Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

OBJECTIVE: To investigate the safety and efficacy of ABT‐122, a tumor necrosis factor (TNF)– and interleukin‐17A (IL‐17A)–targeted dual variable domain immunoglobulin, in patients with active psoriatic arthritis (PsA) who have experienced an inadequate response to methotrexate. METHODS: Patients (n = 240) were randomized to receive ABT‐122 (120 or 240 mg every week), adalimumab (40 mg every other week), or placebo in a 12‐week double‐blind, parallel‐group study. The primary efficacy end point was the proportion of patients achieving ≥20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 12. Secondary and exploratory 12‐week end points included 50% improvement (ACR50) and 70% improvement (ACR70) response rates, and proportion of patients meeting the Psoriasis Area and Severity Index (PASI) response criteria for ≥75% (PASI75) and ≥90% (PASI90) improvement in skin scores among those with ≥3% of their body surface area affected by psoriasis. RESULTS: In both ABT‐122 dose groups, ACR20 response rates at week 12 (64.8–75.3%) were superior to that in patients receiving placebo (25.0%) (P < 0.001) but similar to that in patients receiving adalimumab (68.1%). ACR50 and ACR70 response rates were also superior in both ABT‐122 dose groups (36.6–53.4% and 22.5–31.5%, respectively) compared to the placebo group (12.5% and 4.2%, respectively) (P < 0.05). Among eligible patients in the placebo, adalimumab, ABT‐122 120 mg every week, and ABT‐122 240 mg every week treatment groups, PASI75 responses were achieved in 27.3%, 57.6%, 74.4%, and 77.6% of patients, respectively, whereas PASI90 responses were achieved in 18.2%, 45.5%, 48.8%, and 46.9% of patients, respectively. Frequencies of treatment‐emergent adverse events, including infections, were similar across all treatment groups, causing no discontinuations. No serious infections or systemic hypersensitivity reactions were reported with ABT‐122. CONCLUSION: Dual neutralization of TNF and IL‐17A with ABT‐122 had efficacy and safety that was similar to, and not broadly differentiated from, that of adalimumab over a 12‐week treatment course in patients with PsA.