Recombinant equine lubricin is safe and well tolerated following multiple intra-articular injections in healthy fetlock joints

Objective To assess the safety of recombinant equine lubricin (rEqLub) injections in healthy equine fetlocks using clinical, biochemical, and histological outcomes. Methods 6 adult horses were enrolled (3geldings, 3mares) in a block randomized, controlled experimental study. All 24 fetlocks were assigned to receive an injection of either 2 mL rEqLub (1mg/mL) or PBS at 1 of 3 time points. Recombinant equine lubricin was injected into a randomized forelimb at 28 days and 1 day prior to study completion, and rEqLub and PBS were injected into contralateral hindlimbs at 7 days prior to study completion. Clinical and orthopedic examinations were performed at baseline and prior to and 1 day following each injection; synovial fluid was collected for biochemistry, flow cytometry, and proteomics; synovial membrane and osteochondral sections were collected from day-28 rEqLub-treated joints and scored using Osteoarthritis Research Society International criteria. Results 3 sequential IA injections of rEqLub in 3 different healthy fetlocks were well tolerated and did not result in adverse clinical or histologic outcomes. There were no differences in clinical or synovial fluid biochemical parameters between rEqLub- and PBS-injected joints. Synovial fluid WBC concentrations and total protein were increased 1 day after injection in rEqLub-treated joints. Conclusions IA rEqLub did not cause any detectable clinical, biochemical, or histological adverse effects, supporting the favorable tolerability and safety profile of rEqLub. The small sample size and multijoint design are limitations. Clinical Relevance rEqLub injections were well tolerated, establishing a basis for future equine efficacy trials to evaluate the ability of recombinant lubricin to mitigate osteoarthritis in a clinically relevant equine model.