significantly reduced Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores after 3 months (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P=0.0005).6 Recalcitrant juvenile and adult DM treated with ruxolitinib 10 to 15 mg twice daily for 6 to 12 months was successful in multiple case reports and series.7-9
Graft-Versus-Host Disease
Graft-versus host disease (GVHD) frequently results in cutaneous involvement and in treatment-resistant patients, oral ruxolitinib 10 mg twice daily has been reported to improve symptoms within 1 to 2 weeks.10 Studies in mouse models of GVHD show that tofacitinib similarly treats GVHD and actually prevents GVHD by modulating the CD8 T-cell response following bone marrow transplants.11
Granuloma Annulare
Granuloma annulare (GA) is another cutaneous disease for which little progress has been witnessed in treatment options, though JAK inhibitors may change this soon. Multiple cases and studies with tofacitinib for GA indicate promising results.12 Tofacitinib 5 mg twice daily led to a significant improvement in GA after 6 months, such that 3 of 5 patients treated experienced complete GA resolution, and the remaining 2 patients experienced 61%-70% reduction in body surface area involvement.13
Hidradenitis Suppurativa
In a case series of 2 patients with treatment-resistant hidradenitis suppurativa (HS), tofacitinib 5 mg twice daily reduced ulceration, drainage, and pain after 3 to 4 months and allowed other therapies, like cyclosporine, to be discontinued.14 One study found significant benefit in patients with HS who were treated with upadacitinib 15 mg daily after several months, and therefore upadacitinib is currently in phase II trials for HS.15,16
Lichen Planus
JAK inhibitors also show promise in treating lichen planus (LP), particularly erosive lichen planus (ELP) and lichen planopilaris (LPP). One case series of 3 patients with LP and ELP treated with tofacitinib 5 mg twice daily noted significant improvement of symptoms within 1 to 3 months.17 Similarly, another case series of LPP patients treated with tofacitinib 5 mg twice to three times daily showed success in 80% of patients after 6 to 12 months, and noted that some patients who did not respond to 5 mg twice daily did respond to 5 mg 3 times daily.18
Necrobiosis Lipoidica
Success in treating necrobiosis lipoidica (NL) with JAK inhibitors has been reported in a few cases. One patient with polycythemia vera (PV) and NL treated with ruxolitinib 10 mg twice daily experienced almost complete resolution of active NL after 3 months.19 Additionally, another patient treated with tofacitinib 5 mg twice daily and intralesional corticosteroids had complete re-epitheliazation of prior ulcerations after 6 weeks.20
Psoriasis
Tofacitinib is approved for PsA and reports indicate that successful treatment of PsA also improves comorbid plaque psoriasis.21 After 16 weeks, 40% of patients taking tofacitinib 5 mg twice daily achieved a psoriasis area and severity index (PASI) score of 75, and 59% of those at the 10-mg twice daily dosing achieved a PASI75.22 A meta-analysis of 3743 psoriasis patients treated with tofacitinib 5 to 10 mg twice daily concluded that tofacitinib was safe and effective at treating plaque psoriasis.23 Comparably, after 12 weeks, 43% of patients treated with baricitinib 8 mg daily achieved a PASI75, as did 54% of the patients in the 10 mg daily group. Topical ruxolitinib 0.5%-1.5% has also been studied in psoriasis, and while efficacy of the lower dose was similar to vehicle, the 1.0% and 1.5% dosages resulted in 53% and 54% reduced lesion scores compared to 32% for the vehicle.24
Pyoderma Gangrenosum
In a case series of 2 patients with treatment resistant pyoderma gangrenosum (PG), baricitinib 4 mg lead to resolution and re-epithelization of a scalp PG in 5 weeks and lower leg PG in 3 months.25 Similarly, 3 patients with Crohn’s disease and treatment-resistant PGs were started on tofacitinib 5 mg twice daily and all 3 patients experienced resolution within 1 to 3 months on therapy.26
Sarcoidosis
Sarcoidosis is another T-cell mediated dermatosis that is responsive to inhibition of the JAK pathway. Specifically tofacitinib 5 mg twice daily for 3 months lead to resolution of cutaneous lesions in 3 to 10 months.12,27,28 In another case report, ruxolitinib 10 mg twice daily for PV resulted in resolution of the patients cutaneous sarcoidosis after 5 months.29
Systemic and Cutaneous Lupus
An altered JAK/STAT pathway has been implicated in the pathophysiology of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).30 One clinical trial with baricitnib found that a 2-mg daily dose did not improve symptoms of SLE, whereas a 4-mg daily dose resolved symptoms of arthritis and skin rashes.31 In a case series of 3 patients with CLE, tofacitinib 5 mg twice daily resulted in resolution of skin lesions within 4 to 7 months.32
Morphea/Systemic Sclerosis
Morphea and systemic sclerosis was found to respond well to JAK inhibition; specifically tofacitinib 5 to 10 mg twice daily, baricitnib 2 to 4 mg daily, and ruxolitinib 10 mg twice daily have been reported as successful therapies for morphea and
Graft-Versus-Host Disease
Graft-versus host disease (GVHD) frequently results in cutaneous involvement and in treatment-resistant patients, oral ruxolitinib 10 mg twice daily has been reported to improve symptoms within 1 to 2 weeks.10 Studies in mouse models of GVHD show that tofacitinib similarly treats GVHD and actually prevents GVHD by modulating the CD8 T-cell response following bone marrow transplants.11
Granuloma Annulare
Granuloma annulare (GA) is another cutaneous disease for which little progress has been witnessed in treatment options, though JAK inhibitors may change this soon. Multiple cases and studies with tofacitinib for GA indicate promising results.12 Tofacitinib 5 mg twice daily led to a significant improvement in GA after 6 months, such that 3 of 5 patients treated experienced complete GA resolution, and the remaining 2 patients experienced 61%-70% reduction in body surface area involvement.13
Hidradenitis Suppurativa
In a case series of 2 patients with treatment-resistant hidradenitis suppurativa (HS), tofacitinib 5 mg twice daily reduced ulceration, drainage, and pain after 3 to 4 months and allowed other therapies, like cyclosporine, to be discontinued.14 One study found significant benefit in patients with HS who were treated with upadacitinib 15 mg daily after several months, and therefore upadacitinib is currently in phase II trials for HS.15,16
Lichen Planus
JAK inhibitors also show promise in treating lichen planus (LP), particularly erosive lichen planus (ELP) and lichen planopilaris (LPP). One case series of 3 patients with LP and ELP treated with tofacitinib 5 mg twice daily noted significant improvement of symptoms within 1 to 3 months.17 Similarly, another case series of LPP patients treated with tofacitinib 5 mg twice to three times daily showed success in 80% of patients after 6 to 12 months, and noted that some patients who did not respond to 5 mg twice daily did respond to 5 mg 3 times daily.18
Necrobiosis Lipoidica
Success in treating necrobiosis lipoidica (NL) with JAK inhibitors has been reported in a few cases. One patient with polycythemia vera (PV) and NL treated with ruxolitinib 10 mg twice daily experienced almost complete resolution of active NL after 3 months.19 Additionally, another patient treated with tofacitinib 5 mg twice daily and intralesional corticosteroids had complete re-epitheliazation of prior ulcerations after 6 weeks.20
Psoriasis
Tofacitinib is approved for PsA and reports indicate that successful treatment of PsA also improves comorbid plaque psoriasis.21 After 16 weeks, 40% of patients taking tofacitinib 5 mg twice daily achieved a psoriasis area and severity index (PASI) score of 75, and 59% of those at the 10-mg twice daily dosing achieved a PASI75.22 A meta-analysis of 3743 psoriasis patients treated with tofacitinib 5 to 10 mg twice daily concluded that tofacitinib was safe and effective at treating plaque psoriasis.23 Comparably, after 12 weeks, 43% of patients treated with baricitinib 8 mg daily achieved a PASI75, as did 54% of the patients in the 10 mg daily group. Topical ruxolitinib 0.5%-1.5% has also been studied in psoriasis, and while efficacy of the lower dose was similar to vehicle, the 1.0% and 1.5% dosages resulted in 53% and 54% reduced lesion scores compared to 32% for the vehicle.24
Pyoderma Gangrenosum
In a case series of 2 patients with treatment resistant pyoderma gangrenosum (PG), baricitinib 4 mg lead to resolution and re-epithelization of a scalp PG in 5 weeks and lower leg PG in 3 months.25 Similarly, 3 patients with Crohn’s disease and treatment-resistant PGs were started on tofacitinib 5 mg twice daily and all 3 patients experienced resolution within 1 to 3 months on therapy.26
Sarcoidosis
Sarcoidosis is another T-cell mediated dermatosis that is responsive to inhibition of the JAK pathway. Specifically tofacitinib 5 mg twice daily for 3 months lead to resolution of cutaneous lesions in 3 to 10 months.12,27,28 In another case report, ruxolitinib 10 mg twice daily for PV resulted in resolution of the patients cutaneous sarcoidosis after 5 months.29
Systemic and Cutaneous Lupus
An altered JAK/STAT pathway has been implicated in the pathophysiology of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).30 One clinical trial with baricitnib found that a 2-mg daily dose did not improve symptoms of SLE, whereas a 4-mg daily dose resolved symptoms of arthritis and skin rashes.31 In a case series of 3 patients with CLE, tofacitinib 5 mg twice daily resulted in resolution of skin lesions within 4 to 7 months.32
Morphea/Systemic Sclerosis
Morphea and systemic sclerosis was found to respond well to JAK inhibition; specifically tofacitinib 5 to 10 mg twice daily, baricitnib 2 to 4 mg daily, and ruxolitinib 10 mg twice daily have been reported as successful therapies for morphea and
