Ritlecitinib is a JAK3/TEC family kinase–targeted inhibitor that halts vitiligo pathogenesis.In two pivotal phase III Tranquillo studies, individuals with nonsegmental vitiligo (NSV) achieved significant and clinically meaningful improvements in facial and total body repigmentation after 52 weeks of treatment with oral ritlecitinib.
“The improvements in facial and total body repigmentation were observed by week 24 and increased through week 52. The responses continued to increase through week 52 without plateau, supporting the sustained efficacy of ritlecitinib over time,” said Dr Iltefat Hamzavi from Hamzavi Dermatology Specialists, Detroit, Michigan, US, at EADV 2026.
In Tranquillo 2 Part Ia, 1,036 patients were randomized 3:1:1 to ritlecitinib 100 mg (R100), ritlecitinib 50 mg (R50), or placebo QD for 52 weeks. In Tranquillo, 603 participants were randomized 2:1 to R50 or placebo QD for 52 weeks. [EADV 2026, abstract 161]
Overall, approximately 53 percent of the participants were women, about one-quarter were Asian, and the mean age was 46 years. Approximately two-thirds had Fitzpatrick skin types III and IV. The mean disease duration since onset was approximately 16 years.
Compared with the placebo group, the ritlecitinib groups in both Tranquillo 2 (R100) and Tranquillo (R50) had a significantly higher proportion of participants who achieved F-VASI75* at week 52 (21.86 percent vs 2.4 percent and 12.47 percent vs 2.48 percent, respectively). The same held true for T-VASI50** (13.02 percent vs 2.4 percent and 8.98 percent vs 1.98 percent; p<0.0001 for all).
“There were greater mean percentage reductions from baseline in F-VASI and T-VASI with ritlecitinib vs placebo, with significant differences seen as early as week 12 in both trials,” Hamzavi added.
Patient-reported outcomes
At week 52, more R100 than placebo recipients in Tranquillo 2 achieved PGIS−F*** (42.9 percent vs 18.3 percent; p<0.01) and PGIS–V*** responses (32.3 percent vs 17.3 percent; p<0.01). A similar pattern favouring R50 was observed in Tranquillo (35 percent vs 12.2 percent; p<0.01 and 23.3 percent vs 16.6 percent; p<0.05, respectively).
There were also meaningful improvements in PGIC–F# and PGIC–V# with ritlecitinib vs placebo at week 52 in both Tranquillo trials (p<0.05 for all).
Approximately 20 percent of R100 recipients in Tranquillo 2 reported their vitiligo was significantly less noticeable; only 1 percent did in the placebo group (p<0.05). The corresponding proportions in Tranquillo were 12 percent and 4.5 percent (p<0.05).
“[Taken together, these patient-reported outcomes] indicate reduced perceptions of disease severity, meaningful changes in facial and total body vitiligo, and less noticeable lesions,” Hamzavi explained.
Disease stabilization, safety
In both studies, more participants receiving ritlecitinib than placebo achieved disease stabilization through 52 (Tranquillo 2: 76.5 percent vs 60.1 percent; Tranquillo: 74.8 percent vs 59.4 percent; p<0.01 for both). Of note, more placebo recipients had disease progression after week 8.
“These results support ritlecitinib’s mechanism of action as a JAK3/TEC## family kinase–targeted inhibitor that halts vitiligo pathogenesis,” Hamzavi said.
Most treatment-emergent adverse events (TEAEs) in both studies were nonserious and the incidences of serious and severe TEAEs were comparable, as were the TEAEs of special interest. The most common TEAE in both groups was upper respiratory tract infection.
Taken together, the findings support those reported in a phase IIb study demonstrating the efficacy and tolerability of ritlecitinib in adults with active NSV over 48 weeks. [J Am Acad Dermatol 2023;88:395-403]