1. In comparison to vehicle-control, a greater proportion of patients using ruxolitinib achieved a reduction in facial Vitiligo Area Scoring Index (F-VASI) of at least 75% at 24 weeks.

2. Significantly more patients using ruxolitinib achieved a reduction in total Vitiligo Area Scoring Index (T-VASI) of at least 50% at 24 weeks as compared to vehicle-control.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Non-segmental vitiligo is a skin condition that results in distinct lesions of the skin, mucosa, and hair which become depigmented over time. Vitiligo is thought to be autoimmune in its origin and is associated with reduced quality of life for patients affected. Janus kinase 1 (JAK1) and 2 (JAK2) inhibitors are signal transducers that aim to reduce skin lesion depigmentation in vitiligo by inhibiting associated signaling pathways. Ruxolitinib is a JAK1 and JAK2 inhibitor which has shown promising results in reducing depigmentation during phase two trials. This study was a phase three double-blind trial investigating the efficacy of ruxolitinib cream for patients 12 years and older with non-segmental vitiligo at 24 weeks, with an additional open-label extension of up to 54 weeks. It primarily aimed to understand whether there was a difference in body surface-area depigmentation with ruxolitinib in comparison to a vehicle-control cream at 24 weeks. Results found that ruxolitinib caused a greater improvement in vitiligo depigmentation than vehicle control. Although this study demonstrated promising results in favor of ruxolitinib in the treatment of vitiligo, it is limited by its loss-to-follow-up, participation discontinuation, and lack of intention-to-treat analysis. It is further limited by its duration of follow-up which precludes conclusions of its long-term safety profile and efficacy. Although further investigation is required, this study provided evidence of ruxolitinib as a promising agent to improve skin lesion depigmentation which can achieve improved outcomes than vehicle-control amongst adolescents and adults with vitiligo.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: This study consists of two multinational, phase three, double-blind trials (TRuE-V1 and TRuE-V2) evaluating the efficacy of topical 1.5% ruxolitinib in non-segmental vitiligo with mild face and total body depigmentation compared against vehicle control. All patients 12 years of age or older with an F-VASI score of 0.5 or greater and a T-VASI score of three or higher were included. Patients with depigmentation covering more than 10% of their total body surface area were excluded. In total, 674 patients across two trials were assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream twice daily (n=450) or a matched vehicle control cream (n=224) twice daily to depigmented areas over a period of 24 weeks. The primary outcome of interest was a decrease in F-VASI of at least 75% at 24 weeks. Secondary outcomes of interest included a decrease in F-VASI at 24 weeks of at least 50% and 90%, a decrease in T-VASI response at 24 weeks of at least 50%, a decrease in the Vitiligo Noticeability Scale, and a percentage change in the facial surface area affected. Results of the primary analysis found that ruxolitinib was more likely to cause a decrease in F-VASI of at least 75% than the vehicle control (relative risk, 4.0; 95% Confidence Interval [CI], 1.9-8.4; p<0.001). Results of secondary outcomes found that ruxolitinib was more likely than the control to cause a decrease in F-VASI of at least 50% (p<0.001) and at least 90% (p=0.004). Ruxolitinib caused a reduction in T-VASI of at least 50% than control in both trials (p=0.002 and p<0.001 for TRuE-V1 and TRuE-V2, respectively). Similar results were found for results comparing the Vitiligo Noticeability Scale and the percent change in the facial surface area affected. Overall, this study demonstrates that ruxolitinib has a greater ability to increase the proportion of repigmentation in non-segmental vitiligo than vehicle-control. However, trials investigating the use of ruxolitinib in vitiligo with longer duration of follow-up and in populations with greater skin pigmentation (coloring) are required to ascertain the long-term safety profile, sustained efficacy, and optimal dosing regimen.

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