The Evolving Story of JAK Inhibitors for Treating Alopecia Areata

A Review of Current Progress and Future Directions

Jeff Donovan, MD, FRCPC, PhD

Skin Therapy Letter. 2023;28(3):1-7.

Abstract and Introduction

Abstract

Oral Janus kinase (JAK) inhibitors now have a position as first-line agents for treating advanced alopecia areata. Oral JAK inhibitors are considerably more effective than topical JAK inhibitors, although topical agents may still have a valuable role for specific subgroups of patients. The US FDA approval of baricitinib in 2022 was an important milestone. Numerous JAK inhibitors are now being intensely studied for use in alopecia areata and several additional medications may also become approved in the near future. Accumulating clinical trial data points to a generally good safety profile for JAK inhibitors when used for patients with alopecia areata. However, long-term data pertaining to the safety and efficacy in this patient population are lacking.

Introduction

The treatment of advanced forms of alopecia areata (AA) is more challenging than the milder forms and patients with advanced AA often require systemic therapy in order to regrow hair. Since the introduction of Janus kinase (JAK) inhibitors to the world over a decade ago, these agents have risen to the top of the treatment ladder to become a bona fide first-line therapeutic option for severe AA.^[1] The US FDA approval of baricitinib on June 13, 2022 marked an important new chapter in the field of AA.^[2]

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Table 1. Current JAK inhibitor trials recruiting, in progress or soon to be recruiting (registered at clinicaltrials.gov, accessed January 15, 2023).
Trial Identifier	Molecular or Drug Name	Recruiting	Location	Age Group (in years)
NCT05496426	KL130008 (JAK1/2)	Not yet	China	Adults, 18–65
NCT04006457	Ritlecitinib (JAK3/TEC)	Active, not recruiting	Global	Adult and adolescents, ≥12
NCT04517864	Ritlecitinib (JAK3/TEC)	Active, not recruiting	Global	Adults, 18–50
NCT05470413	Ivarmacitinib SHR0302 (JAK1)	Recruiting	China	Adults, 18–60
NCT05255237	Jaktinib (JAK1/2)	Recruiting	China	Adults, 18- 65
NCT05650333	Ritlecitinib (JAK3/TEC)	Not yet	US	Children, 6–11
NCT05051761	Jaktinib (JAK1/2)	Recruiting	China	Adults, 18–64
NCT05041803	Deuruxolitinib (JAK1/2)	Active, not recruiting	Europe	Adults, 18–65
NCT04784533	Deuruxolitinib (JAK1/2)	Active, not recruiting	US	Adults, 18–65
NCT04445363	Topical Jaktinib (JAK1/2)	Recruiting	China	Adults, 18–65
NCT05398809	Ruxolitinib (JAK1/2)	Recruiting	US	Adult and adolescents, 12–65 (APECED)
NCT04246372	Tofacitinib (JAK1/3)	Recruiting	US	Adult and adolescents, 12–50 (Down syndrome)
NCT03898479	Deuruxolitinib (JAK1/2)	Active, not recruiting	US & Canada	Adults, 18–65
NCT05556265	Deucravacitinib (TYK2)	Not yet	Global	Adults, 18–65

APECED = autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Table 2. List of non-selective and selective JAK inhibitors and use in alopecia areata.
JAK Inhibitor Class	Mechanism of Action (JAK Member Inhibited)	Drug Name	FDA Approved for Use in Humans?	FDA Approved for Alopecia Areata?	Evidence of Benefit in Alopecia Areata?
Non-Selective (first generation)	JAK1/2	Ruxolitinib	Yes	No	Yes
		Baricitinib	Yes	Yes	Yes
		Deuruxolitinib	No	No	Yes
		Jaktinib - oral	No	No	In trials
		Jaktinib - topical	No	No	In trials
		KL130008	No	No	Soon to begin trials
	JAK1/3	Tofacitinib	Yes	No	Yes
		Ifidancitinib	No	No	No
		ATI-501	No	No	Yes (minor benefit)
	JAK1/TYK2	Brepocitinib	No	No	Yes
	JAK1/TYK2	SAR-20347	No	No	Studies not done
	Pan JAK	Peficitinib	No	No	Studies not done
		Oclacitinib	No	No	Studies not done
		Delgocitinib	No	No	No, not as topical
Selective (second generation)	JAK 1 Selective	Filgotinib	Yes	No	Yes, case reports
		Upadacitinib	Yes	No	Yes, case reports
		Solcitinib	No	No	Studies not done
		Abrocitinib	Yes	No	Yes, case reports
		SHR0302	No	No	In trials
		Itacitinib	No	No	Studies not done
		INCV54707	No	No	Studies not done
	JAK3 Selective	Decernotinib	No	No	Studies not done
	JAK3 Selective	Ritlecitinib	No	No	Yes
	TYK2 Selective	Deucravacitinib	Yes	No	Trials to begin
		NDI-031232	No	No	Studies not done
		NDI-031407	No	No	Studies not done

Table 3. Potential contraindications (to be reviewed on case by case basis) to JAK inhibitor use for alopecia areata.
•Prior cancer history • High risk for cancer • Current/past smoking • Age over 65–70 • Prior thromboembolism • High risk for thrombosis • Cardiovascular disease • Active/chronic infections • History of untreated tuberculosis • Pregnancy • Breastfeeding • Low blood counts • Significant renal impairment • Significant hepatic impairment • Prior gastrointestinal perforations • Allergic to JAK inhibitors • Using other systemic immunosuppressive agents • Patient not willing or unable to attend follow-up appointments • Patient not willing or unable to have routine blood tests done • Patient does not understand the current known risks of the drug • Patient does not understand the alternatives to the drug