NEW YORK CITY -- Almost 30% of patients with vitiligo had at least 75% improvement in facial involvement after 6 months of treatment with a topical formulation of the Janus kinase (JAK) inhibitor ruxolitinib (Opzelura), two randomized trials showed.
The vehicle-controlled trials yielded identical primary-outcome results, as 29.9% of ruxolitinib-treated patients in each trial met criteria for 75% improvement on the facial Vitiligo Area and Scoring Index (F-VASI75). Half the patients in each trial had at at least 50% improvement at 6 months (F-VASI50).
The topical treatment was well tolerated, as adverse events (AEs) consisted mostly of application-site reactions, such as acne and pruritus, said David Rosmarin, MD, of Tufts Medical Center in Boston, at the Inflammatory Skin Diseases Summit.
"Ruxolitinib cream monotherapy demonstrated clinically meaningful superiority to vehicle for the primary and all key secondary endpoints in two phase III studies," said Rosmarin. "There was substantial facial and total body repigmentation evident at 24 weeks, confirming the phase II findings. Ruxolitinib cream was well tolerated and no serious treatment-related AEs were reported."
"As we know that repigmentation can take time, I particularly look forward to the 52-week results, which will hopefully show even improvement responses from the week 24 results," he added.
The rationale for treating vitiligo with a JAK inhibitor evolved from recognition that the disease's pathogenesis is regulated primarily by interferon-gamma activation of the JAK signaling pathway. A phase II trial of ruxolitinib cream for vitiligo demonstrated substantial repigmentation at 52 weeks, supporting phase III investigation.
The parallel TRuE-V1 and TRuE-V2 trials involved adolescents (ages ≥12) and adults with vitiligo, randomized 2:1 to the 1.5% ruxolitinib cream or vehicle, applied twice daily for 24 weeks. Patients who completed the double-blind phase of the trial were eligible to participate in a 28-week extension, wherein all patients received topical ruxolitinib. The primary endpoint was the proportion of patients who attained F-VASI75 at the end of randomized treatment.
Eligible patients had ≤10% total body surface area (BSA), ≥0.5% total BSA on the face, ≥3% total BSA on nonfacial areas, F-VASI score ≥0.5, and T-VASI ≥3. Patients with complete leukotrichia within any facial lesion were ineligible, as were patients with a history of JAK inhibitor therapy.
Data analysis included 330 patients from TRuE-V1 and 344 from TRuE-V2, women accounted for 53% of the study population, and whites made up more than 80% of the population. Mean baseline F-VASI was about 0.9, T-VASI of about 6.5, F-BSA of about 1, T-BSA of about 7.3, and disease duration of about 12 years. Most of the patients had received prior therapy, most often topical calcineurin inhibitors, topical steroids, and phototherapy.
The 24-week results showed a 22.5% absolute difference from vehicle in TRuE-V1 (P<0.0001) and 16.9% in TRuE-V2 (P<0.01). Ruxolitinib-treated patients also had statistically significant advantages for F-VASI50 (51.5% vs 17.2% and 51.4% vs 23.4%, P<0.0001 for both comparisons) and F-VASI90 (15.5% vs 2.2%, P<0.01; 15.4% vs 1.9%, P<0.05).
The rate of T-VASI50 response at 24 weeks was 20.6% versus 4.9% in TRuE-V1 and 26.1% versus 11.3% in TRuE-V2 (P<0.01). Additionally, 24.5% and 21.9% of patients in TRuE-V1 and TRuE-V2, respectively, achieved Vitiligo Noticeability Scale responses ("at lot less" or "no longer" noticeable) as compared with 3.3% and 6.6% of vehicle-treated patients (P<0.001; P<0.01). Changes in F-BSA at week were -28.8% and -16.3% with ruxolitinib versus -9.5% and +2.3% with vehicle (P<0.0001; P<0.05).
With regard to safety, application-site acne occurred in about 6% of patients treated with ruxolitinib cream and about 5% developed application site pruritus. Other AEs (15-5% of patients) included nasopharyngitis, headache, and upper respiratory tract infection. One ruxolitinib-treated patient discontinued treatment because of AEs in each trial.
Rosmarin said the plasma concentration for JAK2-mediated changes in bone marrow was below the half-maximal inhibitor concentration. No clinically significant changes in hemoglobin or platelet values occurred during randomized treatment.
In response to an attendee question, Rosmarin said ruxolitinib cream was applied to a maximum of 10% total BSA in the phase III trials and a maximum BSA of 20% in the phase II trial.
The TRuE-V trials were supported by Incyte.
Rosmarin disclosed relationships with AbbVie, Abcuro, AltruBio, Boehringer Ingelheim, Bristol Myers Squib, Celgene, Concert, Dermavant Sciences, Dermira, Incyte, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, VielaBio, Amgen, Bristol Myers Squibb, Galderma, and Merck.