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.

Trial registration: ClinicalTrials.gov NCT02349451.

Figure 1

Disposition of the study patients. EW = every week; EOW = every other week.

Figure 2

End point analyses in patients with psoriatic arthritis in the different treatment groups. A–C, Proportion of patients achieving ≥20% improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) (A), as well as 50% (ACR50) (B) and 70% (ACR70) (C) improvement response rates, over the 12‐week treatment course (with nonresponder imputation). D, Least squares mean change in the Disease Activity Score in 28 joints using high‐sensitivity C‐reactive protein level (DAS28‐hsCRP) (with last observation carried forward imputation). E, Mean change in scores on the Stanford Health Assessment Questionnaire modified for the spondyloarthritides (HAQ‐S) (with last observation carried forward imputation). No statistical testing was done for the mean change in HAQ‐S scores; it was only done for the responder definition of a score increase of ≥0.5. * = P < 0.05; ** = P < 0.01; *** = P < 0.001 for ABT‐122 versus placebo. † = P < 0.05; &ddagger; = P < 0.01; § = P ≤ 0.005 for ABT‐122 versus adalimumab. EOW = every other week; EW = every week.

Figure 3

Proportion of patients meeting the Psoriasis Area and Severity Index (PASI) response criteria for ≥75% (PASI75) and ≥90% (PASI90) improvement in skin scores (with nonresponder imputation) at 12 weeks among those with ≥3% of body surface area affected by psoriasis at baseline. * = P < 0.01 for ABT‐122 versus placebo; † = P < 0.05 for ABT‐122 versus adalimumab. EW = every week; EOW = every other week.

Figure 4

Treatment responses in the joints and skin at 12 weeks in the ABT‐122 120 mg every week or 240 mg every week groups as compared to the adalimumab group. A, Joint responses at 12 weeks were measured according to the American College of Rheumatology response criteria of ≥20% (ACR20), ≥50% (ACR50), and ≥70% (ACR70) improvement, score thresholds of <3.2 and <2.6, as well as change from baseline (CFB) ≤−1.2, for the Disease Activity Score in 28 joints using high‐sensitivity C‐reactive protein level (DAS28‐hsCRP), and CFB ≤−0.5 in the score on the Stanford Health Assessment Questionnaire modified for the spondyloarthritides (HAQ‐S). B, Skin responses at 12 weeks in patients with ≥3% body surface area affected by psoriasis at baseline were measured as a score of 0 or 1 on the physician's global assessment of psoriatic disease activity (PhGAPsO) (full scale 0–6) and as the proportion of patients achieving improvement in skin scores according to the Psoriasis Area and Severity Index response criteria of ≥50% (PASI50), ≥75% (PASI75), and ≥90% (PASI90) improvement. All analyses used last observation carried forward imputation. Bars show the difference in response with 95% confidence interval (95% CI). EW = every week.