RecUrrent Intra-articular Corticosteroid injections in Osteoarthritis: the RUbICOn mixed-methods study.

Background: Intra-articular corticosteroid injections are an adjunct to core treatments for osteoarthritis. The National Institute for Health and Care Research Health Technology Assessment programme commissioned this research to address uncertainty around the long-term benefits and potential risks associated with recurrent intra-articular corticosteroid injections. Objectives: Characterise current intra-articular corticosteroid injection practice. Establish longer-term effects and safety of single and recurrent intra-articular corticosteroid injections. Explore views and experiences of patients and clinicians. Assess the priorities/feasibility for future research. Methods: A cohort study of incident osteoarthritis patients (2005-20) was performed using United Kingdom primary care data (Clinical Practice Research Datalink) linked to hospital data (Hospital Episode Statistics). Incidence of first intra-articular corticosteroid injection was stratified by age, calendar year, gender and geographical region. Longer-term outcomes included incident pain medication and joint replacement. Instrumental variables based on practice preference for intra-articular corticosteroid injection were used in primary analyses. Safety was assessed with propensity score matching and a self-controlled cohort, with outcomes (mortality, bleeding, hemarthrosis, wound infection, diabetes, stroke, ischaemic heart disease, myocardial infarction) assessed at 6 months. Semistructured telephone/videocall interviews were conducted (patients = 38, primary care clinicians = 19), with inductive thematic analysis used to investigate views and experiences of intra-articular corticosteroid injections. A three-round modified Delphi study with patients ( Results: There were 23,899 (10.8%) osteoarthritis patients receiving intra-articular corticosteroid injections (40% received > 1 injection). Incidence of intra-articular corticosteroid injection at 5-year follow-up was lowest for elbow (5.2%) and highest for shoulder (13.6%). Incidences remained stable for all joints between 2005 and 2019 but varied between regions {3.8 [95% confidence interval 3.4 to 4.1] to 1.4 [95% confidence interval 1.3 to 1.5] injections per 100 patient-years}. Intra-articular corticosteroid injection for knee osteoarthritis was associated with lower incident use of several pain medications at 5-year follow-up; recurrent knee intra-articular corticosteroid injections were associated with greater risk reduction. In primary analyses intra-articular corticosteroid injection was associated with a lower 5-year cumulative incidence of knee replacement (number needed to treat 17, 95% confidence interval 12 to 40), but not hip replacement. In certain analyses, incidences of diabetes, ischaemic heart disease and myocardial infarction were numerically higher with intra-articular corticosteroid injections but 95% confidence interval spanned the null; there were no significant associations with other outcomes. Qualitative interviews demonstrated clinicians were more cautious about administering intra-articular corticosteroid injections compared to patients considering receiving intra-articular corticosteroid injections. Patients valued intra-articular corticosteroid injections; however, access was variable, with contributory factors including clinician concerns about the evidence base and their individual competence and confidence performing intra-articular corticosteroid injections. The Delphi research priority list included 14 questions covering long-term effects, clinical and cost-effectiveness, outcomes measurement, comparison to other treatments, provision, safety, identifying responders, maximising benefits, patient experience, delaying joint replacement and dosage. Limitations: Observational analyses: Possibility of residual confounding. Qualitative research: Self-selecting nature of participation; and while the funding remit focussed on primary care, qualitative findings suggest orthopaedic consultants are key stakeholders. Delphi study: Unable to engage commissioners. Conclusions: Overall, in the UK, intra-articular corticosteroid injection use is unchanged over 15 years; however, there was wide regional heterogeneity. We observed a sustained reduction in usage of certain pain medications after intra-articular corticosteroid injections. Intra-articular corticosteroid injections appear generally safe, although more research is needed on potential safety signals, particularly diabetes and cardiovascular events. Future work: A Delphi study with key stakeholders identified 14 priority questions to guide future intra-articular corticosteroid injection research. Work exploring regional variation in intra-articular corticosteroid injection access would be beneficial. Study registration: This study is registered as ISRCTN32433800; Independent Scientific Advisory Committee (ISAC) for the Medicines and Healthcare Products Regulatory Agency (ISAC protocol no. 20_067RA). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129011) and is published in full in