Evaluation of the benefit of corticosteroid injection prior to exercise therapy in patients with knee osteoarthritis: A randomized trial

Abstract

Purpose: Combined non-pharmacological and pharmacological treatment is recommended as optimal management of knee osteoarthritis (OA). However, the two treatment approaches have mostly been investigated separately. We aimed to assess the efficacy of combined intra-articular corticosteroid injection and exercise compared to placebo injection and exercise in patients with knee OA. Methods: This randomized, double blind, placebo-controlled trial running over 26 weeks was designed as a superiority study comparing the efficacy of a single intra-articular corticosteroid injection (1 mL of 40 mg/mL methylprednisolone dissolved in 4 mL 10 mg/mL Lidocaine) plus exercise, with a single placebo injection (1 mL isotonic saline mixed with 4 mL 10 mg/mL Lidocaine) plus exercise. Participants with clinical and radiographic knee OA were randomly allocated (1:1) to either corticosteroid (Steroid Group) or saline (Placebo Group) injection. Two weeks after injection, all participants started a 12 week supervised exercise program with 3 weekly sessions. Outcomes were assessed at baseline, week 2 (exercise start), week 14 (end of exercise), and week 26 (follow-up). The primary outcome was the mean change in KOOS pain subscale at week 14. Analyses were done on the intention-to-treat (ITT) population (all randomized participants). Missing data were replaced using multiple imputation. A repeated measures mixed model was used to analyze the primary outcome; week, treatment, and week x treatment were included as fixed effects, adjusting for the baseline value. Results: A total of 263 patients were screened and 100 patients were randomized to receive either Steroid (n=50) or Placebo (n=50). Of these, 93 completed the week 14 assessment and 89 completed the 26 weeks trial. There were no group differences in the proportions completing. Mean age was 63.4 (SD 9.3) years, 61% were women. The mean exercise attendance rate was 79% (SD 15); no group difference observed. The mean (SD) KOOS pain score at randomization was 53.3 (11.4) and 55.2 (16.0) in the Steroid and Placebo groups, respectively. The mean (SE) change in pain at week 14 was 13.6 (1.8) and 14.8 (1.8) in the Steroid and Placebo Groups, respectively, corresponding to a mean difference of 1.2 units (95% CI -3.8 to 6.2; P=0.64). These results were robust according to all sensitivity analyses - incl. using baseline observation carried-forward imputation and no imputation. There were no group differences at week 2, 14, and 26 in any of the 5 KOOS subscales and the 95% confidence intervals of the group differences did not exceed the suggested minimal clinical important difference of 8-10 KOOS points. Conclusions: These results show comparable efficacy of intra-articular corticosteroid and placebo when combined with exercise for pain relief in knee OA. Trial registration. EU clinical trials register (EudraCT): 2012-002607-18 and clinicaltrials.gov NCT01945749