[Adverse] Effect of Intra-articular Steroids

Michael Scally MD

Doctor of Medicine
10+ Year Member
[OA] McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017;317(19):1967–1975. Comparison of Intra-articular Triamcinolone vs Saline for Knee Osteoarthritis

Key Points

Question What are the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain in patients with osteoarthritis?

Findings In a randomized clinical trial of 140 patients with symptomatic knee osteoarthritis, the use of intra-articular triamcinolone compared with intra-articular saline resulted in greater cartilage volume loss. There was no significant difference on knee pain severity between treatment groups.

Meaning Among patients with symptomatic knee osteoarthritis, intra-articular triamcinolone, compared with intra-articular saline, increased cartilage volume loss and had no effect on knee pain over 2 years.


Abstract

Importance Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone.

Objective To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain.

Design, Setting, and Participants Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015.

Interventions Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years.

Main Outcomes and Measures Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94).

Results Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of −0.21 mm vs −0.10 mm (between-group difference, −0.11 mm; 95% CI, −0.20 to −0.03 mm); and no significant difference in pain (−1.2 vs −1.9; between-group difference, −0.6; 95% CI, −1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, −0.2%; 95% CI, −0.5% to −0.007%).

Conclusions and Relevance Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.
 
Long-Term Intra-Articular Steroid Injections and Knee Cartilage

They also question whether the results for cartilage volume loss represent a clinically meaningful risk because it was not detected by other feature scales and was nonsignificant in the completers’ analysis.

However, the cartilage thickness and damage index measurements were explicitly developed and optimized for their discriminative properties and also showed differences among completers, albeit with reduced power.

Although the group treated with triamcinolone did not exhibit any increase in functional decline, it is of concern that studies have consistently linked rate of cartilage loss to future risk for arthroplasty.

One study found that for every 1% increase in the rate of tibial cartilage loss, there was a 20% increased risk of undergoing a knee replacement at 4 years.4 The absolute increase in cartilage loss that we observed was 2% per year.

McAlindon TE, LaValley MP. Long-term Intra-articular Steroid Injections and Knee Cartilage—Reply. JAMA. 2017;318(12):1185–1186. Long-term Intra-articular Steroid Injections and Knee Cartilage


Luijsterburg PAJ, Bos PK, Bierma-Zeinstra SMA. Long-term Intra-articular Steroid Injections and Knee Cartilage. JAMA. 2017;318(12):1184. https://jamanetwork.com/journals/jama/article-abstract/2654805

Maloney WJ, Jevsevar DS, Shea KG. Long-term Intra-articular Steroid Injections and Knee Cartilage. JAMA. 2017;318(12):1184–1185. https://jamanetwork.com/journals/jama/article-abstract/2654806
 

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