NEJM: Results of phase III clinical studies of ruxotinib in vitiligo are promising

Vitiligo is a chronic autoimmune disease that causes white patches of skin due to loss of melanocyte function
.
It was found that interferon-γ plays an important role in the pathogenesis and signaling of vitiligo through the Janus kinase (JAK) signal transducer and transcriptional activator (STAT) pathway, which can lead to upregulation of C-X-C motif chemokine ligand 10 (CXCL10), promote the recruitment of CD8+ T cells, and drive the destruction
of melanocytes.
In a previous phase II trial in adult vitiligo patients, the Janus kinase 1 and 2 inhibitor ruxotinib promoted lesion repigmentation
in vitiligo patients.
Researchers recently announced the phase III clinical results
of ruxotinib in the treatment of vitiligo.

The TRuE-V1 and TRuE-V2 studies were conducted in North America and Europe in patients over 12 years of age with nonsegmental (vulgar) vitiligo, with no more than 10%
of the skin lesions depigmented.
Ruxotinib 1.
5% ruxotinib cream or control was randomly applied twice daily to all vitiligo areas of the face and body for 24 weeks, after which all patients received 1.
5% ruxotinib cream until week
52.
The primary endpoint of the study was a 75% improvement in the severity index of facial vitiligo (F-VASI, 0-3, the higher the score, the more severe the symptoms) compared with baseline≥ (F-VASI 75).

There were 5 secondary endpoints, including improvement
on the Leukoplakia Significance Scale (VNS).

A total of 674 patients participated in the study
.
In the TRuE-V1 study, the 24-week response rate of F-VASI75 was 29.
8% in the ruxotinib group and 7.
4% in the control group (rr=4.
0).

In the TRuE-V2 study, the 24-week response rate of F-VASI75 was 30.
9% in the ruxotinib group and 11.
4% in the control group (rr=2.
7).

For secondary outcomes, the ruxotinib group had an advantage.

Among patients who completed 52 weeks of treatment, the adverse event rate was 54.
8% in the TRuE-V1 study and 62.
% in the TRuE-V2 study, and the most common adverse events were smear-site acne (6.
3% and 6.
6%), nasopharyngitis (5.
4% and 6.
1%), and pruritus at the smear site (5.
4% and 5.
3%)
.

Phase III clinical studies have demonstrated that ruxotinib significantly improves skin lesion repigmentation in vitiligo patients, but has an increased risk of acne and pruritus.

Original source:

David Rosmarin et al.
Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo，N Engl J Med，October 20, 2022.