Lutikizumab shows limited efficacy in knee osteoarthritis, synovitis
Inhibition of interleukin (IL)-1 with lutikizumab falls short in the treatment of patients with knee osteoarthritis (OA), with the results of a phase II study showing that the drug yields limited reductions in pain without any improvement in synovitis.
Researchers randomized 350 patients with Kellgren‐Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging or ultrasound) to receive placebo or lutikizumab 25, 100 or 200 mg subcutaneously every 2 weeks for 50 weeks. Of these, 60 of 85 patients (70.6 percent) in the placebo group and 202 of 265 (76.2 percent) in the lutikizumab groups completed the study.
Primary endpoints were change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain index at week 16 and in magnetic resonance imaging (MRI) synovitis at week 26.
At week 16, WOMAC pain decreased significantly with lutikizumab 100 mg (p=0.050) but not with the 25- and 200-mg doses relative to placebo. WOMAC pain improved in all groups thereafter, although the change was not significantly different between lutikizumab and placebo.
Additionally, changes in MRI synovitis at week 26 and other key symptom‐ and most structure‐related endpoints at weeks 26 and 52 did not markedly differ across the treatment groups.
Injection site reactions, neutropaenia and discontinuations due to neutropenia occurred with greater frequency in the lutikizumab groups vs placebo group. Neutrophil counts and high‐sensitivity C‐reactive protein values decreased at all time points with lutikizumab 100 mg. Finally, immunogenic response exerted no meaningful effect on systemic lutikizumab concentrations.
The present data suggest that IL-1 inhibition is not an effective disease-modifying therapy in patients with knee OA, researchers said. More studies are needed to determine whether subgroups of knee OA patients might have symptomatic benefit from IL-1 inhibition.