Tildrakizumab Shows Sustained Efficacy, Safety Over a 5-Year Period for Moderate to Severe Plaque Psoriasis Advances

Tildrakizumab, an IL-23 inhibitor, demonstrated positive 5-year data from two phase 3 extension studies on the treatment of moderate to severe plaque psoriasis.¹ Patients who continued to receive tildrakizumab through 5 years of continuous treatment had sustained skin clearance, with no new safety issues noted.

The biologic agent is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23, preventing the release of proinflammatory cytokines and chemokines. Tildrakizumab is approved for the treatment of plaque psoriasis in the United States as well as Europe, Australia, and Japan.

The phase 3 studies, reSURFACE 1 and reSURFACE 2, were randomized, placebo-controlled, multicenter, three-part studies to evaluate the efficacy, tolerability, and safety of tildrakizumab 100 and 200 mg vs placebo and a comparative drug for the treatment of moderate to severe plaque psoriasis. Patients who completed the base study with at least 50% improvement in Psoriasis Area and Severity Index (PASI) and who received tildrakizumab within 12 weeks of base study end were eligible to enroll in the extension study. Patients were continued on the same tildrakizumab dose or placebo once every 12 weeks.  PASI and Physician Global Assessment response (score of 0 or 1 with ≥2 grade reduction from baseline) and incidence rates for prespecified adverse events (AEs; severe infections, cardiovascular events, drug-related hypersensitives) were recorded.

Upon analysis of the pooled extension studies, PASI 75 was achieved by 88.7% of patients at week 244. Further, 65.9% and 32.8% of patients who received tildrakizumab 100 mg achieved PASI 90 and PASI 100, respectively, in the same time frame. Long-term analyses demonstrated absolute PASI scores of less than 1, 3, and 5 at week 28 were sustained through study completion (week 244).

For patients receiving tildrakizumab 100 mg, the three AEs that occurred more frequently than placebo and at least 1% or more in clinical trials were upper respiratory infections (14% vs 12%), injection site reactions (3% vs 2%), and diarrhea (2% vs 1%). In addition, there was a similar exposure-adjusted incidence rate of malignancies throughout the 5-year study. Most malignancies were singular events with similar incidence rates as the general US population. Further analyses of the prespecified AEs were shared at the American Academy of Dermatology Virtual Meeting Experience 2021.^2-5

References
1. Sun Pharma announces 5-year sustained efficacy and safety results for ILUMYA® (tildrakizumab-asmn) in patients with moderate-to-severe plaque psoriasis. News release. Sun Pharma. October 31, 2020. Accessed June 4, 2021. https://www.prnewswire.com/news-releases/sun-pharma-announces-5-year-sustained-efficacy-and-safety-results-for-ilumya-tildrakizumab-asmn-in-patients-with-moderate-to-severe-plaque-psoriasis-301164297.html

2. Trickett C, Gniadecki R, West DT, Mendelsohn AM, Rozzo SJ, Dhawan S. Rates of individual and composite cardiovascular events through 5 years of tildrakizumab exposure in 2 phase 3 clinical trials. Poster presented at: American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021; virtual.

3. Friedman A, Vender RB, Desaai M, Mendelsohn AM, Rozzo SJ, Cather J. Malignancies related to study drug and leading to discontinuation through 5 years of tildrakizumab exposure in 2 phase 3 clinical trials. Poster presented at: American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021; virtual.

4. Gebauer K, Song EJ, Mendelsohn AM, Rozzo SJ, Kivelevitch D. Serious infections and infections related to study drug and leading to discontinuation through 5 years of tildrakizumab exposure in 2 phase 3 clinical trials. Poster presented at: American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021; virtual.

5. Conner J, Elewski BE, Baum-Jonens A, Mendelsohn AM, Rozzo SJ, Gooderhaam M. Gastrointestinal adverse events related to study drug and leading to discontinuation through 5 years of tildrakizumab exposure in 2 phase 3 clinical trials. Poster presented at: American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021; virtual.