In equine practice, a common strategy for management of osteoarthritis is the use of intra-articular (IA) injections of corticosteroids and/or administration of oral nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroids are not without adverse effects, particularly with frequent use—erosion of cartilage, or systemic side effects in horses with metabolic issues. NSAIDs also create potential adverse effects of stomach or colonic ulcers and gastrointestinal dysbiosis.
Doctors at Walter Reed Army Institute of Research and Medical Center and at the Georgetown University School of Medicine did a retrospective study of 1032 results from the National Library of Medicine Database about use of intra-articular injection of NSAIDs in humans and animals. [Selig DJ, Kress AT, Horton IM, et al. Pharmacokinetics, safety and efficacy of non-steroidal anti-inflammatory drug injections for the treatment of osteoarthritis: A narrative review. Journal of Clinal Pharmacology and Therapeutics Mar 2022; DOI: 10.1111/jcpt.13669]
To date, there is no FDA-approved NSAID injection for intra-articular use although a plethora of oral, intravenous, and topical forms exist. This study reviewed IA use of traditional NSAIDs and their pharmacokinetics, efficacy and safety profiles when used in animals and humans. The medications examined included indoprofen, ketorolac, parecoxib, and tenoxicam.
In safety studies, IA NSAIDS administered to healthy joints sometimes elicit non-specific inflammation, possibly due to high volumes of injected medication. However, when used in arthritic joints, IA NSAIDs achieved control of inflammation and pain while also reducing nociception and clinical swelling and improving weight bearing. These results were comparable to NSAIDs given orally or intramuscularly.
It was further identified that similar to IV or IM dosing, IA NSAIDs also result in systemic exposure due to diffusion of the medication from the joint space into the plasma. However, oral dosing does potentially result in up to seven times more systemic exposure than an IA injection. Yet within the joint, a single IA dose leads to a 2-3 log-fold increase in the synovial fluid when compared to dosing given orally or topically. Repeat oral doses tend to result in higher sustained synovial NSAID concentrations compared to a single IA dose. Pain control and stiffness were ameliorated similarly in both the oral and IA groups.
A formulation of IA diclofenac is conjugated to hyaluronic acid (DF-HA) and may prolong residence time within the joint while minimizing systemic exposure. Studies indicate that there is no need to repeat DF-HA injections within 24 weeks of a single administration. More research needs to follow from initial trails.
The authors suggest: “Alternating IA NSAIDs with IA corticosteroids may be a sound approach to spare the long-term degenerative effects of corticosteroids on cartilage and bone. There are also several other possible indications for IA NSAIDs such as acute sports injuries or as an adjunct to improve analgesia for arthroscopy.”
Animal efficacy studies indicate that “IA NSAIDs are efficacious and as effective as oral NSAIDs within those controlled experiments.” In summary, a single IA NSAID injection results in higher synovial maximum NSAID concentrations with considerably less systemic and synovial exposure compared to a one-week course of oral NSAIDs.