Comparative Efficacy and Safety of Janus Kinase Inhibitors Used in Alopecia Areata: A Systematic Review and Meta-analysis
DOI:
https://doi.org/10.2340/actadv.v103.4536Keywords:
alopecia areata, polygenic autoimmune disease, JAK inhibitors, biologicalAbstract
The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.
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Solimani F, Meier K, Ghoreschi K. Emerging topical and systemic JAK inhibitors in dermatology. Front Immunol 2019; 10: 2847.
https://doi.org/10.3389/fimmu.2019.02847 DOI: https://doi.org/10.3389/fimmu.2019.02847
Uzuncakmak TK, Engin B, Serdaroglu S, Tuzun Y. Demographic and clinical features of 1,641 patients with alopecia areata, alopecia totalis, and alopecia universalis: a single-center retrospective study. Skin Appendage Disord 2021; 7: 8-12.
https://doi.org/10.1159/000510880 DOI: https://doi.org/10.1159/000510880
Yang S, Yang J, Liu JB, Wang HY, Yang Q, Gao M, et al. The genetic epidemiology of alopecia areata in China. Br J Dermatol 2004; 151: 16-23.
https://doi.org/10.1111/j.1365-2133.2004.05915.x DOI: https://doi.org/10.1111/j.1365-2133.2004.05915.x
Guzmán-Sánchez DA, Villanueva-Quintero GD, Alfaro Alfaro N, McMichael A. A clinical study of alopecia areata in Mexico. Int J Dermatol 2007; 46: 1308-1310.
https://doi.org/10.1111/j.1365-4632.2007.03320.x DOI: https://doi.org/10.1111/j.1365-4632.2007.03320.x
Mirzoyev SA, Schrum AG, Davis MDP, Torgerson RR. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990-2009. J Invest Dermatol 2014; 134: 1141-1142.
https://doi.org/10.1038/jid.2013.464 DOI: https://doi.org/10.1038/jid.2013.464
Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol 2015; 24: 397-403.
https://doi.org/10.2147/CCID.S53985 DOI: https://doi.org/10.2147/CCID.S53985
Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med 2012; 366: 1515-1525.
https://doi.org/10.1056/NEJMra1103442 DOI: https://doi.org/10.1056/NEJMra1103442
Johnson R, Roh E, Saavedra A, Wolff K. Fitzpatrick's colour atlas and synopsis of clinical dermatology. 8th edn. New York: McGrawHill Edu; 2017.
Rodriguez TA, Fernandes KE, Dresser KL, Duvic M. National Alopecia Areata Registry. Concordance rate of alopecia areata in identical twins supports both genetic and environmental factors. J Am Acad Dermatol 2010; 62: 525-527.
https://doi.org/10.1016/j.jaad.2009.02.006 DOI: https://doi.org/10.1016/j.jaad.2009.02.006
Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol 2010; 62: 191-202.
https://doi.org/10.1016/j.jaad.2009.10.031 DOI: https://doi.org/10.1016/j.jaad.2009.10.031
Trüeb RM, Dutra H, Dias MFRG. A comment on JAK inhibitors for treatment of alopecia areata. Int J Trichology 2018; 10: 193-197.
https://doi.org/10.4103/ijt.ijt_62_18 DOI: https://doi.org/10.4103/ijt.ijt_62_18
Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: an appraisal of new treatment approaches and overview of current therapies. J Am Acad Dermatol 2018; 78: 15-24.
https://doi.org/10.1016/j.jaad.2017.04.1142 DOI: https://doi.org/10.1016/j.jaad.2017.04.1142
Zheng C, Tosti A. Alopecia areata: new treatment options including Janus kinase inhibitors. Dermatol Clin 2021; 39: 407-415.
https://doi.org/10.1016/j.det.2021.03.005 DOI: https://doi.org/10.1016/j.det.2021.03.005
Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 2014; 20: 1043-1049.
https://doi.org/10.1038/nm.3645 DOI: https://doi.org/10.1038/nm.3645
Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, et al. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv 2015; 1: e1500973.
https://doi.org/10.1126/sciadv.1500973 DOI: https://doi.org/10.1126/sciadv.1500973
Triyangkulsri K, Suchonwanit P. Role of janus kinase inhibitors in the treatment of alopecia areata. Drug Des Devel Ther 2018; 27: 2323-2335.
https://doi.org/10.2147/DDDT.S172638 DOI: https://doi.org/10.2147/DDDT.S172638
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009; 151: W65-W94.
https://doi.org/10.7326/0003-4819-151-4-200908180-00136 DOI: https://doi.org/10.7326/0003-4819-151-4-200908180-00136
Benton S, Farah R, Freese R, Hordinsky M. Tofacitinib as a pragmatic treatment choice for alopecia areata: a retrospective review. Dermatol Ther 2022; 35: e15310.
https://doi.org/10.1111/dth.15310 DOI: https://doi.org/10.1111/dth.15310
King B, Mesinkovska N, Mirmirani P, Bruce S, Kempers S, Guttman-Yassky E, et al. Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata. J Am Acad Dermatol 2022; 87: 306-313.
https://doi.org/10.1016/j.jaad.2022.03.045 DOI: https://doi.org/10.1016/j.jaad.2022.03.045
King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med 2022; 386: 1687-1699.
https://doi.org/10.1056/NEJMoa2110343 DOI: https://doi.org/10.1056/NEJMoa2110343
Mikhaylov D, Glickman JW, Del Duca E, Nia J, Hashim P, Singer GK, et al. A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata. Arch Dermatol Res 2022; Mar 1. [Online ahead of print]
https://doi.org/10.1007/s00403-022-02336-0 DOI: https://doi.org/10.1007/s00403-022-02336-0
Guttman-Yassky E, Pavel AB, Diaz A, Zhang N, Del Duca E, Estrada Y, et al. Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers. J Allergy Clin Immunol 2022; 149: 1318-1328.
https://doi.org/10.1016/j.jaci.2021.10.036 DOI: https://doi.org/10.1016/j.jaci.2021.10.036
Esteves M, Lopes S, Azevedo F, Pedrosa A. Effectiveness of oral tofacitinib dose tapering in a case of alopecia areata universalis. Skin Appendage Disord 2021; 7: 36-40.
https://doi.org/10.1159/000510673 DOI: https://doi.org/10.1159/000510673
Jerjen R, Meah N, Trindade de Carvalho L, Wall D, Eisman S, Sinclair R, et al. Treatment of alopecia areata in pre-adolescent children with oral tofacitinib: A retrospective study. Pediatr Dermatol 2021; 38: 103-108.
https://doi.org/10.1111/pde.14422 DOI: https://doi.org/10.1111/pde.14422
Lai VWY, Bokhari L, Sinclair R. Sublingual tofacitinib for alopecia areata: a roll-over pilot clinical trial and analysis of pharmacokinetics. Int J Dermatol 2021; 60: 1135-1139.
https://doi.org/10.1111/ijd.15657 DOI: https://doi.org/10.1111/ijd.15657
King B, Guttman-Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, et al. A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. J Am Acad Dermatol 2021; 85: 379-387.
https://doi.org/10.1016/j.jaad.2021.03.050 DOI: https://doi.org/10.1016/j.jaad.2021.03.050
King B, Ko J, Forman S, Ohyama M, Mesinkovska N, Yu G, et al. Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: phase 2 results from a randomized controlled study. J Am Acad Dermatol 2021; 85: 847-853.
https://doi.org/10.1016/j.jaad.2021.05.050 DOI: https://doi.org/10.1016/j.jaad.2021.05.050
Dincer Rota D, Emeksiz MAC, Erdogan FG, Yildirim D. Experience with oral tofacitinib in severe alopecia areata with different clinical responses. J Cosmet Dermatol 2021; 20: 3026-3033.
https://doi.org/10.1111/jocd.13966 DOI: https://doi.org/10.1111/jocd.13966
Wambier CG, Craiglow BG, King BA. Combination tofacitinib and oral minoxidil treatment for severe alopecia areata. J Am Acad Dermatol 2021; 85: 743-745.
https://doi.org/10.1016/j.jaad.2019.08.080 DOI: https://doi.org/10.1016/j.jaad.2019.08.080
Kerkemeyer KLS, John JM, Sinclair R, Bhoyrul B. Response of alopecia areata of the beard to oral tofacitinib. J Am Acad Dermatol 2020; 82: 1228-1230.
https://doi.org/10.1016/j.jaad.2019.10.058 DOI: https://doi.org/10.1016/j.jaad.2019.10.058
Yale K, Pourang A, Plikus MV, Mesinkovska NA. At the crossroads of 2 alopecias: androgenetic alopecia pattern of hair regrowth in patients with alopecia areata treated with oral Janus kinase inhibitors. JAAD Case Rep 2020; 6: 444-446.
https://doi.org/10.1016/j.jdcr.2020.02.026 DOI: https://doi.org/10.1016/j.jdcr.2020.02.026
Akdogan N, Ersoy-Evans S, Doğan S, Atakan N. Experience with oral tofacitinib in two adolescents and seven adults with alopecia areata. Dermatol Ther 2019; 32: e13118.
https://doi.org/10.1111/dth.13118 DOI: https://doi.org/10.1111/dth.13118
Almutairi N, Nour TM, Hussain NH. Janus kinase inhibitors for the treatment of severe alopecia areata: an open-label comparative study. Dermatology 2019; 235: 130-136.
https://doi.org/10.1159/000494613 DOI: https://doi.org/10.1159/000494613
Chen YY, Lin SY, Chen YC, Yang CC, Lan CE. Low-dose tofacitinib for treating patients with severe alopecia areata: an efficient and cost-saving regimen. Eur J Dermatol 2019; 29: 667-669.
https://doi.org/10.1684/ejd.2019.3668 DOI: https://doi.org/10.1684/ejd.2019.3668
Craiglow BG, King BA. Tofacitinib for the treatment of alopecia areata in preadolescent children. J Am Acad Dermatol 2019; 80: 568-570.
https://doi.org/10.1016/j.jaad.2018.08.041 DOI: https://doi.org/10.1016/j.jaad.2018.08.041
Dai YX, Chen CC. Tofacitinib therapy for children with severe alopecia areata. J Am Acad Dermatol 2019; 80: 1164-1166.
https://doi.org/10.1016/j.jaad.2018.12.041 DOI: https://doi.org/10.1016/j.jaad.2018.12.041
Liu LY, King BA. Ruxolitinib for the treatment of severe alopecia areata. J Am Acad Dermatol 2019; 80: 566-568.
https://doi.org/10.1016/j.jaad.2018.08.040 DOI: https://doi.org/10.1016/j.jaad.2018.08.040
Serdaroğlu S, Engin B, Çelik U, Erkan E, Aşkın Ö, Oba Ç, et al. Clinical experiences on alopecia areata treatment with tofacitinib: a study of 63 patients. Dermatol Ther 2019; 32: e12844.
https://doi.org/10.1111/dth.12844 DOI: https://doi.org/10.1111/dth.12844
Shin JW, Huh CH, Kim MW, Lee JS, Kwon O, Cho S, et al. Comparison of the treatment outcome of oral tofacitinib with other conventional therapies in refractory alopecia totalis and universalis: a retrospective study. Acta Derm Venereol 2019; 99: 41-46.
https://doi.org/10.2340/00015555-3057 DOI: https://doi.org/10.2340/00015555-3057
Shivanna CB, Shenoy C, Priya RA. Tofacitinib (selective janus kinase inhibitor 1 and 3): a promising therapy for the treatment of alopecia areata: a case report of six patients. Int J Trichology 2018; 10: 103-107.
https://doi.org/10.4103/ijt.ijt_21_18 DOI: https://doi.org/10.4103/ijt.ijt_21_18
Cheng MW, Kehl A, Worswick S, Goh C. Successful treatment of severe alopecia areata with oral or topical tofacitinib. J Drugs Dermatol 2018; 17: 800-803.
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
Lee JS, Huh CH, Kwon O, Yoon HS, Cho S, Park HS. Nail involvement in patients with moderate-to-severe alopecia areata treated with oral tofacitinib. J Dermatolog Treat 2018; 29: 819-822.
https://doi.org/10.1080/09546634.2018.1466024 DOI: https://doi.org/10.1080/09546634.2018.1466024
Liu LY, Craiglow BG, King BA. Tofacitinib 2% ointment, a topical Janus kinase inhibitor, for the treatment of alopecia areata: a pilot study of 10 patients. J Am Acad Dermatol 2018; 78: 403-404.
https://doi.org/10.1016/j.jaad.2017.10.043 DOI: https://doi.org/10.1016/j.jaad.2017.10.043
Patel NU, Oussedik E, Grammenos A, Pichardo-Geisinger R. A Case report highlighting the effective treatment of alopecia universalis with tofacitinib in an adolescent and adult patient. J Cutan Med Surg 2018; 22: 439-442.
https://doi.org/10.1177/1203475418760512 DOI: https://doi.org/10.1177/1203475418760512
Putterman E, Castelo-Soccio L. Topical 2% tofacitinib for children with alopecia areata, alopecia totalis, and alopecia universalis. J Am Acad Dermatol 2018; 78: 1207-1209.
https://doi.org/10.1016/j.jaad.2018.02.031 DOI: https://doi.org/10.1016/j.jaad.2018.02.031
Castelo-Soccio L. Experience with oral tofacitinib in 8 adolescent patients with alopecia universalis. J Am Acad Dermatol 2017; 76: 754-755.
https://doi.org/10.1016/j.jaad.2016.11.038 DOI: https://doi.org/10.1016/j.jaad.2016.11.038
Deeb M, Beach RA. A case of topical ruxolitinib treatment failure in alopecia areata. J Cutan Med Surg 2017; 21: 562-563.
https://doi.org/10.1177/1203475417716363 DOI: https://doi.org/10.1177/1203475417716363
Erduran F, Adışen E, Aksakal AB. Excellent response to tofacitinib treatment in a patient with alopecia universalis. Acta Dermatovenerol Alp Pannonica Adriat 2017; 26: 47-49.
https://doi.org/10.15570/actaapa.2017.15 DOI: https://doi.org/10.15570/actaapa.2017.15
Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of alopecia areata with tofacitinib. JAMA Dermatol 2017; 153: 600-602.
https://doi.org/10.1001/jamadermatol.2017.0001 DOI: https://doi.org/10.1001/jamadermatol.2017.0001
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
Park HS, Kim MW, Lee JS, Yoon HS, Huh CH, Kwon O, et al. Oral tofacitinib monotherapy in Korean patients with refractory moderate-to-severe alopecia areata: a case series. J Am Acad Dermatol 2017; 77: 978-980.
https://doi.org/10.1016/j.jaad.2017.06.027 DOI: https://doi.org/10.1016/j.jaad.2017.06.027
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
Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 2016; 1: e89790.
https://doi.org/10.1172/jci.insight.89790 DOI: https://doi.org/10.1172/jci.insight.89790
Phan K, Sebaratnam DF. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2019; 33: 850-856.
https://doi.org/10.1111/jdv.15489 DOI: https://doi.org/10.1111/jdv.15489
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
Ho Lee Y, Gyu Song G. Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis. J Clin Pharm Ther 2020; 45: 674-681.
https://doi.org/10.1111/jcpt.13142 DOI: https://doi.org/10.1111/jcpt.13142
Guidelli GM, Viapiana O, Luciano N, De Santis M, Boffini N, Quartuccio L, et al. Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study. Clin Exp Rheumatol 2021; 39: 868-873.
https://doi.org/10.55563/clinexprheumatol/pudtpo DOI: https://doi.org/10.55563/clinexprheumatol/pudtpo
Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis 2016; 75: 831-841.
https://doi.org/10.1136/annrheumdis-2014-205847 DOI: https://doi.org/10.1136/annrheumdis-2014-205847
Genovese MC, Kremer JM, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib, an oral Janus Kinase (JAK)1/JAK2 inhibitor, in patients with active rheumatoid arthritis (RA) and an inadequate response to TNF inhibitors: results of the phase 3 RA-beacon study. Ann Rheum Dis 2015; 74: 753-776.
https://doi.org/10.1136/annrheumdis-2015-eular.1427 DOI: https://doi.org/10.1136/annrheumdis-2015-eular.1427
Winthrop KL, Park SH, Gul A, Cardiel MH, Gomez-Reino JJ, Tanaka Y, et al. Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis. Ann Rheum Dis 2016; 75: 1133-1138.
https://doi.org/10.1136/annrheumdis-2015-207319 DOI: https://doi.org/10.1136/annrheumdis-2015-207319
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