Long-term effects of intra-articular corticosteroid injections among knee osteoarthritis patients: an instrumental variable and propensity score analysis

Background: Intra-articular corticosteroid injections (IACI) are recommended in the UK by NICE as an adjunctive treatment for uncontrolled pain from osteoarthritis (OA).


Objectives: We assessed the long-term effect of IACI use on pain medication prescriptions and subsequent joint replacement among people with incident knee OA.


Methods: Study design and setting: Cohort study in UK using primary-care (CPRD GOLD) and linked hospital data (Hospital Episode Statistics). Source population: Patients ≥20 years with a first diagnosis of knee OA during 2005-2019, excluding those with a prior orthopaedic surgery referral. Exposure: IACI. Outcomes: Primary outcomes were incident pain medication prescriptions and knee replacement. Among those who received knee replacement, secondary outcomes included: complications (stroke, myocardial infarction, thrombosis, or joint infection), re-operation and patient reported outcome measures. Statistical analysis: Instrumental variable (IV) analyses were used. Index date was six months after OA diagnosis date and IV was defined as GP practice preference for IACI use in the year prior to index date (single and recurrent use considered separately). Outcomes were measured over five years from index date. Covariate balance was assessed, and two-step Poisson regression used where IV assumptions met. Propensity score (PS) matching was carried out in secondary analyses using time-varying exposure Cox regression models.


Results: Of 114,528 eligible patients, up to 99,661 (87.0%) were retained in prescription analyses and up to 44,985 (39.3%) in joint replacement analyses. Patient characteristics were well balanced (SMD ≤0.1) across IV groups, except in analysis of repeat IACI on joint replacement. IACI was associated with lower 5-year cumulative incidence of most pain medications, e.g. for partial opioids a relative risk (RR) of 0.62 [95% CI 0.44, 0.87] and 0.39 [0.23, 0.65] for single and recurrent IACI, respectively. There were 2,728 knee replacements during five years follow-up, with single IACI associated with lower cumulative incidence: RR 0.52 [0.34, 0.80]. PS matching confirmed the association between IACI and reduced incidence of several pain medications, but suggested higher incidence of knee replacement over the long-term (5 years): hazard ratio (HR) 2.13 [1.90, 2.40] and HR 2.20 [1.88 to 2.58] for single and repeat IACI, respectively. IACI had no adverse impact on secondary outcomes after joint replacement.


Conclusions: Findings suggest IACI use for knee OA may reduce subsequent need for analgesics and delay knee replacement with no adverse effect on outcome. However, results for knee replacement were not consistent in secondary analyses, therefore further investigation is required.