New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase–signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many ...different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.
Background Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA. Objective We sought to evaluate the safety and efficacy of the Janus kinase 1/3 ...inhibitor, tofacitinib, in a series of patients over an extended period of time. Methods This is a retrospective study of patients age 18 years or older with AA with at least 40% scalp hair loss treated with tofacitinib. The primary end point was the percent change in Severity of Alopecia Tool (SALT) score during treatment. Results Ninety patients met inclusion criteria. Of 65 potential responders to therapy, defined as those with alopecia totalis or alopecia universalis with duration of current episode of disease of 10 years or less or alopecia areata, 77% achieved a clinical response, with 58% of patients achieving greater than 50% change in SALT score over 4 to 18 months of treatment. Patients with AA experienced a higher percent change in SALT score than did patients with alopecia totalis or alopecia universalis (81.9% vs 59.0%). Tofacitinib was well tolerated, and there were no serious adverse events. Limitations The retrospective nature of the data, the relatively small number of patients, and lack of a control group are limitations. Conclusion Tofacitinib should be considered for the treatment of severe AA, alopecia totalis, and alopecia universalis; tofacitinib dose response will be better defined by randomized controlled trials.
IMPORTANCE: Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available. OBSERVATIONS: Recent advances in the ...understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation. CONCLUSIONS AND RELEVANCE: The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.
Background Treatment of moderate to severe atopic dermatitis (AD) is often inadequate. Objective We sought to evaluate the efficacy of the oral Janus kinase inhibitor tofacitinib citrate in the ...treatment of moderate to severe AD. Methods Six consecutive patients with moderate to severe AD who had failed standard treatment were treated with tofacitinib citrate. Response to treatment was assessed using the Scoring of AD index. Results Decreased body surface area involvement of dermatitis and decreased erythema, edema/papulation, lichenification, and excoriation were observed in all patients. The Scoring of AD index decreased by 66.6% from 36.5 to 12.2 ( P < .05) during 8 to 29 weeks of treatment. There were no adverse events. Limitations Small sample size, lack of placebo control group, and the possibility of bias are limitations. Conclusion The oral Janus kinase inhibitor tofacitinib citrate may be beneficial in the treatment of moderate to severe AD.
Background There are no reliably effective therapies for alopecia areata (AA). Objective We sought to evaluate the benefit and adverse effects of the Janus kinase 1/3 inhibitor, tofacitinib, in a ...series of adolescent patients with AA. Methods We reviewed the records of 13 adolescent patients with AA treated with tofacitinib. Severity of disease was assessed using the Severity of Alopecia Tool (SALT). Adverse events were evaluated by laboratory monitoring, physical examinations, and review of systems. Results Thirteen patients, aged 12 to 17 years, with AA were treated with tofacitinib. Nine patients experienced clinically significant hair regrowth. Median percent change in SALT score was 93% (mean 61%; 1%-100%) at an average of 6.5 months of treatment. Adverse events were mild. Limitations Limitations include the retrospective nature of the data, small sample size, and lack of a control group. Conclusion Tofacitinib is a promising therapy for AA in adolescents. The use of tofacitinib and other Janus kinase inhibitors for the treatment of AA in this age group should be further evaluated in prospective clinical trials.
Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors.
To evaluate ...the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo.
This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation.
Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration.
Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group.
Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.
Alopecia areata (AA) is a common skin disease that is frequently emotionally devastating. Several studies have examined the effect of AA on health-related quality of life (HRQoL). We performed a ...systematic review of all published studies of HRQoL in patients with AA. Eleven studies met inclusion criteria, incorporating data from 1986 patients. Patients with AA consistently demonstrate poor HRQoL scores, with greater extent of scalp involvement associated with lower HRQoL. HRQoL experienced by patients with AA is similar to that seen in patients with other chronic skin diseases including atopic dermatitis and psoriasis.
Janus kinase inhibitors for alopecia areata King, Brett A.; Craiglow, Brittany G.
Journal of the American Academy of Dermatology,
08/2023, Letnik:
89, Številka:
2
Journal Article
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