BOSTON — About half of patients with long-standing vitiligo achieved significant repigmentation that persisted for at least a year with the topical Janus kinase (JAK) inhibitor ruxolitinib (Opzelura), two randomized trials have shown.
In one trial, 52.6% of patients randomized to ruxolitinib cream had at least a 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75) at 52 weeks. In the second trial, 48% of patients met the F-VASI75 response criteria at 52 weeks. Patients in the trials who switched from placebo to ruxolitinib after 24 weeks also showed substantial improvement at 52 weeks.
The most common treatment-related adverse events with ruxolitinib were application site acne and pruritus, reported David Rosmarin, MD, of Tufts Medical Center in Boston, at the American Academy of Dermatology meeting. (ADA) here.
“Half of the patients who applied ruxolitinib cream on day one achieved F-VASI75 and T-VASI50 [trunk] responses at week 52,” Rosmarin said. “Efficacy at week 52 in crossover patients, after 28 weeks of ruxolitinib cream, was consistent with data at week 24 in patients who applied ruxolitinib from day 1. Ruxolitinib cream was well tolerated and no serious treatment-related adverse events were reported. »
Also at the AAD, preliminary data from a trial of ritlecitinib, an oral JAK inhibitor, presented by Yuji Yamaguchi, MD, PhD, of Pfizer, provided evidence that the drug halted the progression of vitiligo lesions. active and induces repigmentation in stable lesions, with consistent results for up to 48 weeks for all Fitzpatrick skin types.
Long-term results of ruxolitinib
Rosmarin previously reported the primary outcome of the TRuE-V1 and TRuE-V2 trials, which showed that ruxolitinib cream 1.5% BID significantly increased the F-VASI75 response rate at 24 weeks compared to vehicle. The updated report included ruxolitinib-treated patients who continued on the JAK inhibitor through week 52, as well as placebo-treated patients who crossed over to ruxolitinib after completing the 24-week randomized trial.
The two trials included a combined total of 674 patients aged 12 years and older with nonsegmental vitiligo. They were randomized 2:1 to receive topical ruxolitinib or vehicle, and the primary outcomes were F-VASI75, F-VASI50, F-VASI90, T-VASI50, and an assessment of the Vitiligo Notability Scale ( VNS) from “much less noticeable” or “more 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 treatment. ruxolitinib. In TRuE-V2, F-VASI75 response rates decreased from 30.9% and 11.4% at 24 weeks with ruxolitinib and placebo, respectively, to 48.0% and 29.6% at 52 weeks.
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% in patients who crossed over 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 substitution group.
Three-quarters of patients on continuous ruxolitinib had F-VASI50 responses at week 52 in both trials, as did more than half of patients initially assigned to placebo and then switched to ruxolitinib. Half of the patients in both trials met truncal response criteria (T-VASI50) at week 52, just as 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, compared to 15-20% of patients initially assigned 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 effectiveness in active versus stable lesions, as Yamaguchi reported in a poster presentation at AAD.
The analysis included 364 patients randomized to receive placebo or one of five ritlecitinib dosage groups: 10 mg, 30 mg, 50 mg and 50 mg with loading doses of 200 mg or 100 mg. The results showed that the 50 mg dose (with or without a loading dose) and the 30 mg dose significantly reduced depigmentation compared to placebo in active lesions (P=0.0096 to P=0.0090).
In stable lesions, statistically significant repigmentation occurred with all doses of ritlecitinib except the 10 mg dose, whereas placebo was not associated with any change in lesion status (P=0.0016 to P=0.0090).
In a separate presentation, Yamaguchi reported an analysis of efficacy for different doses of ritlecitinib by Fitzpatrick skin types, including patients who completed a 24-week extension phase. The study involved a total of 247 patients with Fitzpatrick skin type I-III and 117 patients with type IV-VI. Data from patients assigned to the 50 mg and lower dose regimens have been pooled separately.
At the end of the 24-week dosing period, Fitzpatrick I-III patients treated with 50 mg ritlecitinib showed a 15.2% reduction in F-VASI compared to placebo (P=0.0043), and patients treated with the lower doses had a 5.5% reduction (P=0.1991). Patients with Fitzpatrick IV-VI showed 37.4% improvement and 15.7% improvement with ritlecitinib compared to placebo (PP
After an extension period of 24 weeks, patients treated continuously with ritlecitinib showed an improvement in F-VASI of 51-63% compared to placebo for patients with Fitzpatrick I-III and differences of 51-68 % for Fitzpatrick IV-VI.
“Continued repigmentation with no efficacy plateau was observed at week 48 in Fitzpatrick I-III and IV-VI skin types,” Yamaguchi said.
The ruxolitinib study was supported by Incyte.
Rosmarin disclosed relationships with Abcuro, AltruBio, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert Pharmaceuticals, Dermavant Sciences, Incyte, Janssen Biotech, Kyowa Hakko Kirin Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceutical, UCB and Viela Bio.
The ritlecitinib studies were supported by Pfizer.