JAK inhibitors in vitiligo

A mouse-model study suggests that the IFNγ/CXCL10 axis plays a role in the pathogenesis of vitiligo. Moreover, a recently published proof-of-concept study showed that a cream containing the Janus kinase (JAK) inhibitor ruxolitinib is indeed effective in vitiligo [1,2].

Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8⁺ T cells in their skin and blood, which are directly responsible for melanocyte destruction. In addition, gene expression in lesional skin from vitiligo patients revealed an IFNγ-specific signature, including the chemokine CXCL10. Experimental data in a mouse model identified a critical role for CXCL10 in both the progression and maintenance of vitiligo, thereby supporting inhibition of CXCL10 as a targeted treatment strategy for vitiligo patients [3]. Since IFNγ signal transduction occurs through JAK1 and 2, JAK inhibitors could lead to blockade of IFNγ signalling and downstream CXCL10 expression. Indeed, a case report published in 2015 showed a treatment success with tofacitinib in a patient with vitiligo [4]. Another case report showed rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata [5]. “In this case report, skin repigmentation went hand in hand with a significant reduction of CXCL10,” explained Dr Mehdi Rashighi (Massachusetts Medical School, USA) during his presentation [1].

The latest proof-of-concept study for JAK inhibition in vitiligo was published recently [2]. In this randomised, double-blind, phase 2 study, adult patients with vitiligo were treated with ruxolitinib cream in different doses (0.15% up to 1.5% twice daily). The primary endpoint was the proportion of patients achieving a 50% or higher improvement from baseline in the facial Vitiligo Area Severity Index (F-VASI) at week 24. In the highest dose group, 30.3% of patients achieved this endpoint, a percentage that increased to 51.5% after 52 weeks. At this time, a third of the patients even gained an F-VASI-90 response. “Clearly, the best response was seen with the 1.5% ruxolitinib cream applied twice daily,” Dr Rashighi stated. The tolerability of the cream was good; only acne was seen more frequently than in the vehicle group. Enrolment for a phase 3 trial with this cream is already completed.

“Hopefully, within the next 5-8 years, we will have more therapeutic options in vitiligo,” concluded Dr Rashighi.

1. 
   
   1. Rashighi M. JAK family inhibitors – In vitiligo. D1T06.3A, EADV 2020 Virtual Congress, 29-31 Oct.
   2. Rosmarin D, et al. Lancet 2020;396:110-20.
   3. Rashighi M, et al. Sci Transl Med 2014;6:223ra23.
   4. Craiglow BG, King BA. JAMA Dermatol 2015;151:1110-2.
   5. Harris JE, et al. J Am Acad Dermatol 2016;74:370-1.

Posted on 17 December, 202018 December, 2020