Targeted Oral Drug Plus UV Therapy May Help in Extensive Vitiligo

Combining ultraviolet (UV) phototherapy with the Janus kinase (JAK) inhibitor baricitinib (Olumiant) helped patients with extensive vitiligo see significantly more repigmentation compared with a placebo group in a “proof-of-concept” trial, researchers said.

Patients assigned to the drug saw a mean decrease in Vitiligo Area Scoring Index (VASI) values of 44.8% (95% CI 31.3-58.4) after 36 weeks, compared with 9.2% (95% CI -24.7 to 27.7) among patients receiving placebo plus phototherapy, according to Julien Seneschal, MD, PhD, of University Bordeaux in France, and colleagues in JAMA Dermatology.

This outcome was actually somewhat disappointing, as the degree of repigmentation differed little from that seen with ultraviolet light therapy alone in a study conducted more than 20 years ago. In that study, phototherapy led to a mean VASI reduction of 42.9% after 6 months.

As well, the current trial introduced phototherapy when patients had been taking baricitinib or placebo for 12 weeks. At that point, not much repigmentation had occurred in either group, suggesting that baricitinib may not do much good by itself.

But Seneschal and colleagues were not discouraged overall. The trial “highlighted the efficacy of combining the JAK1/JAK2 inhibitor baricitinib with narrowband UV-B in the treatment of adults with active vitiligo,” they wrote. “It is a valuable contribution to the growing interest in the use of JAK inhibitors to treat autoimmune conditions and justifies the completion of a larger confirmatory phase III trial in the future.”

The general idea, the group explained, is that JAK inhibition serves to arrest the autoimmune process in vitiligo, while the phototherapy is what actively promotes repigmentation by stimulating melanocyte differentiation and proliferation.

Another JAK inhibitor — ruxolitinib — is already approved as a topical formulation (Opzelura) to treat vitiligo. But the indication is only for vitiligo affecting the face and no more than 10% of the total skin surface. An oral systemic therapy would likely be more suitable for patients with extensive vitiligo. Indeed, several reports have indicated that other JAK inhibitors such as tofacitinib (Xeljanz) have been helpful in a few individual cases. But the current study, called BARVIT and sponsored by baricitinib’s manufacturer, Eli Lilly, appears to be the first to test an oral JAK inhibitor in a systematic, controlled trial.

Seneschal and colleagues randomized a total of 49 patients in a 3:1 ratio to 4 mg/day baricitinib or placebo. VASI score was the primary outcome measure. Patients were required to have nonsegmental vitiligo covering at least 5% of their bodies, excluding hands and feet. As described above, the oral treatments were given for 12 weeks, then narrowband UV-B phototherapy was added for another 24 weeks. Median patient age was approximately 50 and some 70% were women. At baseline, the median VASI score was 16.

Responder analyses clearly favored the baricitinib group. Some 53% of those patients achieved VASI reductions of 50%, and 27% had reductions of 75% by week 36; in the placebo group, just one patient had a 50% decrease and none saw a reduction of 75%. The same pattern was seen for improvement of facial vitiligo.

Secondary outcomes including the Vitiligo Extent Score and Vitiligo European Task Force assessment-extent at week 36 were also better with baricitinib, but some others, such as the Vitiligo Signs of Activity Score, didn’t differ between groups.

Encouragingly, improvement continued right up to the final assessment at week 36. “[I]t could be assumed that continuing this strategy for a longer period of time may result in further increase in repigmentation,” the researchers offered.

Like other JAK inhibitors, baricitinib comes with an array of boxed warnings about increased risk for infections, cardiovascular events, and malignancies. But in this small, relatively short trial, no major differences in adverse event rates were seen between the baricitinib and placebo groups, and none were out of the ordinary for a JAK inhibitor.

The small sample size was the study’s main limitation; also, the researchers noted, “the impact of JAK inhibitors alone on repigmentation was not well characterized.”