M. Zallmann1, A.H. Chong1,2
Tofacitinib is a first-generation inhibitor of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, a novel target for immune-mediated and inflammatory diseases (IMIDs). A preferential inhibitor of JAK1/3 over JAK2, tofacitinib is currently the most studied JAK-inhibitor for cutaneous-disease.
We present the findings of a literature review on the efficacy, safety and monitoring requirements of tofacitinib in dermatological IMIDs. Through analysis of tofacitinib, we introduce the key clinical considerations for JAK-inhibitor use in dermatology.
The highest level of evidence for tofacitinib efficacy exists for chronic plaque psoriasis (CPP) and atopic dermatitis (AD) in phase III and IIa studies respectively. Tofacitinib demonstrated statistically significant superiority over placebo in phase III RCTs for moderate-severe CPP (39.9%– 55.6% and 59.2%–68.8% achieved PASI75 with 5 and 10 mg PO BD respectively).
In mild-moderate AD, EASI90 was achieved with topical 2% tofacitinib ointment after 2 and 4 weeks.
Promising efficacy in alopecia areata (AA) with oral tofacitinib was reported in retrospective reviews (SALT50 in 58%) and case series. Treatment efficacy in alopecia universalis (AU) associated nail dystrophy, nail psoriasis and vitiligo has been suggested in case reports and case series.
The commonest adverse events with tofacitinib were nasopharyngitis/URTI, headache and asymptomatic creatinine phosphokinase (CK) elevations. A characteristic safety-profile has emerged for tofacitinib and other JAKinhibitors, however, nuances occur as a result of their relative potency/selectivity against JAK1-3 and Tyk2. Emerging literature indicates promising efficacy and safety for tofacitinib and points-to exciting potential of JAK-inhibitors as novel-therapeutics in dermatology.