Effectiveness and Predictive Factors of Response to Tofacitinib Therapy in 125 Patients with Alopecia Areata: A Single-centre Real-world Retrospective Study
DOI:
https://doi.org/10.2340/actadv.v103.12425Keywords:
alopecia areata, effectiveness, predictive factors, real-world, tofacitinibAbstract
Alopecia areata is an autoimmune disorder that greatly impacts patients’ quality of life, and its management remains challenging. Tofacitinib is the first Janus kinase inhibitor to be approved for clinical use and is the most extensively studied. Several studies have demonstrated the clinical effectiveness of oral tofacitinib in treating patients with alopecia areata. However, despite being widely used in clinical practice, no prospective randomized controlled trials have been implemented and its indication criteria have not been thoroughly established. Moreover, little is known about the factors associated with response to therapy under real-world conditions. The aims of this retrospective cohort study of patients with alopecia areata treated with tofacitinib for 3 months were to assess the effectiveness of tofacitinib and to identify predictive factors of response to it. Primary outcome was the change in disease severity, as evaluated by Severity of Alopecia Tool (SALT) grade. A total of 125 patients with alopecia areata were included, the incidence of effectiveness was 83.2%, and 16.0% of patients achieved a result of complete remission. Total duration of alopecia areata and previous hair regrowth were independent predictors of response. Combined therapy was associated with relapse after discontinuation. No severe adverse event was observed. This study suggests that tofacitinib provides an effective treatment option for patients with alopecia areata, and that earlier intervention in the treatment of severe alopecia areata with tofacitinib may lead to better outcomes.
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Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol 2018; 78: 1-12.
https://doi.org/10.1016/j.jaad.2017.04.1141 DOI: https://doi.org/10.1016/j.jaad.2017.04.1141
Mostaghimi A, Gao W, Ray M, Bartolome L, Wang T, Carley C, et al. Trends in prevalence and incidence of alopecia areata, alopecia totalis, and alopecia universalis among adults and children in a US employer-sponsored insured population. JAMA Dermatol 2023; 159: 411-418.
https://doi.org/10.1001/jamadermatol.2023.0002 DOI: https://doi.org/10.1001/jamadermatol.2023.0002
Toussi A, Barton VR, Le ST, Agbai ON, Kiuru M. Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review. J Am Acad Dermatol 2021; 85: 162-175.
https://doi.org/10.1016/j.jaad.2020.06.047 DOI: https://doi.org/10.1016/j.jaad.2020.06.047
Lee S, Lee WS. Management of alopecia areata: updates and algorithmic approach. J Dermatol 2017; 44: 1199-1211.
https://doi.org/10.1111/1346-8138.13933 DOI: https://doi.org/10.1111/1346-8138.13933
Rattananukrom T, Suchonwanit P. Are drug treatment strategies really effective against alopecia areata? Expert Opin Pharmacother 2021; 22: 257-260.
https://doi.org/10.1080/14656566.2020.1854728 DOI: https://doi.org/10.1080/14656566.2020.1854728
Sriphojanart T, Khunkhet S, Suchonwanit P. A retrospective comparative study of the efficacy and safety of two regimens of diphenylcyclopropenone in the treatment of recalcitrant alopecia areata. Dermatol Reports 2017; 9: 7399.
https://doi.org/10.4081/dr.2017.7399 DOI: https://doi.org/10.4081/dr.2017.7399
Done N, Bartolome L, Swallow E, Gao W, Carley C, Wang T, et al. Real-world treatment patterns among patients with alopecia areata in the USA: a retrospective claims analysis. Acta Derm Venereol 2023; 103: adv12445.
https://doi.org/10.2340/actadv.v103.12445 DOI: https://doi.org/10.2340/actadv.v103.12445
Dahabreh D, Jung S, Renert-Yuval Y, Bar J, Del Duca E, Guttman-Yassky E. Alopecia areata: current treatments and new directions. Am J Clin Dermatol 2023; 24: 895-912.
https://doi.org/10.1007/s40257-023-00808-1 DOI: https://doi.org/10.1007/s40257-023-00808-1
King BA, Craiglow BG. Janus kinase inhibitors for alopecia areata. J Am Acad Dermatol 2023; 89: S29-S32.
https://doi.org/10.1016/j.jaad.2023.05.049 DOI: https://doi.org/10.1016/j.jaad.2023.05.049
D'Ovidio R. Alopecia Areata: news on diagnosis, pathogenesis and treatment. G Ital Dermatol Venereol 2014; 149: 25-45.
Messenger AG, Slater DN, Bleehen SS. Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology. Br J Dermatol 1986; 114: 337-347.
https://doi.org/10.1111/j.1365-2133.1986.tb02825.x DOI: https://doi.org/10.1111/j.1365-2133.1986.tb02825.x
Wang EHC, Sallee BN, Tejeda CI, Christiano AM. JAK inhibitors for treatment of alopecia areata. J Invest Dermatol 2018; 138: 1911-1916.
https://doi.org/10.1016/j.jid.2018.05.027 DOI: https://doi.org/10.1016/j.jid.2018.05.027
Lensing M, Jabbari A. An overview of JAK/STAT pathways and JAK inhibition in alopecia areata. Front Immunol 2022; 13: 955035.
https://doi.org/10.3389/fimmu.2022.955035 DOI: https://doi.org/10.3389/fimmu.2022.955035
Kostovic K, Gulin SJ, Mokos ZB, Ceovic R. Tofacitinib, an oral janus kinase inhibitor: perspectives in dermatology. Curr Med Chem 2017; 24: 1158-1167.
https://doi.org/10.2174/1874467210666170113104503 DOI: https://doi.org/10.2174/1874467210666170113104503
Meephansan J, Thummakriengkrai J, Ponnikorn S, Yingmema W, Deenonpoe R, Suchonwanit P. Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction. Arch Dermatol Res 2017; 309: 729-738.
https://doi.org/10.1007/s00403-017-1777-5 DOI: https://doi.org/10.1007/s00403-017-1777-5
Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol 2017; 76: 22-28.
https://doi.org/10.1016/j.jaad.2016.09.007 DOI: https://doi.org/10.1016/j.jaad.2016.09.007
Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. Jci Insight 2016; 1: e89776.
https://doi.org/10.1172/jci.insight.89776 DOI: https://doi.org/10.1172/jci.insight.89776
Jabbari A, Sansaricq F, Cerise J, Chen JC, Bitterman A, Ulerio G, et al. An open-label pilot study to evaluate the efficacy of tofacitinib in moderate to severe patch-type alopecia areata, totalis, and universalis. J Invest Dermatol 2018; 138: 1539-1545.
https://doi.org/10.1016/j.jid.2018.01.032 DOI: https://doi.org/10.1016/j.jid.2018.01.032
Olsen EA, Hordinsky MK, Price VH, Roberts JL, Shapiro J, Canfield D, et al. Alopecia areata investigational assessment guidelines - Part II. National Alopecia Areata Foundation. J Am Acad Dermatol 2004; 51: 440-447.
https://doi.org/10.1016/j.jaad.2003.09.032 DOI: https://doi.org/10.1016/j.jaad.2003.09.032
Paggioli I, Moss J. Alopecia Areata: Case report and review of pathophysiology and treatment with Jak inhibitors. J Autoimmun 2022; 133: 102926.
https://doi.org/10.1016/j.jaut.2022.102926 DOI: https://doi.org/10.1016/j.jaut.2022.102926
Guo L, Feng S, Sun B, Jiang X, Liu Y. Benefit and risk profile of tofacitinib for the treatment of alopecia areata: a systemic review and meta-analysis. J Eur Acad Dermatol Venereol 2020; 34: 192-201.
https://doi.org/10.1111/jdv.15937 DOI: https://doi.org/10.1111/jdv.15937
Ali N, Zirak B, Rodriguez RS, Pauli ML, Truong HA, Lai K, et al. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell 2017; 169: 1119-1129.e11.
https://doi.org/10.1016/j.cell.2017.05.002 DOI: https://doi.org/10.1016/j.cell.2017.05.002
Tembhre MK, Sharma VK. T-helper and regulatory T-cell cytokines in the peripheral blood of patients with active alopecia areata. Br J Dermatol 2013; 169: 543-548.
https://doi.org/10.1111/bjd.12396 DOI: https://doi.org/10.1111/bjd.12396
Moosbrugger-Martinz V, Tripp CH, Clausen BE, Schmuth M, Dubrac S. Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype in mice. J Cell Mol Med 2016; 20: 930-938.
https://doi.org/10.1111/jcmm.12806 DOI: https://doi.org/10.1111/jcmm.12806
Noval Rivas M, Burton OT, Wise P, Charbonnier LM, Georgiev P, Oettgen HC, et al. Regulatory T cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity 2015; 42: 512-523.
https://doi.org/10.1016/j.immuni.2015.02.004 DOI: https://doi.org/10.1016/j.immuni.2015.02.004
Hordinsky M, Kaplan DH. Low-dose interleukin 2 to reverse alopecia areata. JAMA Dermatol 2014; 150: 696-697.
https://doi.org/10.1001/jamadermatol.2014.510 DOI: https://doi.org/10.1001/jamadermatol.2014.510
Le Duff F, Bouaziz JD, Fontas E, Ticchioni M, Viguier M, Dereure O, et al. Low-dose IL-2 for treating moderate to severe alopecia areata: a 52-week multicenter prospective placebo-controlled study assessing its impact on T regulatory cell and NK cell populations. J Invest Dermatol 2021; 141: 933-936.e6.
https://doi.org/10.1016/j.jid.2020.08.015 DOI: https://doi.org/10.1016/j.jid.2020.08.015
Castela E, Le Duff F, Butori C, Ticchioni M, Hofman P, Bahadoran P, et al. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol 2014; 150: 748-751.
https://doi.org/10.1001/jamadermatol.2014.504 DOI: https://doi.org/10.1001/jamadermatol.2014.504
Fukumoto T, Fukumoto R, Magno E, Oka M, Nishigori C, Horita N. Treatments for alopecia areata: a systematic review and network meta-analysis. Dermatol Ther 2021; 34: e14916.
https://doi.org/10.1111/dth.14916 DOI: https://doi.org/10.1111/dth.14916
Zhang W, Li X, Chen B, Zhang J, Torres-Culala KMT, Zhou C. Oral Tofacitinib and systemic corticosteroids, alone or in combination, in patients with moderate-to-severe alopecia areata: a retrospective study. Front Med (Lausanne) 2022; 9: 891434.
https://doi.org/10.3389/fmed.2022.891434 DOI: https://doi.org/10.3389/fmed.2022.891434
Yan D, Fan H, Chen M, Xia L, Wang S, Dong W, et al. The efficacy and safety of JAK inhibitors for alopecia areata: a systematic review and meta-analysis of prospective studies. Front Pharmacol 2022; 13: 950450.
https://doi.org/10.3389/fphar.2022.950450 DOI: https://doi.org/10.3389/fphar.2022.950450
Darwin E, Hirt PA, Fertig R, Doliner B, Delcanto G, Jimenez JJ. Alopecia areata: review of epidemiology, clinical features, pathogenesis, and new treatment options. Int J Trichology 2018; 10: 51-60.
https://doi.org/10.4103/ijt.ijt_99_17 DOI: https://doi.org/10.4103/ijt.ijt_99_17
Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 2012; 32: 23-63.
https://doi.org/10.1615/CritRevImmunol.v32.i1.30 DOI: https://doi.org/10.1615/CritRevImmunol.v32.i1.30
Ramakrishnan V, Akram Husain RS, Ahmed SS. Genetic predisposition of IL-10 promoter polymorphisms with risk of multiple sclerosis: a meta-analysis. J Neuroimmunol 2017; 306: 11-18.
https://doi.org/10.1016/j.jneuroim.2017.02.015 DOI: https://doi.org/10.1016/j.jneuroim.2017.02.015
McElwee KJ, Hoffmann R, Freyschmidt-Paul P, Wenzel E, Kissling S, Sundberg JP, et al. Resistance to alopecia areata in C3H/HeJ mice is associated with increased expression of regulatory cytokines and a failure to recruit CD4+ and CD8+ cells. J Invest Dermatol 2002; 119: 1426-1433.
https://doi.org/10.1046/j.1523-1747.2002.19620.x DOI: https://doi.org/10.1046/j.1523-1747.2002.19620.x
Freyschmidt-Paul P, McElwee KJ, Happle R, Kissling S, Wenzel E, Sundberg JP, et al. Interleukin-10-deficient mice are less susceptible to the induction of alopecia areata. J Invest Dermatol 2002; 119: 980-982.
https://doi.org/10.1046/j.1523-1747.2002.00230.x DOI: https://doi.org/10.1046/j.1523-1747.2002.00230.x
Li J, van Vliet C, Rufaut NW, Jones LN, Sinclair RD, Carbone FR. Laser capture microdissection reveals transcriptional abnormalities in alopecia areata before, during, and after active hair loss. J Invest Dermatol 2016; 136: 715-718.
https://doi.org/10.1016/j.jid.2015.12.003 DOI: https://doi.org/10.1016/j.jid.2015.12.003
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