Janus Kinase and Tyrosine Kinase Inhibitors in Dermatology

Conclusion

Many inflammatory cytokines involved in the pathogenesis of skin disorders signal via the JAK-STAT pathway. Thus, this drug class has the potential for broad therapeutic utility within dermatology. Currently, JAK inhibitors are only FDA approved for dermatologic, rheumatologic, and hematologic conditions. Recent studies show the utility of JAK inhibitors in treating atopic dermatitis, psoriasis, psoriatic arthritis, vitiligo, and alopecia areata. However, more robust studies are needed to assess long-term safety and establish treatment guidelines. JAK inhibitors are poised to become important additions to the therapeutic arsenal for a wide range of inflammatory skin conditions.

Table 1. First and second generation JAK inhibitors, their selectivity, and level of investigation in the treatment of dermatologic conditions. Adapted from Cinats, et al. ¹³ JAK inhibitors in which further investigation has been discontinued were excluded from this table.
Drug	Generation	Target	Status	Dermatologic Conditions
Ruxolitinib	1st	JAK1, JAK2	Phase II Phase III Phase II Phase III FDA-approved	Alopecia areata Vitiligo (topical) Psoriasis (topical) Graft-versus-host disease Atopic dermatitis (topical)
Tofacitinib	1st	JAK3, JAK1, JAK2 (with less selectivity)	Phase I Phase II Phase III Phase IV FDA-approved	Dermatomyositis Atopic dermatitis (topical) Psoriasis Alopecia areata Psoriatic arthritis
Baricitinib	1st	JAK1, JAK2	Phase II Phase II Phase III Phase III	Psoriasis Graft-versus-host disease Systemic lupus erythematosus Atopic dermatitis
Oclacitinib	1st	JAK1	FDA-approved	Canine allergic dermatitis
Upadacitinib	2nd	JAK1	Phase III FDA-approved	Atopic dermatitis Active psoriatic arthritis
Itacitinib	2nd	JAK1, JAK2	Phase II Phase II	Psoriasis Graft-versus-host disease
Filgotinib	2nd	JAK1	Phase II Phase II	Psoriatic arthritis Cutaneous lupus erythematosus
Abrocitinib	2nd	JAK1	Phase III	Atopic dermatitis
INCB54707	2nd	JAK1	Phase II	Hidradenitis suppurativa
Deucravacitinib	2nd	TYK2	Phase II Phase II Phase III	Systemic lupus erythematosus Psoriatic arthritis Psoriasis
Ritlecitinib	2nd	JAK3	Phase II Phase III	Vitiligo Alopecia areata
Brepocitinib	2nd	JAK1, TYK2	Phase II Phase II Phase II Phase II Phase II Phase II	Vitiligo Systemic lupus erythematosus Atopic dermatitis (topical) Alopecia areata Psoriatic arthritis Psoriasis
Gusacinitib	2nd	JAK1, JAK2, JAK3, TYK2, SYK	Phase IIb Phase IIb	Chronic hand eczema Atopic dermatitis
Delgocitinib	2nd	JAK1, JAK2, JAK3, TYK2	Phase IIb Phase IIb	Chronic hand eczema Atopic dermatitis
CTP-543	2nd	JAK1, JAK2	Phase III	Alopecia areata

Table 1. First and second generation JAK inhibitors, their selectivity, and level of investigation in the treatment of dermatologic conditions. Adapted from Cinats, et al. ¹³ JAK inhibitors in which further investigation has been discontinued were excluded from this table.

Drug

Generation

Target

Status

Dermatologic Conditions

Ruxolitinib

1st

JAK1, JAK2

Phase II
Phase III
Phase II
Phase III
FDA-approved

Alopecia areata
Vitiligo (topical)
Psoriasis (topical)
Graft-versus-host disease
Atopic dermatitis (topical)

Tofacitinib

1st

JAK3, JAK1, JAK2 (with less
selectivity)

Phase I
Phase II
Phase III
Phase IV
FDA-approved

Dermatomyositis
Atopic dermatitis (topical)
Psoriasis
Alopecia areata
Psoriatic arthritis

Baricitinib

1st

JAK1, JAK2

Phase II
Phase II
Phase III
Phase III

Psoriasis
Graft-versus-host disease
Systemic lupus erythematosus
Atopic dermatitis

Oclacitinib

1st

JAK1

FDA-approved

Canine allergic dermatitis

Upadacitinib

2nd

JAK1

Phase III
FDA-approved

Atopic dermatitis
Active psoriatic arthritis

Itacitinib

2nd

JAK1, JAK2

Phase II
Phase II

Psoriasis
Graft-versus-host disease

Filgotinib

2nd

JAK1

Phase II
Phase II

Psoriatic arthritis
Cutaneous lupus erythematosus

Abrocitinib

2nd

JAK1

Phase III

Atopic dermatitis

INCB54707

2nd

JAK1

Phase II

Hidradenitis suppurativa

Deucravacitinib

2nd

TYK2

Phase II Phase II Phase III

Systemic lupus erythematosus
Psoriatic arthritis
Psoriasis

Ritlecitinib

2nd

JAK3

Phase II
Phase III

Vitiligo
Alopecia areata

Brepocitinib

2nd

JAK1, TYK2

Phase II
Phase II
Phase II
Phase II
Phase II
Phase II

Vitiligo
Systemic lupus erythematosus
Atopic dermatitis (topical)
Alopecia areata
Psoriatic arthritis
Psoriasis

Gusacinitib

2nd

JAK1, JAK2, JAK3, TYK2, SYK

Phase IIb
Phase IIb

Chronic hand eczema
Atopic dermatitis

Delgocitinib

2nd

JAK1, JAK2, JAK3, TYK2

Phase IIb
Phase IIb

Chronic hand eczema
Atopic dermatitis

CTP-543

2nd

JAK1, JAK2

Phase III

Alopecia areata

Janus Kinase and Tyrosine Kinase Inhibitors in Dermatology

A Review of Their Utilization, Safety Profile and Future Applications

Conclusion

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Janus Kinase and Tyrosine Kinase Inhibitors in Dermatology

A Review of Their Utilization, Safety Profile and Future Applications

Conclusion

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