Biologics and Beyond

The dermatology treatment landscape continues to expand, as does the range of uses for existing and emerging treatments. Whereas TNF-alpha inhibitors are approved for dermatologic indications of psoriasis, psoriatic arthritis, and hidradenitis suppurativa, JAK inhibitors are not yet approved for any dermatology indications. However, new approvals may be forthcoming.

Adriane A. Levin, MD, Director of the Atopic Dermatitis Program at Brigham and Women’s Hospital in Boston, discussed the off-label use of TNF-alpha inhibitors and JAK inhibitors in dermatology at the AAD Virtual Meeting Experience 2021 (VMX 2021) this spring. Ahead is a review of promising off-label uses.

TNF-alpha Inhibitors

Granuloma annulare. Commonly used medications for granuloma annulare (GA) include steroids—topically, intralesionally, and systemically, phototherapy, antimalarials, and immunosuppressive medications among others, Dr. Levin says. “We don’t know the exact pathophysiology of granuloma annulare. It does appear to be a TH1 mediated disease, and it seems to be a hypersensitivity reaction,” she observes. Although GA is generally idiopathic, it has been reported in conjunction with conditions such as diabetes and paraneoplastic processes or in association with certain drugs. TNF-alpha inhibitors have shown benefit in GA with one review finding that close to 80 percent of patients being treated with a TNF inhibitor for GA showed a response, Dr. Levin points out. She says adalimumab is the best represented TNF inhibitor in the literature for GA.

Of note, there are reports of TNF alpha-inhibitor-induced GA. “This derives predominantly from the rheumatology literature in which TNF inhibitors are used to treat unrelated rheumatologic disorders, such as rheumatoid arthritis. These patients for the most part developed generalized forms of GA and did not have any of the typically associated conditions that you might consider in GA,” Dr. Levin says.

Cutaneous sarcoidosis. Steroids, phototherapy, antimalarials, and immunosuppressive medications have been used for cutaneous sarcoidosis, but in a randomized double-blind study of 10 patients on adalimumab and six patients on placebo, adalimumab was associated with significant improvement at 12 weeks. Infliximab has also shown benefit in this disease.

Neutrophilic disease. Because TNF is essential in the activation and recruitment of neutrophils, anti-TNF therapies can be helpful for treatment, Dr. Levin says. “Dissecting scalp cellulitis can be a very difficult-to-treat and frustrating condition.” In one study of men with dissecting cellulitis, adalimumab provided dramatic improvement and resolution of symptoms within eight weeks.

Behcet’s disease. Several studies demonstrate efficacy of TNF inhibitors, Dr. Levin says, noting that one review found a clinical response rate in 90 percent of patients on TNF inhibitors and improvement in uveitis.

Vitiligo. The pathogenesis of vitiligo involves interferon gamma, JAK1 and 2, and CXCL10, Dr. Levin notes. Both oral tofacitinib and oral ruxolitinib have shown benefit. In one patient with alopecia and vitiligo, ruxolitinib provided improvement in both conditions. Twelve weeks after treatment discontinuation hair regrowth remained but some re-pigmentation was lost.

Multiple concentrations of topical ruxolitinib cream have been studied for vitiligo, each providing markedly significant improvement compared to vehicle, that persisted or improved to week 52, Dr. Levin says.

Alopecia areata. The evidence for oral JAK inhibitors in alopecia areata is less robust. In a trial of 90 patients treated with tofacitinib for alopecia areata, 77 percent of patients were found to have some clinical response, with 58 percent of them having greater than a 50 percent change in their SALT score over a four- to 18-month treatment, Dr. Levin notes.

Baricitinib is the first JAK inhibitor to demonstrate hair regrowth in a Phase 3 alopecia areata trial. At week 36, 52 percent of those in the baricitinib 4mg group and 33 percent in the 2mg group achieved a SALT score of less than 20.

Head-to-head trials of oral tofacitinib compared to oral ruxolitinib found no significant differences in efficacy or safety in patients with alopecia areata.