Long-term Efficacy Observed in Patients with PsO Receiving Tildrakizumab

Howard Sofen, MD

Credit: Credit: DrSofen.com

Patients with moderate to severe scalp psoriasis treated with tildrakizumab demonstrated maintained efficacy through week 52, with no new safety signals reported through week 72, according to data presented at the 2023 Fall Clinical Dermatology Conference.¹

The safety and efficacy of the drug, an anti-interleukin-23 p19 monoclonal antibody, was assessed in a phase 3b, double-blind, placebo-controlled study enrolling adult patients with moderate to severe plaque psoriasis. Disease severity was defined as a Psoriasis Scalp Severity Index (PSS) ≥12, ≥30% scalp surface area affected, and scalp-specific version of the Investigator Global Assessment (IGA) ≥3. The primary endpoint was the modified IGA of the scalp response, which was defined as either 0 (clear) or 1 (almost clear) with a ≥2-point reduction from baseline at week 16.

In the first part of the trial, subjects were randomized 1:1 to receive either tildrakizumab 100 mg or placebo at week 0 and week 4. Following these initial doses, patients in the tildrakizumab group continued to receive the drug at week 16 and every 12 weeks through week 52, while patients receiving the placebo were switched to tildrakizumab 100 mg at weeks 16, 20, 32, and 44. Patients were then eligible to participate in a 20-week observational, treatment-free, safety follow-up period to determine the safety and tolerability of the drug through week 72.

Efficacy at various endpoints throughout the study was determined using the 5-point IGA modification. Additionally, the proportions of patients at the 16-week mark who were able to achieve a ≥90% reduction from baseline in PSSI (PSSI 90) and IGA mod 2011 (scalp) were evaluated at week 52. Treatment-emergent adverse events (TEAEs) were reported through week 72.

A total of 231 patients received treatment and 171 were included in the modified intention-to-treat (mITT) cohort. Most patients in this group were White (78.9%) and male (60.2%), with a mean age of 44.8 years. According to the IGA mod 2011 scale, most patients in the mITT cohort had moderate disease burden at baseline.

At week 16, the primary endpoint of scalp IGA response with a ≥2-point reduction was met in patients receiving tildrakizumab, with the proportion of responders continuing to respond from 49.4% at week 16 to 62.9% at week 52. Most (81.8%, n = 36/44) patients achieving week 16 response maintained responses at week 52. Regarding PSSI 90, 60.7% achieved response at week 16, compared with only 4.9% of patients in the placebo cohort. In responders, 81.5% treated with the drug were able to maintain PSSI 90 response at week 52.

Most TEAEs were categorized as mild to moderate in severity and the proportion of patients reporting ≥1 TEAE was similar across treatment groups. Adverse events (AEs) of interest were reported in 5 patients, 4 of which experienced cardiac events unrelated to treatment and 1 patient had a macular rash. Serious AEs were reported in 6 patients during parts 2 and 3 of the trial, none of which were considered to be treatment-related. The most common TEAEs during this time were upper respiratory tract infection and low-density lipoprotein increase in the original tildrakizumab cohort, and fungal skin infection, impaired fasting glucose, viral rhinitis, hand dermatitis, vulvovaginal candidiasis, and macular rash in patients switching to tildrakizumab from placebo. However, no treatment-related serious AEs, prespecified AEs of interest, or deaths were reported during the study period.

References

1. ^{Sofen H, Gebauer K, Spelman L, Yamauchi PS, et al. Efficacy and safety of tildrakizumab for the treatment of moderate to severe plaque psoriasis of the scalp: Week 52 results from a Phase 3b, randomized, double-blind, placebo-controlled trial. Presented at: Fall Clinical Dermatology 2023 Conference. Las Vegas, NV. October 19 – 22, 2023.}