Wang SX, et al. - This article was written with the objective to research the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis. It was concluded that the ABT-981 was generally well tolerated in patients with knee osteoarthritis and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven osteoarthritis.

Methods

• For this research, they conducted a randomized, double-blind, placebo-controlled, single-center study.
• This was the study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate osteoarthritis of the knee (NCT01668511).
• Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of 4 SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of 3 SC injections.
• The primary objectives of this study were the assessment of safety and tolerability.
• In this study, they evaluated a panel of serum and urine biomarkers of inflammation and joint degradation.

Results

• They randomized a total of 36 patients (ABT-981, n=28; placebo, n=8) in this study.
• Out of these 36 patients, 31 (86) finished the investigation.
• Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%).
• The most common AE reported with ABT-981 versus placebo was injection site erythema (14% vs 0%).
• ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen.
• Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein exhibited reducing trends with ABT-981.
• Antidrug antibodies were found in 37% of patients but were not related to the incidence or severity of AEs.