麻豆传媒

NEW ORLEANS -- Patients who discontinued topical ruxolitinib (Opzelura) for vitiligo retained new pigmentation for as long as a year, according to a study of planned withdrawal.

Almost 40% of patients maintained their response for a year. An additional 28.6% of patients in the withdrawal arm had vitiligo relapse, but most regained response when they restarted the topical therapy. Among a small number of patients who relapsed during treatment, three-fourths regained response when they continued ruxolitinib.

No serious treatment-emergent adverse events (TEAEs) occurred during 104 weeks of follow-up, reported John E. Harris, MD, PhD, of the University of Massachusetts Chan Medical School in Worcester, during the American Academy of Dermatology annual meeting.

"If you stopped the drug, just like everything else, the vitiligo tends to come back," said Harris. "Not in everyone, as there is a population who will maintain their repigmentation even off the drug. If you restart the drug, you can regain the response."

A separate analysis showed that response rates continued to increase among patients who remained on topical ruxolitinib during a maintenance phase out to 104 weeks.

The findings came from a randomized withdrawal arm of the phase III TRuE-V trials evaluating 1.5% ruxolitinib cream in adolescent and adult patients with nonsegmental vitiligo. The results showed that about 30% of patients achieved the primary endpoint of at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) at 1 year.

Harris reported results in patients who met the more stringent response criteria of F-VASI90 and then were randomized to continue ruxolitinib or to receive vehicle for an additional year. The objectives were to evaluate the time to relapse (defined as <F-VASI75) and the duration of F-VASI90 response during the randomized withdrawal period.

The randomized withdrawal study included 116 patients who had ≥F-VASI90 response at 52 weeks. During an additional 52 weeks of follow-up, 39% of patients randomized to withdrawal maintained ≥F-VASI75 response to 104 weeks. Harris said 28.6% of patients in the withdrawal arm relapsed and that about half of the relapses occurred within 4 months after the switch to vehicle. An additional 23.2% of patients in the withdrawal arm discontinued treatment prior to 1 year.

The results also showed that 21.4% of patients in the withdrawal arm maintained ≥F-VASI90 response for a year, as did 61.8% of patients randomized to continue topical ruxolitinib. The median duration of ≥F-VASI90 response in the withdrawal arm was 195 days versus not estimable for patients who continued topical ruxolitinib.

Among patients with relapse after withdrawal of ruxolitinib, 12 of 16 regained ≥F-VASI75 response after a median follow-up of 12 weeks after restating active therapy. Harris said 11 of 16 patients regained ≥F-VASI90 response a median of 15 weeks after restarting ruxolitinib.

Mild or moderate TEAEs associated with ruxolitinib applications consisted of one case each of application-site dermatitis, application-site rash, and hyperlipidemia.

"If your patients lose pigment after withdrawing ruxolitinib, they can put it back on and regain it," said Harris. "Interestingly, some patients who continued ruxolitinib relapsed but continued to use the drug and were able to regain the lost pigment. That's evidence that there is some waxing and waning of this disease, even during ongoing treatment."

TRuE investigators also examined outcomes in patients who did not attain a ≥F-VASI90 response after 52 weeks but remained on ruxolitinib during a 52-week maintenance phase. The proportion of patients who met the primary endpoint (≥F-VASI75) increased from 31% at 52 weeks to 66% at 104 weeks, reported David Rosmarin, MD, of Indiana University School of Medicine in Indianapolis. The percentage of ≥F-VASI90 responders increased from 2.3% at week 52 to 33.8% at week 104.

Similarly, the percentage of patients who achieved a total (T)-VASI score ≥T-VASI50 increased from 42.5% to 63.8%

Among patients who switched from vehicle to ruxolitinib at 52 weeks, the F-VASI75 response rate increased from 16% to 47% and F-VASI90 response rate from 0% to 28%. The T-VASI50 response rate increased from 16.9% at 52 weeks to 54.8% at 104 weeks.

During a discussion that followed the presentations, Harris said investigators did not have an opportunity to identify potential biomarkers for patients who achieved exceptional response or, conversely, who did not respond to the treatment.