Shelby Brigman, Mercer University College of Pharmacy
Osteoarthritis (OA) of the knee is characterized by the progressive destruction of articular cartilage, synovium, capsule, and subchondral bone. Surrounding ligaments and muscles can also be affected. Changes in these tissues lead to clinical development of symptoms such as joint pain and tenderness with decreased range of motion, weakness, and joint instability.1
The American College of Rheumatology guidelines for osteoarthritis of the knee recommend intra-articular corticosteroid injections when a satisfactory clinical response is not seen with full-dose acetaminophen (Tylenol ®).2 Similarly, the National Institute for Health and Care Excellence (NICE) guidelines recommend intra-articular corticosteroid injections be considered only as an adjunct to core treatments (non-surgical: exercise and weight loss) for the relief of moderate to severe pain.3
|Title: Evaluation of the Benefit of Corticosteroid Injection Before Exercise Therapy in Patients with Osteoarthritis of the Knee4|
|Design||Randomized, blinded, placebo-controlled trial; N = 95|
|Objective||To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee|
|Study Groups||Participants received either intra-articular injection of the knee with methylprednisolone acetate (Depo-Medrol®) or isotonic saline injection (placebo)|
|Methods||All participants were diagnosed with tibiofemoral OA with clinical signs of localized knee inflammation, knee pain during walking (score greater than four), and a body mass index of 35 or less. Participants chose the most symptomatic knee as the target knee for treatment. Participants were randomized 1:1 to either treatment or placebo group and received either intra-articular 1 mL injection of the knee with methylprednisolone acetate 40 mg/mL dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) or a 1 mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL). Two weeks after the injections, all participants started a 12-week supervised exercise program. Outcomes were measured at baseline, at the start of the exercise program (week two), after the exercise program (week 14), and after 12 weeks of follow-up (week 26).|
|Duration||October 2012 – April 2014|
|Primary Outcome Measure||Change in the pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire at week 14|
|Baseline Characteristics||Mean age = 63.4, 61% female, KOOS pain subscale score at baseline = 54.3|
|Results||The change in the pain subscale KOOS at primary endpoint week 14 from baseline in the placebo group was 14.8 and was 13.6 in the corticosteroid group. The mean difference in the change from baseline between groups in Pain subscale score was 1.2 KOOS points (95% CI, −3.8 to 6.2 [P = .64]).|
|Adverse Events||None reported|
|Study Author Conclusions||Our results suggest no additional clinical benefit by adding 40 mg of methylprednisolone acetate to an intra-articular injection of saline and lidocaine before exercise in patients with OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments of OA of the knee.|
The study results revealed no additional benefit of adding methylprednisolone acetate as an intra-articular injection in patients with OA of the knee. However, in order to have 91% statistical power to detect a reduction in the KOOS pain subscale that was ten points larger than placebo, the study required a population of 100 patients in the intent-to-treat (ITT) population. The study population in the ITT analysis included only 95 patients and therefore was not adequately statistically powered. It is possible that with an adequate study population, different results may have been seen. It was also noted that the dose of corticosteroid used was in the lower range of doses recommended for OA of the knee joint, and it is possible that beneficial effects were not seen because of the sub-therapeutic dose. The fact that the dose-response relationship of using this injection is unknown was noted, so it is difficult to determine if the dosing used was a true limitation to the results. In future studies, an adequate statistical power and pre-determined therapeutic dose may show beneficial results.
1.) Buys LM, Elliott M.Chapter 71. Osteoarthritis. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310523. Accessed June 15, 2015.
2.) Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74.
3.) National Clinical Guideline Centre. Osteoarthritis. Care and management in adults. London (UK): National Institute for Health and Care Excellence (NICE); 2014 Feb. 36 p.
4.) Henriksen M, Christensen R, Klokker L, et al. Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial. JAMA Intern Med. 2015;175(6):923-30. doi: 10.1001/jamainternmed.2015.0461.