Reduction of Systemic Exposure and Side Effects by Intra-articular Injection of Anti-inflammatory Agent for Osteoarthritis: What is the Safer Strategy?

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease associated with pain, inflammation, and cartilage degradation. However, no current treatment can effectively halt the progression of the disease. Therefore, the use of NSAIDs and intra-articular corticosteroids is usually recommended as the primary treatment for OA-associated pain and inflammation. However, there is accumulating evidence that the long-term use of oral NSAIDs and intra-articular corticosteroids can lead to a myriad of negative side effects. Although numerous efforts have been made to develop intra-articular formulations for NSAIDs, the systemic exposure of intra-articular injection of NSAIDs and its potential side effects have not been explicitly investigated. To ascertain the evident and potential side effects of intra-articular injection of anti-inflammatory agents, we have summarized in this review the systemic exposure, local side effects, and systemic side effects of intra-articular injections of anti-inflammatory agents, including NSAIDs and corticosteroids. For developing a safer treatment to fulfill the unmet long-term use needs of patients, a new therapy, which combines locally active drugs and sustained-release formulations, has been proposed in this review.