SAT0110 Efficacy and Safety of Pateclizumab (Anti-Lymphotoxin-Alpha) in Dmard-Ir Patients: Results of a Randomized, Double-Blind, Placebo-Controlled Head-To-Head Phase 2 Study with Adalimumab

Background Pateclizumab (formerly MLTA3698A), a novel humanized IgG1 antibody against soluble and membrane isoforms of lymphotoxin-alpha, is being investigated as a targeted therapy for rheumatoid arthritis (RA). Objectives To compare the efficacy and safety of subcutaneous Pateclizumab (PTZ) vs placebo (PBO) and adalimumab (ADA) in patients with active RA and an inadequate response to DMARDs. Methods RA patients on oral DMARDs were randomized (2:2:1) to receive PTZ 360 mg, ADA 40 mg, or PBO every 2 weeks. The primary endpoint, DAS28-ESR, was evaluated at 12 weeks. Pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PTZ were assessed. Results 217 patients were enrolled, 85 received PTZ, 85 received ADA, and 44 received PBO. Baseline demographics [mean (±SD)], age 50 years (±13.3), disease duration 8.7 yrs (±8.1), and clinical characteristics, were balanced across treatment arms. Mean baseline characteristics included a SJC of 18.6/17.4/15.8, TJC of 28.6/28.1/23.2, HAQ scores of 1.8/1.7/1.8, CRP values of 2.2/2.2/2.4 mg/dL, and DAS28-ESR scores of 6.95/6.82/6.79, for PTZ/ADA/PBO, respectively. RF/anti-CCP status and use of methotrexate or leflunomide as DMARD agent were comparable across groups at baseline. 86% of PTZ, 87% of ADA, and 77% of PBO subjects completed 10 weeks of dosing for the efficacy analyses. PTZ 12wk DAS28-ESR response (-1.96) was not significantly different from PBO (-1.66), while ADA (-2.63) differed significantly from both PBO (P