Real-world safety and clinical response of Janus kinase inhibitor upadacitinib in the treatment of hidradenitis suppurativa: A retrospective cohort study

To the Editor: Hidradenitis suppurativa (HS) is a chronic relapsing autoinflammatory disease in desperate need of novel therapeutic options.1Frew J.W. Marzano A.V. Wolk K. et al.A systematic review of promising therapeutic targets in hidradenitis suppurativa: a critical evaluation of mechanistic and clinical relevance.J Invest Dermatol. 2021; 141: 316-324.e2Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Janus kinase inhibition has been identified as a potential novel strategy in the management of HS, with ongoing clinical trials evaluating safety and efficacy.2Alavi A. Hamzavi I. Brown K. et al.Janus kinase 1 inhibitor INCB054707 for patients with moderate-to-severe hidradenitis suppurativa: results from two phase II studies.Br J Dermatol. 2022; 186: 803-813Crossref PubMed Scopus (14) Google Scholar Upadacitinib is a Janus kinase 1-selective inhibitor currently used in the treatment of inflammatory arthropathies and inflammatory bowel disease, conditions that share immunological similarities with HS.1Frew J.W. Marzano A.V. Wolk K. et al.A systematic review of promising therapeutic targets in hidradenitis suppurativa: a critical evaluation of mechanistic and clinical relevance.J Invest Dermatol. 2021; 141: 316-324.e2Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar,3Chapman S. Kwa M. Gold L.S. Lim H.W. Janus kinase inhibitors in dermatology: Part I. A comprehensive review.J Am Acad Dermatol. 2022; 86: 406-413Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar HS clinical trials are known to exclude many participants who may demonstrate the greatest need for novel therapies (such as those with greater than 20 draining tunnels); hence, real-world evidence is needed to address these knowledge gaps.4Montero-Vilchez T. Salvador-Rodriguez L. Sanchez-Diaz M. et al.Clinical Selection Criteria in New Clinical Trials of Hidradenitis suppurativa: external validity and implications on the daily clinical practice.Dermatol Ther. 2020; 33e14254Crossref Scopus (4) Google Scholar We conducted a retrospective cohort study of all patients with moderate to severe HS treated with upadacitinib monotherapy at our institution between October 2021 and May 2022. Captured data included demographic and disease specific information including lesion counts (all conducted by a single rater, JWF) and quality of life and pain scores. The study was approved by the Human Research Ethics Committee of South West Sydney Area Health Service. A total of 20 patients were identified, and their demographic and disease details are presented in Supplemental Table I, available via Mendeley https://doi.org/10.17632/fjv74v2w65.1. All patients underwent screening (HIV, hepatitis B, hepatitis C, tuberculosis, fasting lipids, creatine kinase) at baseline, with complete blood count, biochemistry, lipid, and creatine kinase levels assessed at week 4 and week 24. All patients received upadacitinib 15 mg per day until week 4, and individuals not achieving hidradenitis suppurativa clinical response (HiSCR) at week 4 were increased to upadacitinib 30 mg per day. Patients were then reviewed at weeks 12 and 24. Included patients had no surgical intervention, intralesional steroid injections, or concomitant antibiotics for the first 24 weeks of treatment. Clinical response data and representative clinical photographs are presented in Fig 1 and Supplemental Data (available via Mendeley at https://doi.org/10.17632/fjv74v2w65.1). Fifteen of 20 (75%) individuals achieved HiSCR50 at week 4, increasing to 100% at week 12 and maintained at week 24. HiSCR75 rates were obtained in 6/20 (30%) patients at week 4, increasing to 19/20 (95%) at week 12 and maintained at week 24. HiSCR90 rates were recorded in 4/20 (20%) patients at week 4 and 6/20 (30%) at week 12, and maintained at week 24 (Fig 1). International Hidradenitis Suppurativa Severity Score System scores (Supplemental Data) reduced significantly during therapy (P <.0001). Dermatology life quality index scores and pain rating scores reduced significantly (P <.0001) by week 4 of therapy (Supplemental Table I and Supplemental Data). Four of 20 (20%) individuals experienced flares (defined as any new lesion) during treatment. All individuals reported new abscesses (1 or 2 abscesses) in contrast to their previous experience of flares with smaller nodules, possibly implying a differential immunological basis for the development of abscesses compared with nodules and tunnels. One of 20 (5%) individuals experienced varicella zoster reactivation confirmed by lesional polymerase chain reaction. This was treated with oral valacyclovir 1 g, 3 times a day for 10 days with no interruption of upadacitinib therapy. Two individuals (10%) experienced mild, transient transaminitis during therapy which spontaneously resolved. Sixteen of 20 (80%) individuals demonstrated elevated creatine kinase levels at weeks 4 and 12 with no musculoskeletal symptoms or myoglobinuria. Twelve of 20 (60%) individuals received COVID vaccinations during treatment with no significant disease flares. Four of 20 (20%) individuals contracted COVID with mild symptoms and did not interrupt therapy during the illness. Three of 20 (15%) individuals had deroofing procedures undertaken after week 24 of therapy with no adverse outcomes noted postoperatively. Overall, our single-center experience of upadacitinib monotherapy for HS was positive, with high levels of clinical response and comparable rates of varicella zoster virus reactivation, transaminitis, and creatine kinase elevation seen in clinical trials for other inflammatory dermatoses.5Guttman-Yassky E. Teixeira H.D. Simpson E.L. et al.Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials.Lancet. 2021; 397: 2151-2168Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar Escalation to 30-mg dosing is strongly associated with improved outcomes in Hurley stage 3 disease. Additionally, we observed no serious adverse effects with upadacitinib for HS in the setting of COVID infection, vaccination, and adjuvant surgical intervention. Further data from larger, placebo-controlled trials are needed to validate our real-world observations. Dr Frew has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie, Azora, Novartis, and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, and Azora, and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche Posay.