Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain
Share |

Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain

Team Representative:
Timothy McAlindon, DM, MPH
Chief, Division of Rheumatology, Tufts Medical Center
E-mail: tmcalindon@tuftsmedicalcenter.org
Phone: 617-636-5645

Media Contact:
Rhonda Mann
E-mail: rmann1@tuftsmedicalcenter.org
Phone: 617-636-3265

Summary of findings in laymen's terms: 

Painful knee osteoarthritis (OA) affects 10% of the population over 55 years, and is a major cause of work loss, early retirement and joint replacement yet there are few effective treatments and none known to stop it from progressing. The study was done to find out if corticosteroid injections, administered every three months for 2 years into knees with OA and some evidence of inflammation, reduce knee OA cartilage damage, and benefit pain and functional ability in the long-term. However, another important reason to test corticosteroid injections was to see if they damage to joint structures, which has been a longstanding concern.

The study used state-of-the -art imaging and image analysis technologies to detect inflammation and measure damage in cartilage and the surrounding bone. There were 140 patients (mean age, 58[8], 75 (54%) women), of whom 70 were randomly assigned to steroid injections and 70 to an inert placebo injection. 119 (85%) completed the study. Participants had assessments of pain and function at each of the 3-monthly visits; and had MRI scans of their knee at baseline, 12 and 24 month visits. The group who received the steroid injections had more cartilage damage and there was no difference between the groups in measures of pain or physical function. There were few side-effects and these did not differ between groups.

The study showed that, for patients with painful knee osteoarthritis with inflammation, repeated steroid injections into the knee over 2 years of intra-articular does not benefit symptoms and is associated with more cartilage damage. Although the cartilage loss was not associated with worsening of symptom outcomes in the study itself, the finding is of concern because research has shown that faster cartilage loss in individuals is associated with higher rates of future knee joint replacement. 

Specific biological innovation of study: 

This study was predicated on a recent paradigm shift in views of the role of inflammation in osteoarthritic joints. A range of studies have revealed that some degree of inflammation is usual in the synovium of OA knees and suggest that its presence predicts progression of structural damage. This trial was thus predicated on the hypothesis that suppression of inflammation in OA knees would reduce progression of damage to cartilage and peri-articular bone.

In addition, measurement of changes in articular soft-tissue structures with precision and good discrimative validity has been a technological obstacle in this field. Consequently, there have been few clinical trials in the field of OA that were aimed at structure modification.

This study used MRI to image the knee joints, including sequences optimized for delineation of cartilage and bone marrow lesions. We deployed innovative computer-assisted measurement techniques that we developed in the course of our programmatic focus on structure modification in OA. This included quantitative measurements of cartilage thickness and a Cartilage Damage Index that we specifically developed and validated to have a high degree of discriminative validity. These two measures consistently demonstrated greater cartilage loss in the treated arm. We also performed quantitative measurements of bone marrow lesion and effusion volume. The study also used ultrasonographic assessment of effusion/synovitis and measurement of peri-articular bone density using dual x-ray absorptiometry. 

Potential impact on human care and/or how the findings contributed to an improved understanding:

This study was done to determine if IACS might reduce the rate of cartilage loss and structural manifestations of OA. Suppression of inflammation could attenuate catabolic effects of inflammation and reduce articular damage. The use of MRI in this study enabled direct quantitation of cartilage and soft-tissue structures. The 2-year change in the index compartment cartilage thickness was greater in the steroid group (between group difference of -0.11 mm, 95% confidence limits -0.20, -0.03), which corresponds to a moderate effect size of 0.46. The effects that were detected on cartilage loss were statistically significant and consistent across different measurements. The minimally clinically important difference (MCID) cartilage loss is not established, however, the observed change was smaller than the differences between one KL grade measured. Increased progression was not detected in other OA features, structural or clinical. The results are consistent with in-vivo and clinical research showing catabolic effects of corticosteroids. Rate of cartilage loss have been associated with higher rates of arthroplasty, raising the possibility of potential for adverse consequences on the health of the joint in the longer term.

In conclusion, among patients with symptomatic knee OA, 2 years of intra-articular steroids resulted in more cartilage volume loss and no difference in knee symptoms. These findings do not support this treatment for patients with symptomatic knee osteoarthritis. As a proof-of-concept study, the results question the role of inflammation in OA progression. 

Journal citation:

McAlindon, Timothy E., Michael P. LaValley, William F. Harvey, Lori Lyn Price, Jeffrey B.Driban, Ming Zhang, and Robert J. Ward. "Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial." JAMA 317, no. 19 (2017): 1967-1975.