IL-1 Inhibition Not Significantly Effective for Knee OA and Synovitis

A recent phase 2 trial evaluated the impact of the anti‐interleukin (IL)‐1α/β dual variable domain immunoglobulin lutikizumab (ABT‐981) in knee osteoarthritis (OA) patients with synovitis. The study found limited pain improvement and improved synovitis.

The study, published in Arthritis & Rheumatology, assessed 347 patients with Kellgren‐Lawrence grade 2–3 knee OA and synovitis as evidenced by MRI or ultrasound. Patients were randomized to receive placebo or 25 mg, 100 mg, or 200 mg of lutikizumab every other week for 50 weeks. Primary endpoints were 16-week changes in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain index and 26-week changes in MRI synovitis.

Compared to the placebo cohort, patients receiving 100 mg of lutikizumab had significantly improved WOMAC pain after 16 weeks (P = 0.050)—a difference not observed in the other lutikizuamb dosage groups. After the 16-week mark, all patients had decreased WOMAC pain, but outcomes did not greatly differ between the lutikizumab and placebo groups. Week 26 synovitis did not significantly differ between the lutikizumab and placebo groups; neither did many other symptom- and structure-related outcomes at the 26- and 52-week marks. Lutikizumab patients had higher rates of injection site reactions, neutropenia, and discontinuations due to neutropenia compared to the placebo patients.

“The limited improvement of WOMAC pain and the lack of synovitis improvement with lutikizumab, together with published trial results for other IL‐1 inhibitors, suggest that IL‐1 inhibition is not an effective analgesic/anti‐inflammatory therapy in most patients with knee OA and associated synovitis,” the researchers wrote.

The phase 1 trial found improved outcomes for knee OA patients, reporting “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.”

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Source: Arthritis & Rheumatology