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.

Abstract

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.

• Authors: Philip J Mease, Mark C Genovese, Michael E Weinblatt, Paul M Peloso, Kun Chen, Ahmed A Othman, Yihan Li, Heikki T Mansikka, Amit Khatri, Neil Wishart, John Liu
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 70 Issue 11 Pg. 1778-1789 (11 2018) ISSN: 2326-5205 [Electronic] United States
• PMID: 29855175 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 AbbVie Inc. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Chemical References

• ABT-122
• Antirheumatic Agents
• IL17A protein, human
• Immunoglobulins
• Interleukin-17
• TNF protein, human
• Tumor Necrosis Factor-alpha
• Methotrexate

Topics

• Adult
• Antirheumatic Agents (therapeutic use)
• Arthritis, Psoriatic (drug therapy)
• Double-Blind Method
• Female
• Humans
• Immunoglobulins (therapeutic use)
• Interleukin-17 (antagonists & inhibitors)
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)