Gori N. Cappilli S. Di Stefani A. Tassone F. Chiricozzi A. Peris K. Assessment of alopecia areata universalis successfully treated with upadacitinib.Int J Dermatol. 2023; 62: e61-e63https://doi.org/10.1111/ijd.16342Crossref PubMed Scopus (6) Google Scholar All 7 patients had substantial improvement in AA with upadacitinib 30 mg daily. In January 2022, upadacitinib received approval from the Food and Drug Administration for the treatment of moderate-to-severe AD.2Bourkas A.N. Sibbald C. Upadacitinib for the treatment of alopecia areata and severe atopic dermatitis in a paediatric patient: A case report.SAGE Open Med Case Rep. 2022; 102050313X221138452https://doi.org/10.1177/2050313X221138452Crossref PubMed Scopus (4) Google Scholar However, clinical trials have not yet been conducted to investigate upadacitinib as a potential therapy for AA. In this letter, we report 3 cases of recalcitrant AA that were successfully treated with upadacitinib to contribute to the supporting evidence for this therapy (Table I).Table ISummary of 3 patients who received upadacitinib for treatment of alopecia areataCaseAge (ys) and SexComorbidConditionsDisease Duration, y∗Unless specified otherwise.Locations of AAClinical Course of AAPrevious TherapiesAdjuvant Therapies for AAUPA Daily Dose and DurationResponse to UPA137 FNone12Scalp, eyebrows, and eyelashesRR with AT on the scalp in 2012 and persistent ophiasis AADPCP, PRED, MS, ILTAC, SADBE, MTX, TTFB, and BEDMTX (until 3 mo on UPA)UPA 30 mg × 5 mo, then 15 mg for 3 moComplete hair regrowth on the scalp227 MAD24Scalp, eyebrows, and eyelashesRR on the scalp, with complete loss of eyebrow hair for 12 yrsTTFB, BED, and ILTACNoneUPA 30 mg × 3 moComplete hair regrowth on the scalp, partial transient regrowth of the eyebrows362 FAD, liver cirrhosis7 moScalp and eyebrowsRP with 90% hair loss at baselinePREDNoneUPA 30 mg × 4 moComplete regrowth of hair on the scalp and eyebrowsAA, Alopecia Areata; AD, atopic dermatitis; AT, alopecia totalis; BED, bimatoprost eye drops; DPCP, diphenylcyclopropenone; ILTAC, intralesional triamcinolone acetonide; MS, minoxidil solution; MTX, methotrexate; PRED, prednisone; RP, rapidly progressing; RR, relapsing-remitting; SADBE, squaric acid dibutylester; TTFB, topical tofacitinib; UPA, upadacitinib.∗ Unless specified otherwise. Open table in a new tab AA, Alopecia Areata; AD, atopic dermatitis; AT, alopecia totalis; BED, bimatoprost eye drops; DPCP, diphenylcyclopropenone; ILTAC, intralesional triamcinolone acetonide; MS, minoxidil solution; MTX, methotrexate; PRED, prednisone; RP, rapidly progressing; RR, relapsing-remitting; SADBE, squaric acid dibutylester; TTFB, topical tofacitinib; UPA, upadacitinib. Our patients underwent medical screening before starting upadacitinib and had laboratory investigations performed every 3 months, which included a complete blood cell count, liver enzymes, and a lipid panel. One patient had preexisting alcohol-related liver cirrhosis with portal hypertension and a history of jaundice and ascites. At baseline, her gamma-glutamyl transferase was mildly elevated, but her blood work was otherwise normal. After consultation with her hepatologist, her liver cirrhosis was deemed sufficiently stable to start upadacitinib. Complete resolution of AA on the scalp occurred in all 3 patients after 3 to 8 months on upadacitinib. Upadacitinib was well-tolerated, with only 1 patient developing mild acne and no other adverse effects. The duration of AA before starting upadacitinib ranged from 7 months to 24 years. In our first case, the patient had complete resolution of her ophiasis AA, a notoriously challenging subtype of AA to treat (Fig 1). She had tried numerous other interventions before upadacitinib, including oral methotrexate 20 mg weekly for >5 years, which stabilized her AA but did not provide sufficient improvement in her ophiasis AA. The second patient had a history of relapsing-remitting AA since the age of 3 years on the scalp, eyebrows, and eyelashes (Fig 2). He discontinued upadacitinib after 3 months, due to the loss of private insurance coverage. At the 7-month follow-up, his AA on the scalp was fully resolved and he reported partial transient regrowth of the eyebrows, which relapsed a few weeks stopping upadacitinib. Our third patient had rapidly progressing AA and presented with approximately 90% hair loss from the scalp at baseline (Fig 3). After 4 months on upadacitinib, she had complete hair regrowth on the scalp.Fig 2Treatment of alopecia areata on the scalp using upadacitinib 30 mg daily in a 27-year-old man with comorbid atopic dermatitis. A to C, At baseline, he had patches of hair loss on the frontal scalp, parietal scalp, and temporal scalp above the ears. He took upadacitinib 30 mg daily for 3 months and then stopped. D to F, At 7 months since initiation of upadacitinib and approximately 4 months since he stopped taking the medication, he had complete regrowth of the patches of hair loss on the scalp.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3Treatment of alopecia areata on the scalp with upadacitinib 30 mg daily in a 62-year-old woman with comorbid atopic dermatitis and liver cirrhosis. A and B, At baseline, she had near-total hair loss on the scalp after developing rapidly progressing AA over the preceding 7 months. C and D, After 4 months on upadacitinib, she had complete regrowth of the hair on her scalp and eyebrows.View Large Image Figure ViewerDownload Hi-res image Download (PPT) All 3 patients had previously tried at least 1 other therapy for AA, and 2 patients had suboptimal responses to multiple different treatments. Two of our patients had comorbid AD, which completely cleared on upadacitinib, alongside their hair regrowth. Our results indicate that upadacitinib may be an important consideration for the management of recalcitrant AA, especially in patients with comorbid AD. Further studies in randomized controlled trials are warranted to evaluate the efficacy of upadacitinib in treating AA. Dr Johnston does not have any potential conflicts of interest to disclose. Dr Poelman has served as a consultant and has received honoraria for speaking engagements from AbbVie, Amgen, Bausch Health, Janssen, Novartis, and Sandoz, and has conducted research for AbbVie, Bausch Health, and Janssen.

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