AB0544 EFFICACY AND SAFETY OF TILDRAKIZUMAB IN PATIENTS WITH AND WITHOUT METABOLIC SYNDROME: 5-YEAR POOLED DATA FROM reSURFACE 1 AND reSURFACE 2
Authors: A. B. Gottlieb, N. Mehta, A. Menter, A. M. Mendelsohn, S. Rozzo, M. Lebwohl
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with psoriasis and metabolic syndrome (MetS) may have reduced absolute Psoriasis Area and Severity Index (PASI) response and long-term drug survival. Tildrakizumab is approved for the treatment of moderate to severe plaque psoriasis in the US, EU, Australia, and Japan. Efficacy and safety of tildrakizumab were previously shown to be comparable in patients with vs without MetS after 1 and 3 years of treatment. 1 Objectives: This post hoc analysis of pooled data from reSURFACE 1 and reSURFACE 2 ( NCT01722331 /NCT01729754) assessed tildrakizumab efficacy and safety through up to 5 years of treatment in patients with psoriasis with and without MetS. Methods: reSURFACE 1 and 2 were 3-part, double-blind, randomized controlled phase 3 trials with long-term extensions evaluating tildrakizumab 100 or 200 mg monotherapy at Weeks 0, 4, and every 12 weeks thereafter in adults with moderate to severe plaque psoriasis. 2 Patients who achieved ≥50% improvement from baseline PASI score (PASI 50 response) at both week 28 and at the end of the phase 3 studies could enter the long-term extension studies continuing the same dose of tildrakizumab. 1 This post hoc analysis reports results from a pooled data analysis through up to 5 years of tildrakizumab exposure from patients with and without MetS by National Cholesterol Education Program-Adult Treatment Panel III criteria who continuously received the same dose of tildrakizumab throughout the base studies and entered the long-term extensions. Efficacy was assessed as change from baseline PASI score; missing data were handled using multiple imputation. Safety was assessed from exposure adjusted incidence rates of serious adverse events (SAEs) and treatment-emergent AEs of special interest. Results: Analyses included 70/265 patients with/without MetS receiving tildrakizumab 100 mg and 64/241 patients with/without MetS receiving tildrakizumab 200 mg. Median percentage change from baseline PASI score is shown in Figure 1. Among patients with/without MetS receiving tildrakizumab 100 mg, 78.6%/87.9% achieved PASI 75, 57.1%/63.8% achieved PASI 90, and 25.7%/32.5% achieved PASI 100 response at week 244; the PASI 75, PASI 90, and PASI 100 response rates at week 244 in patients with/without MetS receiving tildrakizumab 200 mg were 76.6%/85.1%, 46.9%/61.4%, and 26.6%/36.5%, respectively. Safety outcomes over the 5-year extension period were consistent with the known safety profile of tildrakizumab. Rates of SAEs were &lt;8.5 per 100 patient-years among all patients, and there were no new safety signals in patients with vs without MetS (Table 1). Table 1. SAEs and TEAEs of special interest by MetS status through up to 5 years of tildrakizumab exposure TIL 100 mg TIL 200 mg Without MetS With MetS Without MetS With MetS n = 265 n = 70 n = 241 n = 64 n (EAIR per 100 PY ) 1149.1 PY 304.1 PY 1057.1 PY 287.6 PY SAEs 53 (4.61) 22 (7.23) 52 (4.92) 24 (8.35) TEAEs of special interest 24 (2.09) 6 (1.97) 27 (2.55) 15 (5.22) Infections and infestations 10 (0.87) 2 (0.66) 13 (1.23) 6 (2.09) Malignancies a 5 (0.44) 1 (0.33) 4 (0.38) 3 (1.04) Nonmelanoma skin cancer 3 (0.26) 1 (0.33) 6 (0.57) 1 (0.35) Confirmed extended MACE 3 (0.26) 1 (0.33) 3 (0.28) 3 (1.04) Drug hypersensitivity 2 (0.17) 1 (0.33) 1 (0.09) 2 (0.70) Melanoma skin cancer 2 (0.17) 0 0 0 Injection site reactions b 1 (0.09) 0 0 0 Incidence rates reported as events per 100 PY. a Excluding nonmelanoma and melanoma skin cancer. b Not considered of special interest in the extension study. AE, adverse event; EAIR, exposure adjusted incidence rate; MACE, major adverse cardiovascular events; MetS, metabolic syndrome; PY, patient-years; SAE, serious AE; TEAE, treatment-emergent AE; TIL, tildrakizumab. Conclusion: The efficacy and safety of tildrakizumab were maintained in patients with and without MetS following 5 years of treatment. References: [1]Lebwohl, M et al. JAAD . 2020;S0190-9622(20)32637-2. [2]Reich K, et al. Lancet. 2017;390:276–88. Disclosure of Interests: Alice B Gottlieb Shareholder of: Xbiotech (only stock options, which she has not used)., Consultant of: Anaptyps Bio, Avotres Therapeutics; Beiersdorf; Boehringer Ingelheim; Bristol-Myers Squibb Co.; Eli Lilly; Janssen; LEO Pharma; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech, Grant/research support from: Boehringer Ingelheim; Janssen; Novartis; Sun Pharmaceutical Industries, Inc.; UCB; and Xbiotech., Nehal Mehta Grant/research support from: Grants to the NIH from AbbVie, Celgene, Janssen, and Novartis., Employee of: Full-time employee of the US government., Alan Menter Speakers bureau: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck &amp; Co., Novartis, Sienna, and UCB., Consultant of: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck &amp; Co., Novartis, Sienna, and UCB., Grant/research support from: AbbVie, Abbott Labs, Amgen, Anacor, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, LEO Pharma, Merck &amp; Co., Novartis, Sienna, and UCB., Alan M Mendelsohn Shareholder of: Has individual shares in Johnson and Johnson, and as part of retirement account/mutual funds, Employee of: Sun Pharmaceutical Industries, Inc., Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc., Mark Lebwohl Consultant of: Aditum Bio; Allergan; Almirall; Arcutis; Avotres Therapeutics; BirchBioMed, Inc.; BMD Skincare; Boehringer Ingelheim; Bristol-Myers Squibb; Cara Therapeutics; Castle Biosciences; Corrona; Dermavant Sciences; Evelo; Facilitate International Dermatologic Education; Foundation for Research and Education in Dermatology; Inozyme Pharma; Kyowa Kirin; LEO Pharma; Meiji Seika Pharma; Menlo; Mitsubishi; Neuroderm; Pfizer; Promius/Dr. Reddy’s Laboratories; Serono; Theravance; and Verrica., Grant/research support from: AbbVie; Amgen; Arcutis; Boehringer Ingelheim; Dermavant; Eli Lilly; Incyte; Janssen Research &amp; Development, LLC; LEO Pharma; Ortho Dermatologics; Pfizer; and UCB.