ABT-122, a Bispecific Dual Variable Domain Immunoglobulin Targeting Tumor Necrosis Factor and Interleukin-17A, in Patients With Rheumatoid Arthritis With an Inadequate Response to Methotrexate: A Randomized, Double-Blind Study

Abstract

Objective: Tumor necrosis factor (TNF) and interleukin-17A (IL-17A) may independently contribute to the pathophysiology of rheumatoid arthritis (RA). This study sought to evaluate the safety and efficacy of ABT-122, a novel dual variable domain immunoglobulin targeting human TNF and IL-17A, in patients with RA who have experienced an inadequate response to methotrexate.

Methods: Patients with active RA who were receiving treatment with methotrexate and had no prior exposure to biologic agents (n = 222) were enrolled in a 12-week phase II randomized, double-blind, active-controlled, parallel-group study. Patients were randomized to receive either ABT-122 at dosages of 60 mg every other week, 120 mg every other week, or 120 mg every week or adalimumab at 40 mg every other week, administered subcutaneously. The primary efficacy end point was the proportion of patients achieving a ≥20% improvement response based on the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12.

Results: Treatment-emergent adverse events were similar across all treatment groups, with no serious infections or systemic hypersensitivity reactions reported with ABT-122. ACR20 response rates at week 12 were 62%, 75%, and 80% with ABT-122 60 mg every other week, 120 mg every other week, and 120 mg every week, respectively, compared with an ACR20 response rate of 68% with 40 mg adalimumab every other week. The corresponding response rates for ACR50 and ACR70 improvement in the ABT-122 dose groups and adalimumab group were 35%, 46%, 47%, and 48%, respectively, and 22%, 18%, 36%, and 21%, respectively.

Conclusion: Over the 12-week study period, dual inhibition of TNF and IL-17A with ABT-122 produced a safety profile consistent with that of adalimumb used for inhibition of TNF alone. The efficacy of ABT-122 over 12 weeks at dosages of 120 mg every other week or 120 mg every week was not meaningfully differentiated from that of adalimumab at a dosage of 40 mg every other week in patients with RA receiving concomitant methotrexate.

Trial registration: ClinicalTrials.gov NCT02141997.

© 2018, American College of Rheumatology.

Figures

Figure 1

Disposition of the study patients. SC = subcutaneous; EOW = every other week; EW = every week; AE = adverse event.

Figure 2

Percentage of patients in each treatment group achieving improvement according to the American College of Rheumatology response criteria for an improvement of at least 20% (ACR20) (A), 50% (ACR50) (B), and 70% (ACR70) (C) over the 12‐week treatment course (full analysis set, nonresponder imputation). SC = subcutaneous; EOW = every other week; EW = every week.

Figure 3

Differences in efficacy end points at 12 weeks between the ABT‐122 dosing groups compared with the adalimumab group. The end points include the American College of Rheumatology response criteria for an improvement of at least 20% (ACR20), 50% (ACR50), and 70% (ACR20), 2 score cutoffs for the Disease Activity Score in 28 joints based on high‐sensitivity C‐reactive protein level (DAS28‐hsCRP), 2 score cutoffs for the Clinical Disease Activity Index (CDAI), and change from baseline (CFB) of ≤−1.2 in the DAS28‐hsCRP score or ≤−0.5 on the disability index (DI) of the Health Assessment Questionnaire (HAQ). Bars show the difference in response with 95% confidence interval (95% CI). EOW = every other week; EW = every week.