Intra-articular corticosteroid injections for symptomatic osteoarthritis: The effects of injection dose, frequency, and timing on safety - PROJECT SUMMARY / ABSTRACT Osteoarthritis (OA) is the most common type of arthritis and a frequent cause of pain and disability. Osteoarthritis annually affects ~595 million adults globally, with anticipated rises in incidence due to aging of the population. Treatment guidelines for symptomatic OA of the knee, hip, and shoulder recommend non- surgical intervention as first-line care to delay or avoid joint replacement surgery. Intra-articular corticosteroid (IACS) injections are routine outpatient procedures for OA to reduce pain, decrease reliance on oral analgesic medications, and improve function and quality of life. Patients often report weeks to months of benefit and often receive several injections per year. Yet, uncertainty remains about the safety of single and repeated IACS injections. Systemic corticosteroids (often delivered orally or intravenously) are associated with serious adverse effects, including impaired immune response, cardiovascular disease, and accelerated osteoporosis. These risks are tolerated for corticosteroid treatment of life-threatening conditions, but risk tolerances are typically lower for elective procedures such as IACS injection. However, even though IACS injections result in systemic corticosteroid absorption, there is a lack of rigorous evidence about their safety. Most evidence comes from randomized trials that exclude high-risk patients and are limited by small sample sizes and short follow-up. Small clinical studies of the effects of IACS injections have demonstrated elevations in blood pressure and blood glucose, reductions in bone density, and increased risk of infection, but larger studies are needed. There is no evidence-based consensus on the maximum safe exposure level with respect to modifiable IACS injection factors including dose, timing, or frequency. Consequently, treatment guidelines for OA are inadequate and fail to offer best practice recommendations regarding maximum safe doses, maximum number of injections per year, minimum time interval between injections, or considerations for high-risk patients. Overall, the lack of evidence may lead to potential unnecessary harm. Rigorous evidence is needed to guide optimal pain management strategies to treat OA and determine the maximum safe exposure level of IACS injections. To fill this knowledge gap, we propose a large, non-experimental study to examine the utilization and safety of IACS injections. We will use Medicare claims data with ~17.4 million older adult recipients of IACS injections for the treatment of symptomatic OA of the knee, hip, or shoulder. We will characterize patterns of use of IACS injections and examine whether more frequent, closely spaced, and higher dose exposure to IACS injections are associated with increased risk of an array of individual adverse events (e.g., infections, cardiovascular events, osteoporotic fractures). We will perform subgroup analyses in medically complex patients. This large study will generate evidence to address critical gaps in knowledge about how to optimize the safety of IACS injections to treat symptomatic OA. Results will inform shared clinical decision-making, prevent harms, and promote continued independence among older adults in the community.
