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Monoclonal antibody shown to be safe, effective in managing PsA
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SAN DIEGO – Treatment with ABBV-066, a monoclonal antibody that inhibits interleukin-23, provided substantial improvements in joint and skin scores among patients with psoriatic arthritis, according to findings presented at the American College of Rheumatology Annual Meeting.
In addition, no novel or surprising side effects were observed with ABBV-066 (risankizumab, AbbVie) in this double-blind, dose-ranging Phase 2 study that used a parallel-group design.
“ABBV-066 is a potent, humanized immunoglobulin G1 monoclonal antibody that inhibits IL-23 by binding to its p19 subunit,” Philip J. Mease, MD, of the Swedish Medical Center and University of Washington School of Medicine, said during a presentation. “This agent has been shown to be highly effective in psoriasis. The purpose of this study was to provide proof-of-concept and evaluate the safety and efficacy of ABBV-066 in patients with active PsA.”
Mease and colleagues enrolled 185 patients in the trial. Participants were required to meet the ClASsification criteria for Psoriatic Arthritis, or CASPAR, and were grouped by prior exposure to tumor necrosis factor inhibitors or concurrent methotrexate use.
Patients were randomly assigned, in a 2:2:2:1:2 ratio, to receive ABBV-066 150 mg at Weeks 0, 4, 8, 12 and 16 (arm 1), 150 mg at Weeks 0, 4 and 16 (arm 2), 150 mg at Weeks 0 and 12 (arm 3), a single 75-mg dose at Week 0 (arm 4) or matching placebo (arm 5). Patients were grouped according to previous exposure to tumor necrosis factor inhibitors and concurrent methotrexate use.
The primary endpoint was ACR20 response at Week 16. Other efficacy endpoints included ACR50 and ACR70, minimal disease activity, DAS28 (C-reactive protein), the SpA Research Consortium of Canada Enthesitis Index, visual analog pain scale, Health Assessment Questionnaire Disability Index and dactylitis count. Psoriasis Area Severity Index scores were only evaluated in patients who had psoriasis affecting equal to or greater than 3% of their body surface area at baseline.
The median age of patients was 51 years and 43.2% (n = 80) were women. About half of the participants (49.4%; n = 89) were affected by psoriasis on 3% or more of their body surface area at baseline. Dactylitis or enthesitis was present in 30.4% (n = 56) and 64.7% (n = 119) of patients, respectively, at baseline.
Previous treatment with TNF inhibitors was reported in 24.3% of patients (n = 45) and more than half (57.3%; n = 106) were receiving concomitant methotrexate. Most patients (n = 172; 93%) treated with ABBV-066 finished a 16-week course of therapy.
“The arms were well-balanced in terms of baseline characteristics,” Mease said. “Patients were slightly heavier, as is consistent with the PsA population, and had about 6 to 8 years of disease duration.”
At Week 16, ACR20 responses improved more in patients treated with ABBV-066 across all dose arms (57.1%-65%) compared with patients receiving placebo (37.5%). ACR50 and 70 responses, as well as PASI75, 90 and 100 responses, were all higher at Week 16 among patients receiving ABBV-066. Improvements related to Health Assessment Questionnaire Disability Index and enthesitis scores from baseline increased among patients treated with ABBV-066, as did MDA, DAS28(CRP) and visual analog pain scale scores.
“MDA is a new threshold that we are looking at as a target for treatment,” Mease said. “MDA was achieved in all of the dose arms; between 30% and 35% of patients statistically separated from placebo.”
Treatment-related adverse events were similar across arms, with infection occurring the most frequently. No deaths or cases of tuberculosis occurred in patients receiving ABBV-066, although one adjudicated major adverse cardiovascular event was reported.
Mease highlighted ‘items of special interest’ during his presentation, including overall infection rate, serious infection rate, serious hypersensitivity, adjudicated major adverse cardiovascular events, malignancy and depression.
“Serious infection and malignancy occurred in a patient from our center, who was noted to have an ovarian carcinoma in advanced stage at month 6,” he said. “Serious hypersensitivity occurred in a patient who had not received previous biologic therapy. On her first injection, she experienced quite a bit of anxiety and elevated blood pressure; a drop in blood pressure was seen at the emergency room. She did not have a rash or other features relating to IgE-mediated anaphylaxis.”
ABBV-066 is moving forward in phase 3 clinical trials, according to Mease.
“In this study, ABBV-066 significantly improved joint and skin symptoms compared with placebo in patients with active PsA. The safety and tolerability profile was consistent with observations in previous ABBV-066 trials,” he said. “The dosing regimen and the radiographic data are pending as we await Week 24 data. That will allow us to judge what doses are best to carry forward.” – by Julia Ernst, MS
Reference:
Mease PJ, et al. Abstract 2L. Presented at: ACR Annual Meeting; Nov. 3-8, 2017; San Diego.
Disclosures: Mease reports financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma and UCB. Please see the full study for a list of all other researchers’ relevant financial disclosures.