乌鸦传媒

BOSTON -- About half of patients with longstanding vitiligo obtained significant repigmentation that persisted for at least a year with the topical Janus kinase (JAK) inhibitor ruxolitinib (Opzelura), two randomized trials showed.

In one trial, 52.6% of patients randomized to ruxolitinib cream had at least 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) at 52 weeks. In the second trial, 48% of patients met F-VASI75 response criteria at 52 weeks. Patients in the trials who switched from placebo to ruxolitinib after 24 weeks also had substantial improvement at 52 weeks.

The most common treatment-related adverse events (TRAEs) with ruxolitinib were application-site acne and pruritus, reported David Rosmarin, MD, of Tufts Medical Center in Boston, during the American Academy of Dermatology (AAD) meeting here.

"Half of patients who applied ruxolitinib cream from day 1 achieved F-VASI75 and T-VASI50 [trunk] responses by week 52," said Rosmarin. "Efficacy at week 52 in crossover patients, after 28 weeks of ruxolitinib cream, was consistent with week-24 data in patients who applied ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, and no serious treatment-related adverse events were reported."

Also at AAD, preliminary data from a trial of oral JAK inhibitor ritlecitinib, presented by Yuji Yamaguchi, MD, PhD, of Pfizer, provided evidence that the drug halted progression of active vitiligo lesions and induced repigmentation in stable lesions, with consistent results for up to 48 weeks across the range of Fitzpatrick skin types.

Long-Term Ruxolitinib Outcomes

Rosmarin previously reported the primary outcome for the TRuE-V1 and TRuE-V2 trials, which showed that ruxolitinib 1.5% cream BID significantly increased the F-VASI75 response rate at 24 weeks versus vehicle. The updated report included ruxolitinib-treated patients who continued the JAK inhibitor to week 52, as well as placebo-treated patients who switched to ruxolitinib after completing the 24-week randomized trial.

The two trials included a combined total of 674 patients 12 years and older with nonsegmental vitiligo. They were randomized 2:1 to topical ruxolitinib or vehicle, and the primary outcomes were F-VASI75, F-VASI50, F-VASI90, T-VASI50, and a Vitiligo Noticeability Scale (VNS) rating of "a lot less noticeable" or "no longer noticeable."

In the TRuE-V1 trial, the F-VASI75 response rate with continuous ruxolitinib increased from 29.8% to 52.6% from week 24 to week 52. The rate in placebo patients increased from 7.4% at 24 weeks to 26.8% after 28 weeks of topical ruxolitinib. In TRuE-V2, the F-VASI75 response rates increased from 30.9% and 11.4% at 24 weeks with ruxolitinib and placebo, respectively, to 48.0% and 29.6% at 52 weeks.

The F-VASI90 response rate from week 24 to week 52 increased from 15.3% to 32.9% with continuous ruxolitinib and from 2.2% to 12.2% among patients who switched from placebo to ruxolitinib in TRuE-V1. Rates in TRuE-V2 increased from 16.3% to 27.7% with continuous ruxolitinib and from 1.3% to 16.0% with the placebo-switch group.

Three-fourths of patients on continuous ruxolitinib had F-VASI50 responses by week 52 in both trials, as did more than half of patients originally allocated to placebo and then switched to ruxolitinib. Half of patients in both trials met criteria for truncal (T-VASI50) response at week 52, as did 20-30% of patients switched from placebo to the JAK inhibitor. VNS response rates at 52 weeks were 39.9% and 32.8% with continuous ruxolitinib in TRuE-V1 and TRuE-V2, as compared with 15-20% of patients originally allocated to placebo.

Oral JAK Inhibitor

Ritlecitinib, an oral JAK3/TEC inhibitor, significantly improved F-VASI scores at 24 weeks in a randomized, placebo-controlled phase IIb trial involving patients with active nonsegmental vitiligo. A new analysis focused on the drug's efficacy in active versus stable lesions, as reported by Yamaguchi in a poster presentation at AAD.

The analysis included 364 patients randomized to placebo or one of five ritlecitinib dosing groups: 10 mg, 30 mg, 50 mg, and 50 mg with either 200 mg or 100 mg loading doses. The results showed that the 50-mg dose (with or without loading doses) and the 30-mg dose significantly reduced depigmentation versus placebo in active lesions (P=0.0096 to P=0.0090).

In stable lesions, statistically significant repigmentation occurred with all but the 10-mg dose of ritlecitinib, whereas placebo was associated with no change in lesion status (P=0.0016 to P=0.0090).

In a separate presentation, Yamaguchi reported an efficacy analysis for the different ritlecitinib doses by , including patients who completed a 24-week extension phase. The study accrued a total of 247 patients with Fitzpatrick skin type I-III and 117 patients with type IV-VI. Data for patients allocated to the 50-mg dosing schedules and to the lower doses were separately pooled.

At the end of the 24-week dose-ranging period, Fitzpatrick I-III patients treated with 50 mg of ritlecitinib had a 15.2% reduction in F-VASI versus placebo (P=0.0043), and patients treated with the lower doses had a 5.5% reduction (P=0.1991). Patients with Fitzpatrick IV-VI had 37.4% and 15.7% improvement with ritlecitinib versus placebo (P<0.0001, P<0.0401).

At a 24-week extension period, patients continuously treated with ritlecitinib had F-VASI improvement of 51-63% versus placebo for patients with Fitzpatrick I-III and differences of 51-68% for Fitzpatrick IV-VI.

"Continuous repigmentation without plateau of efficacy was observed at week 48 in Fitzpatrick skin types I-III and IV-VI," said Yamaguchi.