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An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.

ABSTRACT: Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ?2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common ?-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ?50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.

SUBMITTER: Jabbari A

PROVIDER: S-EPMC6564681 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.

Jabbari A A Sansaricq F F Cerise J J Chen J C JC Bitterman A A Ulerio G G Borbon J J Clynes R R Christiano A M AM Mackay-Wiggan J J

The Journal of investigative dermatology 20180213 7

Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small ...[more]

PMID: 29452121

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Project description:ImportanceAlopecia areata (AA) is characterized by nonscarring hair loss of the scalp, face, and/or body. Alopecia totalis (AT) and alopecia universalis (AU) involve complete loss of the scalp and body hair, respectively. The epidemiology of AA in the US remains unclear, having previously been extrapolated from older studies that were limited to specific geographic areas or clinical settings, or from self-reported data.ObjectiveTo estimate the annual prevalence and incidence of AA and AT and/or AU (AT/AU) in the US.Design, setting, and participantsThis retrospective, population-based cohort study was conducted from January 2016 to December 2019 and included enrollees in the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental databases and their dependents, with plan enrollment during each study calendar year and the year prior.ExposuresPrevalent cases were identified by 1 or more claims for AA or AT/AU (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L63.x, L63.0, L63.1) during each year of interest or the year prior. Incident cases were identified by 1 or more claims for AA or AT/AU during a specific year and no diagnosis the year prior.Main outcomes and measuresAnnual incidence and prevalence rates were calculated and stratified by age, sex, and region. National employer-sponsored insurance population estimates were obtained using population-based weights.ResultsAmong eligible patients (2016: n = 18 368 [mean (SD) age, 40.6 (17.9) years; 12 295 women (66.9%)]; 2017: n = 14 372 [mean (SD) age, 39.6 (17.7) years; 9195 women (64.0%)]; 2018: n = 14 231 [mean (SD) age, 38.9 (17.3) years; 8998 women (63.2%)]; 2019: n = 13 455 [mean (SD) age, 39.1 (17.4) years; 8322 women (61.9%)]), AA prevalence increased from 0.199% (95% CI, 0.198%-0.200%) in 2016 to 0.222% (95% CI, 0.221%-0.223%) in 2019. Roughly 5% to 10% of prevalent and incident cases of AA were AT/AU. The prevalence of AT/AU increased from 0.012% (95% CI, 0.012%-0.013%) to 0.019% (95% CI, 0.018%-0.019%) from 2016 to 2019. Incidence of AA per 100 000 person-years ranged from 87.39 (95% CI, 86.84-87.96) in 2017 to 92.90 (95% CI, 92.35-93.45) in 2019. Incidence of AT/AU ranged from 7.09 (95% CI, 6.94-7.25) in 2017 to 8.92 (95% CI, 8.75-9.09) in 2016. Prevalence and incidence of AA and AT/AU were higher among female vs male individuals, adults vs children and adolescents, and in the Northeast vs other regions.Conclusions and relevanceThe results of this cohort study suggest that these recent AA prevalence and incidence estimates could help improve current understanding of the disease burden. Further research is warranted to elucidate subpopulation differences and trends in AA in the broader US population.

Project description:BackgroundAlopecia areata (AA) is an autoimmune disease characterized by hair loss mediated by CD8+ T cells. There are no reliably effective therapies for AA. Based on recent developments in the understanding of the pathomechanism of AA, JAK inhibitors appear to be a therapeutic option; however, their efficacy for the treatment of AA has not been systematically examined.MethodsThis was a 2-center, open-label, single-arm trial using the pan-JAK inhibitor, tofacitinib citrate, for AA with >50% scalp hair loss, alopecia totalis (AT), and alopecia universalis (AU). Tofacitinib (5 mg) was given twice daily for 3 months. Endpoints included regrowth of scalp hair, as assessed by the severity of alopecia tool (SALT), duration of hair growth after completion of therapy, and disease transcriptome.ResultsOf 66 subjects treated, 32% experienced 50% or greater improvement in SALT score. AA and ophiasis subtypes were more responsive than AT and AU subtypes. Shorter duration of disease and histological peribulbar inflammation on pretreatment scalp biopsies were associated with improvement in SALT score. Drug cessation resulted in disease relapse in 8.5 weeks. Adverse events were limited to grade I and II infections. An AA responsiveness to JAK/STAT inhibitors score was developed to segregate responders and nonresponders, and the previously developed AA disease activity index score tracked response to treatment.ConclusionsAt the dose and duration studied, tofacitinib is a safe and effective treatment for severe AA, though it does not result in a durable response. Transcriptome changes reveal unexpected molecular complexity within the disease.Trial registrationClinicalTrials.gov NCT02197455 and NCT02312882.FundingThis work was supported by the US Department of Veterans Affairs Office of Research and Development, National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institutes of Health grant R01 AR47223 and U01 AR67173, the National Psoriasis Foundation, the Swedish Society of Medicine, the Fernström Foundation, the Locks of Love Foundation, the National Alopecia Areata Foundation, and the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research.

Dataset Information

An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.

Publications

An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.

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