The Other JAK Inhibitors for Vitiligo

When the FDA approved Opzelura as a treatment for nonsegmental vitiligo in July, the agency heralded the whitish cream as the “first FDA-approved pharmacologic treatment to address regimentation in vitiligo patients.” Opzelura had been previously approved as treatment for atopic dermatitis.

Opzelura contains ruxolitinib, an inhibitor of Janus-activated kinases (JAKs) and, more specifically, the JAK1 and JAK2 (there is also JAK3 and tyrosine kinase 2 in the JAK family of enzymes). The Janus kinases are believed to play a key role in orchestrating the complicated signaling pathways for cytokines and growth factors.

Ruxolitinib may have some company. A number of other JAK inhibitors are under investigation as treatments for vitiligo, an autoimmune disordered characterized by whitish areas of skin that are the result of a loss of melanocytes. Melanocytes produce melanin, a dark skin pigment.

A review article published recently in Frontiers in Immunology about advances in vitiligo treatment listed five JAK inhibitors as candidates for vitiligo treatment. Even so, the FDA-approved label for Opzelura has a pointed reminder that the relationship between the JAKs and their inhibition and vitiligo isn’t entirely understood. The label says that the “relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.”

Here are six JAK inhibitors discussed in the Frontiers in Immunology review:

Tofacitinib is a JAK1 and JAK3 that is the active ingredient in Xeljanz. The review article says that five- to 10-milligram (mg) doses once or twice a day have shown some effectiveness as treatment for vitiligo. But review also mentions side effects from the oral version, including infections, cancer and cytopenia, and it suggests that a topical version may therefore be preferred. The review discusses positive results from a small (11 patients) trial of a tofacitinib cream.

Baricitinib is a JAK1 and JAK2 inhibitor that is the active ingredient in Olumiant. The review article says that there has been a case report of repigmentation in vitiligo in patients taking four-mg doses of baricitinib as a treatment for rheumatoid arthritis. According to the review, there is a phase 2 trial underway evaluating baricitinib in combination with phototherapy as a treatment for vitiligo.

Ifidancitinib, also known provisionally as ATI-50002, is a JAK1 and JAK3 inhibitor. It is also under investigation as a treatment for alopecia areata,

Ritlecitinib, also known provisionally as PF-06651600, is a JAK3 and tyrosine kinase inhibitor. It is being evaluated in a clinical trial as a treatment for vitiligo along with another experimental agent, brepocitinib, a JAK1 and tyrosine kinase inhibitor that has the provisional code name of PF-0670084.

Pfizer put out a press release earlier this month to announce that the FDA had accepted its application for ritlecitinib as a treatment for alopecia areata and that the FDA is expected to make an approval decision during the second quarter of next year.

In June, Pfizer issued a press release trumpeting the phase 2 trial results for oral brepocitinib as a treatment for psoriatic arthritis, plaque psoriasis, ulcerative colitis, alopecia areata and hidradenitis suppurativa.

Cerdulatinib is a spleen tyrosine kinase inhibitor as a well as a JAK inhibitor. According to the federal government’s clinical trial database, clinicaltrials.gov, a small trial of a cerdulatinib gel as a vitiligo treatment was completed in 2020 but no results are posted on the clinicaltrials.gov. Researchers are also evaluating cerdulatinib as a cancer drug and, more specifically, as an agent might be used to treat patients with non-Hodgkin lymphoma and peripheral T-cell lymphoma.