Janus Kinase (JAK) inhibitors are arguably the hottest topic in dermatology (if not all of medicine). The pipeline is almost bursting, and enthusiasm for these agents is palpable as data mounts. Brett King, MD, PhD, a Yale Medicine dermatologist and associate professor of dermatology at Yale School of Medicine in New Haven, CT, pioneered the use of JAK inhibitors in dermatology. He spoke to Practical Dermatology® magazine about the major role that JAK inhibitors may have in treating skin diseases in the future.
What are some of the dermatologic skin diseases that may benefit from JAK inhibitors?
Brett King, MD, PhD: The reason JAK inhibitors are going to revolutionize dermatology is the broad spectrum of diseases for which they are demonstrating efficacy. There is published data to support the use of JAK inhibitors for alopecia areata (AA), atopic dermatitis, chronic actinic dermatitis (AD), cutaneous Graft-versus-host disease (GVHD), dermatomyositis, erythema multiforme, granuloma annulare and sarcoidosis, hypereosinophilic syndrome with cutaneous involvement, lichen planus, morphea and eosinophilic fasciitis, pruritus, psoriasis, and vitiligo. Truly, JAK inhibitors stand alone as the single class of medication with such reach within dermatology. Furthermore, there will be both oral and topical JAK inhibitors. Because JAK inhibitors will have such broad reach across dermatology, they will not only be impossible to ignore but there will be (at least) a hundred reasons (i.e. patients) for every dermatologist to want to become comfortable with their use. We became physicians to improve life for others, and JAK inhibitors are going to permit treatment of several previously refractory diseases, facilitating what we are trying to achieve like no other class of medicine ever before.
The JAK pipeline is robust. Which agents seem most promising?
Dr. King: Indeed, there are several JAK inhibitors in clinical trials in dermatology, but there is not yet a lot of published Phase 3 clinical trial data. The recent data for abrocitinib (Pfizer) in moderate to severe AD are really promising; the data for baricitinib (Olumiant, Eli Lilly) in AD are good, too. Published Phase 2 results of ruxolitinib 1.5% cream (Incyte) in mild to moderate AD and of the TYK2 inhibitor BMS-986165 (Bristol-Myers Squibb Company) in psoriasis are provocative. Meanwhile, there have been oral presentations regarding trials of JAK inhibitors for AA, i.e. ritlecitinib (Pfizer) and CTP-543 (Concert), and vitiligo i.e., ruxolitinib 1.5% cream, the results of which look promising but are yet unpublished.
Any safety signals?
Dr. King: We don’t know yet because we don’t yet have large data sets from dermatology clinical trials. The JAK inhibitors tofacitinib, baricitinib, and upadacitinib have a black box warning for cancer, infection, and venous thromboembolism. It is important to consider, though, that this warning emerged from trials in rheumatoid arthritis, and in these trials the vast majority of patients were taking concomitant methotrexate and sometimes prednisone or NSAIDs, as well. It is noteworthy that in clinical trials of tofacitinib in ulcerative colitis, there were no cases of malignancy. We, as dermatologists, want to be informed by the safety data from dermatology clinical trials, which may not resemble that in rheumatology.
What will the next year bring in terms of JAK inhibitors in dermatology?
Dr. King: JAK inhibitor clinical trials in AD are the farthest along, and we’ve recently seen published Phase 3 results of abrocitinib and baricitinib. Hopefully, the next year will see FDA approval of a JAK inhibitor for AD. JAK inhibitors for AA, vitiligo, and other diseases are behind AD but should be coming in the next two to three years.
Any update on topical JAK inhibitors?
Dr. King: Yes, and it’s exciting. Recently we’ve seen published Phase 2 clinical trial data for ruxolitinib 1.5% cream in AD. Not only does it appear to have great efficacy but ruxolitinib 1.5% cream seems be more efficacious than triamcinolone 0.1% cream. It seems that we may, at last, have a non-steroidal topical for AD that has potency rivaling a topical steroid! Meanwhile, ruxolitinib 1.5% cream failed to reverse alopecia areata, but data presented at recent meetings suggests that it may have some efficacy for the treatment of facial vitiligo.