Macrophage-reprogramming agent shows durable efficacy at 6 months in osteoarthritis

A novel agent designed to shift macrophages towards an anti-inflammatory phenotype maintained its therapeutic effect through 6 months. The benefit appeared most pronounced in older patients with osteoarthritis (OA), suggesting a potential link with immune ageing.

As Prof. Philip G. Conaghan (University of Leeds, United Kingdom) explained, allocetra is an off-the-shelf, cost-effective, apoptotic cell therapy administered via intra-articular injection [1]. The therapeutic rationale is based on reprogramming macrophages towards a more anti-inflammatory phenotype. In a phase 1/2a randomised study, 134 patients with symptomatic moderate-to-severe knee OA received 3 intra-articular injections of allocetra at weeks 0, 14, and 28. The injections were generally well tolerated. Local adverse events, including knee pain or discomfort, occurred in 73% of patients receiving allocetra and 79% of those receiving placebo, while knee swelling and reduced range of motion occurred in 79% and 33% of patients receiving placebo, respectively. These events were mostly mild to moderate and transient.

At 6 months, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved numerically with allocetra compared with placebo in the modified intention-to-treat (mITT) population (−21.8 vs −20.8; P=0.79). A statistically significant benefit was observed in patients aged ≥64 years (−26.6 vs −11.1; P=0.01). This age-related treatment effect was observed across other efficacy measures, including WOMAC pain and Outcome Measures in Rheumatology (OMERACT).

The investigators suggested that the treatment target may be linked to immunosenescence and immune ageing, indicating that the observed efficacy is associated with age-related changes in the immune system.

“This is a target that is likely related to immunosenescence. This is hopefully opening a new door to treatment pathways,” Prof. Conaghan concluded. A phase 2b trial is currently underway.

Conaghan Ph. Durable Efficacy at 6 Months Using an Innovative Intra-Articular Apoptotic Cell Therapy in Knee Osteoarthritis: Data from a Phase IIA RCT. OP060, EULAR 2026, 3–6 June, London, United Kingdom.