Phase 3 trials show upadacitinib improves repigmentation in nonsegmental vitiligo
Two phase 3 trials found upadacitinib 15 mg significantly improved facial and total repigmentation versus placebo at 48 weeks in nonsegmental vitiligo. The 614-patient studies also showed continued improvement over time and a safety profile consistent with prior use.
Upadacitinib 15 mg produced statistically significant, progressively improving repigmentation in adolescents and adults with nonsegmental vitiligo through 48 weeks in two global phase 3 trials. The co-primary end points were met with statistical significance in both studies, and all participants were then assigned to a 112-week open-label extension.
The Viti-Up-1 and Viti-Up-2 trials enrolled participants 12 years or older with nonsegmental vitiligo affecting the face and body, with a F-VASI score of 0.5 or more at baseline and a T-VASI score of 5 or more. The studies enrolled 308 people in Viti-Up-1 and 306 in Viti-Up-2, for a total of 614 people from 18 countries. Participants were randomly assigned 2:1 to receive 15 mg of oral upadacitinib or placebo once daily, and they did not receive phototherapy or any other treatments.
In Viti-Up-1, T-VASI 50 was achieved by 19.4% of patients treated with upadacitinib vs 5.9% on placebo, and F-VASI 75 by 25.2% of patients treated with upadacitinib vs 5.9%. In Viti-Up-2, T-VASI 50 was achieved by 21.5% of patients treated with upadacitinib vs 5.9% on placebo, and F-VASI 75 by 23.4% of patients treated with upadacitinib vs 6.9%; both primary end points were significant at P ≤0.001.
Treatment also was superior to placebo on the Vitiligo Noticeability Scale. In Viti-Up-1, 12.6% of the treatment group scored 4 or 5 on the VNS compared with 2.0% of the placebo group; in Viti-Up-2, 14.6% of treated patients scored a 4 or 5, vs 1.0% of those in the placebo group. Multiple secondary endpoints were also significantly improved among those treated vs placebo, including F-VASI 50 at week 48, F-VASI 75 at week 24, F-VASI 90 at week 48, percent change from baseline in F-VASI at week 24, percent change from baseline in T-VASI at week 48, and physician and patient global impression of change at week 48.
Responses continued to build throughout the observation period with no sign of leveling off. Secondary end points further showed that F-VASI 50 at week 48 was achieved by approximately 48% of patients treated with upadacitinib across both trials, and roughly 12% to 15% achieved the more stringent F-VASI 90 threshold.
Among patients with actively progressing vitiligo at baseline, defined by confetti-like depigmentation, koebnerization, or trichrome vitiligo, approximately 76% of patients treated with upadacitinib showed no increase in T-VASI at weeks 8 and 12, compared with roughly 61% on placebo, with p=0.025 in Viti-Up-1 and p=0.042 in Viti-Up-2.
Safety findings through 48 weeks were consistent with the established profile for upadacitinib across its other dermatologic and rheumatologic indications. The most commonly reported treatment-emergent adverse events included upper respiratory tract infection, acne, nasopharyngitis, and headache. There were no cases of adjudicated major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, active tuberculosis, lymphoma, or non-melanoma skin cancer in either study, while herpes zoster was reported in a small number of patients treated with upadacitinib across both trials.
Upadacitinib 15 mg daily also was described as demonstrating promising repigmentation in phase 3 studies of extensive nonsegmental vitiligo. The trials included a severe population: about 60% had active vitiligo at study entry, more than three fourths had more than 10% of their body surface area affected, and the mean time since diagnosis ranged from 15.6 to 16.7 years.