The use of ABT-122 in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) receiving background methotrexate demonstrated acceptable tolerability and maintenance of efficacy for up to 36 weeks, according to the results of two 24-week, open-label extensions (ClinicalTrials.gov identifiers: NCT02433340, NCT02429895) of phase 2, randomized, double-blind studies. The results were published in Rheumatology.
The investigators sought to assess maintenance of efficacy and safety of ABT-122, a bispecific monoclonal antibody that targets tumor necrosis factor and interleukin-17A, in patients with RA or PsA. The participants received ABT-122 administered subcutaneously every other week along with methotrexate. A total of 158 patients with RA were treated with 120 mg of ABT-122 and 168 patients with PsA were treated with 240 mg of ABT-122. Efficacy was evaluated using American College of Rheumatology (ACR) responses, 28-joint Disease Activity Score (DAS28) using high-sensitivity C-reactive protein (hsCRP), and Psoriasis Area and Severity Index (PASI). Safety assessments included laboratory parameters and occurrence of adverse events.
In the RA study, the incidence of treatment-emergent adverse events was 41%, which was similar to that of the double-blind study (36% to 43%). In the PsA study, 57% of participants reported ≥1 treatment-emergent adverse event, compared with 42% to 53% of those in the double-blind study. Most of the treatment-emergent adverse events were mild to moderate in severity. No neutrophil abnormalities >grade 2 were reported. Grade 3 or 4 laboratory abnormalities were reported for lymphocytes, hemoglobin, alanine aminotransferase, aspartate aminotransferase, and bilirubin. The number of these severe laboratory values was considered to be low (between 0.6% and 3.0%), except for grade 3 lymphocyte count, which decreased in the RA study (11.5%).
In both the RA study and the PsA study, efficacy evaluated by ACR responses and other disease activity scores, including DAS28 (hsCRP) and PASI, was maintained over 24 weeks.
The investigators concluded that despite the overall safety of ABT-122 reported in these 2 open-label extensions, because of the lack of clinically important differentiation from TNF inhibition alone, as provided by adalimumab, additional development of ABT-122 for the treatment of patients with RA and PsA is not being pursued.
Genovese MC, Weinblatt ME, Mease PJ, et al. Dual inhibition of tumour necrosis factor and interleukin-17A with ABT-122: open-label long-term extension studies in rheumatoid arthritis or psoriatic arthritis [published online July 18, 2018]. Rheumatology (Oxford). doi:10.1093/rheumatology/key173