PRE-JAK INHIBITORS: WHAT WORKS AND WHAT

DOESN’T IN ALOPECIA AREATA

Tiffany Mayo MD, MS, FAADAssistant Professor of Dermatology

University of Alabama at Birmingham

DISCLOSURES

• Clinical Research and Grants to University: Eli Lilly, ChemoCentryx

• Consulting: Janssen• Speaker Board: None

OVERVIEW• Corticosteroids

• Intralesional• Topical• Oral

• Topical Immunotherapy• Diphenylcyclopropenone (DPCP)• Squaric Acid

• Immunosuppressants• Methotrexate• Cyclosporine• Azathioprine

• Adjuvant Therapy• Topical Minoxidil• Anthralin• Topical Calcineurin Inhibitors• Latanoprost/Bimatoprost

Corticosteroids

CORTICOSTEROIDSTopical

• Effective, may consider first line in pediatric patients

• Response rate: ~60%• Clobetasol proprionate

0.05% BID M-F• Consider foam;

ointment --> folliculitis• Re-evaluate at 3

months

Oral

• Effective but side effect profile unfavorable

• Response rate: ~60%• High relapse rate with

daily administration• Pulse Therapy =

similar results, less relapse, less, side effects

• Treatment: 40 - 60mg tapered over 6 weeks

Intralesional

• First-line therapy for AA affecting <50% scalp

• Response rate: >60%• Dose:

• Scalp: 5mg/mL• Brows: 2.5mg/mL

• Treatment frequency: q4-6 weeks

• Discontinue after 3-6 months if no improvement

CORTICOSTEROIDSTopical

• Effective, may consider first line in pediatric patients

• Response rate: ~60%• Clobetasol proprionate

0.05% BID M-F• Consider foam;

ointment --> folliculitis• Re-evaluate at 3

months

Oral

• Effective but side effect profile unfavorable

• Response rate: ~60%• High relapse rate with

daily administration• Pulse Therapy =

similar results, less relapse, less, side effects

• Treatment: 40 - 60mg tapered over 6 weeks

Intralesional

• First line therapy for AA affecting <50% scalp

• Response rate: >60%• Dose:

• Scalp: 5mg/mL• Brows: 2.5mg/mL

• Treatment frequency: q4-6 weeks

• Discontinue after 3-6 months if no improvement

EFFICACY OF ILK AND TOPICAL STEROIDS

T.W. Chu, M. AlJasser, A. Alharbi, O. Abahussein, K. McElwee, J. Shapiro Benefit of different concentrations of intralesionaltriamcinolone acetonide in alopecia areata: an intrasubject pilot study. J Am Acad Dermatol, 73 (2015), pp. 338-340

Tosti, A., et al. "Clobetasol Propionate 0.05% Under Occlusion in the Treatment of Alopecia totalis/universalis." Journal of the American Academy of Dermatology, vol. 49, no. 1, 2003, pp. 96-98.

Topical Immunotherapy

DPCP/SQUARIC ACID

• Appropriate for patients with > 50% involvement

• Response rate: 50-70% • Patient is initially sensitized and treated once

weekly for 1 year• Response time: 3 months• Taper dose upon discontinuation to prevent

relapse

Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031. Review. PubMed PMID: 20115946.

DPCP/SQUARIC ACID

• Appropriate for patients with > 50% involvement

• Response rate: 50-70% • Patient is initially sensitized and treated once

weekly for 1 year• Response time: 3 months• Taper dose upon discontinuation to prevent

relapse

Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031. Review. PubMed PMID: 20115946.

Immunosuppressants

IMMUNOSUPPRESSANTSCyclosporine

• Response: ~ 30%• Dose: 4mg/kg/day• Improved response in

combination with corticosteroids

• Response time: 3 mo• Not generally

recommended due to adverse side effect profile, high relapse rate

Azathioprine

• Response: ~ 40 - 50%• Dose: 2mg/kg/day• Response time: 4mo• Adverse effects

in 20%• Major consideration:

risk of myelosuppression

Methotrexate

• Response rate: ~ 60%• Dose: 15 - 25mg/

week• Improved response in

combination with corticosteroids

• Response time: 3-4 mo• Adults > Pediatric• Major Considerations:

hepatic impairment, childbearing status

IMMUNOSUPPRESSANTSCyclosporine

• Response: ~ 30%• Dose: 4mg/kg/day• Improved response in

combination with corticosteroids,

• Response time: 3mo• Not generally

recommended due to adverse side effect profile, high relapse rate

Azathioprine

• Response: ~ 40 - 50%• Dose: 2mg/kg/day• Response time: 4mo• Adverse effects

in 20%• Major consideration:

risk of myelosuppression

Methotrexate

• Response rate: ~ 60%• Dose: 15 - 25mg/

week• Improved response in

combination with corticosteroids

• Response time: 3-4 mo• Adults > Pediatric• Major Considerations:

hepatic impairment, childbearing status

Adjuvant Therapy

Latanoprost

• Response. rate: 0-25%

• Several reports show lack of efficacy

Tacrolimus

• Response rate: ~ <5%

Anthralin

• Response rate: ~ 25-75%

• Second line agent in pediatric AA

• Apply 0.5% or 1% up to 30 min daily. Titrate to achieve dermatitis

Minoxidil

• Response rate: ~ 25-80%

• Frequently used with topical steroids

Latanoprost

• Response. rate: 0-25%

• Several reports show lack of efficacy

Tacrolimus

• Response rate: ~ <5%

Anthralin

• Response rate: ~ 25-75%

• Second line agent in pediatric AA

• Apply 0.5% or 1% up to 30 min daily. Titrate to achieve dermatitis

Minoxidil

• Response rate: ~ 25-80%

• Frequently used with topical steroids

CONCLUSIONSWhat Doesn’t

• Topical Tacrolimus/ Pimecrolimus

• Latanoprost/ Bimatoprost

Consider with Caution

• Oral corticosteroids• Cyclosporine• Azathioprine

What Works

• ILK• Topical Steroids• Methotrexate• Atralin• Minoxidil

REFERENCESCorticosteroids

• Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031. Review. PubMed PMID: 20115946.

• Chu TW, AlJasser M, Alharbi A, Abahussein O, McElwee K, Shapiro J. Benefit of different concentrations of intralesional triamcinolone acetonide in alopecia areata: An intrasubject pilot study. J Am Acad Dermatol. 2015 Aug;73(2):338-40. doi: 10.1016/j.jaad.2015.04.049. PubMed PMID: 26183987.

• Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, Shapiro J. Alopecia areata: An appraisal of new treatment approaches and overview of current therapies. J Am Acad Dermatol. 2018 Jan;78(1):15-24. doi:10.1016/j.jaad.2017.04.1142. Review. PubMed PMID: 29241773.

• Friedli A, Labarthe MP, Engelhardt E, Feldmann R, Salomon D, Saurat JH. Pulse methylprednisolone therapy for severe alopecia areata: an open prospective study of 45 patients. J Am Acad Dermatol. 1998 Oct;39(4 Pt 1):597-602.

• Kurosawa M, Nakagawa S, Mizuashi M, Sasaki Y, Kawamura M, Saito M, Aiba S. A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata. Dermatology. 2006;212(4):361-5.

• Lai VWY, Chen G, Gin D, Sinclair R. Systemic treatments for alopecia areata: A systematic review. Australas J Dermatol. 2019 Feb;60(1):e1-e13. doi:10.1111/ajd.12913. Epub 2018 Sep 6. PubMed PMID: 30191561.

Immunotherapy

• Rokhsar CK, Shupack JL, Vafai JJ, Washenik K. Efficacy of topical sensitizers in the treatment of alopecia areata. J Am Acad Dermatol. 1998 Nov;39(5 Pt 1):751-61. Review.

• Ohlmeier MC, Traupe H, Luger TA, Böhm M. Topical immunotherapy with diphenylcyclopropenone of patients with alopecia areata--a large retrospective study on 142 patients with a self-controlled design. J Eur Acad Dermatol Venereol. 2012 Apr;26(4):503-7.

Immunosuppressants

• Phan K, Ramachandran V, Sebaratnam DF. Methotrexate for alopecia areata: A systematic review and meta-analysis. J Am Acad Dermatol. 2019 Jan;80(1):120-127.e2. doi: 10.1016/j.jaad.2018.06.064. Epub 2018 Jul 10. PubMed PMID: 30003990.

• Anuset D, Perceau G, Bernard P, Reguiai Z. Efficacy and Safety of Methotrexate Combined with Low- to Moderate-Dose Corticosteroids for Severe Alopecia Areata. Dermatology. 2016;232(2):242-8. doi: 10.1159/000441250. Epub 2016 Jan 7. PubMed PMID: 26735937.

• Lai VWY, Chen G, Gin D, Sinclair R. Cyclosporine for moderate-to-severe alopecia areata: A double-blind, randomized, placebo-controlled clinical trial of efficacy and safety. J Am Acad Dermatol. 2019 Sep;81(3):694-701. doi:10.1016/j.jaad.2019.04.053. Epub 2019 Apr 30. PubMed PMID: 31048013.

• Vañó-Galván S, Hermosa-Gelbard Á, Sánchez-Neila N, Miguel-Gómez L, Saceda-Corralo D, Rodrigues-Barata R, Jaén P. Treatment of recalcitrant adult alopecia areata universalis with oral azathioprine. J Am Acad Dermatol. 2016 May;74(5):1007-8. doi: 10.1016/j.jaad.2015.12.055. PubMed PMID: 27085230.

• Farshi S, Mansouri P, Safar F, Khiabanloo SR. Could azathioprine be considered as a therapeutic alternative in the treatment of alopecia areata? A pilot study. Int J Dermatol. 2010 Oct;49(10):1188-93. doi: 10.1111/j.1365-4632.2010.04576.x. PubMed PMID: 20883409.

Adjuvant Therapies

• Price VH, WilleyChoi YM, Diehl J, Levins PC. Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes. J Am Acad Dermatol. 2015 Apr;72(4):712-6. doi: 10.1016/j.jaad.2014.10.012. Epub 2015 Jan 16. Review. PubMed PMID: 25601618.

• A, Chen BK. Topical tacrolimus in alopecia areata. J Am Acad Dermatol. 2005 Jan;52(1):138-9. PubMed PMID: 15627095.

• Olsen EA, Carson SC, Turney EA. Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata. Arch Dermatol. 1992 Nov;128(11):1467-73. PubMed PMID: 1444500.

• Wu SZ, Wang S, Ratnaparkhi R, Bergfeld WF. Treatment of pediatric alopecia areata with anthralin: A retrospective study of 37 patients. Pediatr Dermatol. 2018 Nov;35(6):817-820. doi: 10.1111/pde.13703. Epub 2018 Oct 18. PubMed PMID:30338548.

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