Vunakizumab Efficacy Across Baseline Duration and Severity in Psoriasis

Key Takeaways

• At week 12, PASI 75, PASI 90, PASI 100, and sPGA 0/1 responses were higher with vunakizumab than placebo across psoriasis duration, PASI, BSA, and sPGA strata.
• The same general pattern was seen at weeks 4 and 8, while week 24 generally favored continuous vunakizumab over patients who switched from placebo at week 12.

In a phase III post hoc analysis of moderate-to-severe plaque psoriasis, week 12 subgroup comparisons across duration and severity strata favored vunakizumab over placebo, with all reported p values below 0.001. Response patterns were examined across baseline strata defined by psoriasis duration, PASI score, body surface area involvement, or sPGA score. By week 52, separation between continuous vunakizumab and delayed initiation after placebo crossover had narrowed substantially.

This post hoc analysis used data from a randomized, double-blind, placebo-controlled trial in 690 patients with moderate-to-severe plaque psoriasis. Participants were randomized 2:1 to vunakizumab 240 mg or placebo, with 461 assigned to vunakizumab and 229 to placebo. Initial dosing occurred at weeks 0, 2, 4, and 8, then placebo switched at week 12 and received doses at weeks 14 and 16 and every 4 weeks thereafter, while continuous vunakizumab continued every 4 weeks through week 52. Subgroups were defined by psoriasis duration under 2 years versus 2 years or longer, baseline PASI under 20 versus 20 or higher, BSA under 20% versus 20% or higher, and sPGA under 4 versus 4 or higher.

At week 12, response rates for PASI 75, PASI 90, PASI 100, and sPGA 0/1 were higher with vunakizumab than placebo across all reported duration, PASI, BSA, and sPGA strata, with all comparisons reported as p<0.001. Earlier assessments at weeks 4 and 8 also favored vunakizumab across the same baseline categories, with significance levels of p<0.05 or p<0.001 depending on endpoint and subgroup. At week 24, after placebo crossover at week 12, the general directional pattern still favored continuous vunakizumab across the same strata, although not every endpoint differed in every subgroup.

By week 52, differences between continuous vunakizumab and delayed initiation after placebo crossover were almost substantially attenuated. The authors attributed that attenuation in part to the week 12 crossover from placebo to active treatment. Limited residual differences remained in some subgroups, including higher PASI 75 in duration subgroups, in PASI under 20, and in BSA 20% or higher, plus higher sPGA 0/1 in duration under 2 years and higher PASI 75, PASI 90, and sPGA 0/1 in sPGA under 4.