Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.
Humans
Pyrimidines
/ administration & dosage
Piperidines
/ administration & dosage
Male
Alopecia Areata
/ drug therapy
Double-Blind Method
Female
Azathioprine
/ administration & dosage
Adolescent
Adult
Young Adult
Alopecia
/ drug therapy
Treatment Outcome
Protein Kinase Inhibitors
/ adverse effects
Administration, Oral
Child
Pyrroles
/ administration & dosage
Severity of Illness Index
Immunosuppressive Agents
/ adverse effects
Alopecia Areata
Azathioprine
Immune suppression
JAK inhibitor
Tofacitinib
Journal
Archives of dermatological research
ISSN: 1432-069X
Titre abrégé: Arch Dermatol Res
Pays: Germany
ID NLM: 8000462
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
29
04
2024
accepted:
23
06
2024
revised:
21
06
2024
medline:
5
7
2024
pubmed:
5
7
2024
entrez:
5
7
2024
Statut:
epublish
Résumé
Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.
Sections du résumé
BACKGROUND
BACKGROUND
Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair.
OBJECTIVE
OBJECTIVE
To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants.
METHODS
METHODS
In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study.
RESULTS
RESULTS
A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed.
CONCLUSIONS
CONCLUSIONS
Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.
Identifiants
pubmed: 38967866
doi: 10.1007/s00403-024-03203-w
pii: 10.1007/s00403-024-03203-w
doi:
Substances chimiques
tofacitinib
87LA6FU830
Pyrimidines
0
Piperidines
0
Azathioprine
MRK240IY2L
Protein Kinase Inhibitors
0
Pyrroles
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Randomized Controlled Trial
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
458Subventions
Organisme : Hiranis Pharmaceuticals, Karachi, Pakistan
ID : NA
Organisme : Hiranis Pharmaceuticals, Karachi, Pakistan
ID : NA
Organisme : Sihat Sahulat Program, Pakistan
ID : NA
Organisme : Sihat Sahulat Program, Pakistan
ID : NA
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Pratt CH, King LE, Messenger AG et al (2017) Alopecia Areata. Nat Reviews Disease Primers 3:17011
doi: 10.1038/nrdp.2017.11
pubmed: 28300084
Liu LY, King BA, Craiglow BG (2016) Health-related quality of life (HRQoL) among patients with alopecia areata (AA): a systematic review. J Am Acad Dermatol 75(4):806–812e3
doi: 10.1016/j.jaad.2016.04.035
pubmed: 27436156
Liu LY, King BA, Craiglow BG (2018) Alopecia Areata is associated with impaired health-related quality of life: a survey of affected adults and children and their families. J Am Acad Dermatol 79(3):556–558e1
doi: 10.1016/j.jaad.2018.01.048
pubmed: 29425723
Aldhouse NVJ, Kitchen H, Knight S et al (2020) You lose your hair, what’s the big deal?’ I was so embarrassed, I was so self-conscious, I was so depressed: a qualitative interview study to understand the psychosocial burden of Alopecia Areata. J Patient-Reported Outcomes 4:76
doi: 10.1186/s41687-020-00240-7
Petukhova L, Duvic M, Hordinsky M et al (2010) Genome-wide association study in Alopecia Areata implicates both innate and adaptive immunity. Nature 466(7302):113–117
doi: 10.1038/nature09114
pubmed: 20596022
pmcid: 2921172
Gilhar A, Paus R, Kalish RS (2007) Lymphocytes, neuropeptides, and genes involved in Alopecia Areata. J Clin Invest 117(8):2019–2027
doi: 10.1172/JCI31942
pubmed: 17671634
pmcid: 1934574
Xing L, Dai Z, Jabbari A et al (2014) Alopecia Areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20(9):1043–1049
doi: 10.1038/nm.3645
pubmed: 25129481
pmcid: 4362521
de Oliveira AB, Alpalhão M, Filipe P, Maia-Silva J (2019) The role of Janus kinase inhibitors in the treatment of Alopecia Areata: a systematic review. Dermatol Ther 32(5):e13053
doi: 10.1111/dth.13053
pubmed: 31381252
Damsky W, King BA (2017) JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol 76(4):736–744
doi: 10.1016/j.jaad.2016.12.005
pubmed: 28139263
pmcid: 6035868
King B, Guttman-Yassky E, Peeva E et al (2021) 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 85(2):379–387
doi: 10.1016/j.jaad.2021.03.050
pubmed: 33757798
European Medicines Agency (2022) Summary of product characteristics: Olumiant (baricitinib) film-coated tablets. http://www.ema.europa.eu/
(2023) Eli Lilly and Company. OLUMIANT (baricitinib): US prescribing information. http://pi.lilly.com/us/zyprexa-pi.pdf . (2023)Accessed: November 2023
(2023) LITFULO™ (ritlecitinib) capsules, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215830s000lbl.pdf . (2023)Accessed
Blair HA (2023) Ritlecitinib: first approval. Drugs 1315–1321
Mease PJ, Orbai AM, FitzGerald O et al (2023) Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies. Arthritis Res Therapy 25:153
doi: 10.1186/s13075-023-03108-5
Traynor K (2012) FDA approves tofacitinib for rheumatoid arthritis. Am J Health-System Pharm 69(24):2120
Sandborn WJ, Su C, Sands BE et al (2017) Tofacitinib as induction and maintenance therapy for Ulcerative Colitis. N Engl J Med 376(18):1723–1736
doi: 10.1056/NEJMoa1606910
pubmed: 28467869
Deodhar A, Sliwinska-Stanczyk P, Xu H et al (2021) Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis 80(8):1004–1013
doi: 10.1136/annrheumdis-2020-219601
pubmed: 33906853
Ruperto N, Brunner HI, Synoverska O et al (2021) Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet 398(10315):1984–1996
doi: 10.1016/S0140-6736(21)01255-1
pubmed: 34767764
Craiglow BG, King BA (2014) Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatology 134(12):2988–2990
doi: 10.1038/jid.2014.260
Almutairi N, Nour TM, Hussain NH (2019) Janus kinase inhibitors for the treatment of severe Alopecia Areata: an open-label comparative study. Dermatology 235(2):130–136
doi: 10.1159/000494613
pubmed: 30566941
Liu LY, Craiglow BG, Dai F, King BA (2017) Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol 76(1):22–28
doi: 10.1016/j.jaad.2016.09.007
pubmed: 27816293
Crispin MK, Ko JM, Craiglow BG et al (2016) Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with Alopecia Areata. JCI Insight 1(15):e89776
Enzan N, Kitadate A, Yoshioka M et al (2019) Cutaneous involvement of diffuse large B-cell lymphoma incidentally diagnosed based on random skin biopsy of normal-appearing skin. Eur J Dermatology 29(6):666–667
doi: 10.1684/ejd.2019.3667
Zhang W, Li X, Chen B et al (2022) Oral Tofacitinib and systemic corticosteroids, alone or in combination, in patients with moderate-to-severe Alopecia Areata: a retrospective study. Front Med 9:891434
doi: 10.3389/fmed.2022.891434
Shin JW, Huh CH, Kim MW et al (2018) Comparison of the treatment outcome of oral tofacitinib with other conventional therapies in refractory alopecia totalis and universalis: a retrospective study. Acta Dermato-Venereologica 99(1):41–46
Hogan S, Wang S, Ibrahim O et al (2019) Long-term treatment with tofacitinib in severe alopecia areata: an update. J Clin Aesthetic Dermatology 12(6):12–14
Kerkemeyer KLS, John JM, Sinclair R, Bhoyrul B (2020) Response of Alopecia Areata of the beard to oral tofacitinib. J Am Acad Dermatol 82(5):1228–1230
doi: 10.1016/j.jaad.2019.10.058
pubmed: 31678329
Park HS, Kim MW, Lee JS et al (2017) Oral tofacitinib monotherapy in Korean patients with refractory moderate-to-severe Alopecia Areata: a case series. J Am Acad Dermatol 77(5):978–980
doi: 10.1016/j.jaad.2017.06.027
pubmed: 29029911
Jabbari A, Sansaricq F, Cerise J et al (2018) An open-label pilot study to evaluate the efficacy of Tofacitinib in moderate to severe Patch-Type Alopecia Areata, Totalis, and Universalis. J Invest Dermatology 138(7):1539–1545
doi: 10.1016/j.jid.2018.01.032
Sidbury R, Davis DM, Cohen DE et al (2014) Guidelines of care for the management of atopic dermatitis: Sect. 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 71(2):327–349
doi: 10.1016/j.jaad.2014.03.030
pubmed: 24813298
pmcid: 4410179
Schram ME, Borgonjen RJ, Cathelijne; et al (1950) Off-label use of azathioprine in Dermatology a systematic review. Archives Dermatology Dermatol 147(4):474–488
doi: 10.1001/archdermatol.2011.79
Anstey AV, Wakelin S, Reynolds NJ (2004) Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 151(6):1123–1132
doi: 10.1111/j.1365-2133.2004.06323.x
pubmed: 15606506
Shapiro J, Canfield D, Duvic M et al (2004) Alopecia Areata investigational assessment guidelines e part II. J Am Acad Dermatol 51(3):440–447
doi: 10.1016/j.jaad.2003.09.032
pubmed: 15337988
Ibrahim O, Bayart CB, Hogan S et al (2017) Treatment of Alopecia Areata with tofacitinib. JAMA Dermatology 153(6):600–602
doi: 10.1001/jamadermatol.2017.0001
pubmed: 28355451
pmcid: 5817614
Shaikh HA, Ur Rehman F, Kiayani AJ (2019) Efficacy and safety of azathioprine in Alopecia Areata. J Pakistan Association Dermatologists 29(2):215–219
Hordinsky M, Hebert AA, Gooderham M et al (2023) Efficacy and safety of ritlecitinib in adolescents with Alopecia Areata: results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial. Pediatr Dermatol 1–7. https://doi.org/10.1111/pde.15378
Craiglow BG, Liu LY, King BA (2017) Tofacitinib for the treatment of Alopecia Areata and variants in adolescents. J Am Acad Dermatol 76(1):29–32
doi: 10.1016/j.jaad.2016.09.006
pubmed: 27816292
Cua VCS, Villena JPDS, Lizarondo FPJ, Yap-Silva C (2019) Azathiopine for the treatment of extensive forms of Alopecia Areata: a systematic review. Acta Med Philippina 53(2):132–141
Farshi S, Mansouri P, Safar F, Khiabanloo SR (2010) Could azathioprine be considered as a therapeutic alternative in the treatment of Alopecia Areata? A pilot study. Int J Dermatol 49(10):1188–1193
doi: 10.1111/j.1365-4632.2010.04576.x
pubmed: 20883409