Findings published in JAMA identified no significant difference in knee pain — but significant cartilage volume loss — in patients with knee osteoarthritis (OA) who underwent intra-articular triamcinolone injections vs saline placebo.1
Timothy E McAlindon, DM, MPH, of the division of rheumatology at Tufts Medical Center in Boston, Massachusetts, and colleagues conducted a randomized placebo-controlled double-blind trial to examine the effects of intra-articular triamcinolone acetonide 40 mg injection on progressive cartilage loss in knee OA.
The study (Effect of Steroid Injections in a Knee With Osteoarthritis [IACS for KOA]; ClinicalTrials.gov Identifier: NCT01230424) included 140 patients (mean age 58±8; 54% women) who met American College of Rheumatology (ACR) criteria for knee OA between 2013 and 2015 at Tufts Medical Center. Primary study outcomes were cartilage loss, articular structural damage, pain, and physical function, assessed via annual knee MRI and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) indices, collected every 3 months. Of the enrolled patients, 85% completed the study.
At each of the 9 post-screening visits, all patients were assessed via knee examination, blood pressure measurement, WOMAC questionnaire, and standardized semiflexed posteroanteroir knee radiographs, and knee and hip dual x-ray absorptiometry scans. Knee ultrasound and MRI scans were conducted at 0, 12, and 24 months.
Patients were randomly assigned to one of two treatment groups: group 1 (n=70) received 1 mL triamcinolone (40 mg/mL for injection); group 2 (n=70) received 1 mL of 0.9% injected sodium chloride. Both groups presented with similar demographic and clinical characteristics. Rate of cartilage loss was higher in the triamcinolone group vs the saline group (−0.21 vs −0.10 mm; between-group difference: −0.11 mm; 95% CI, −0.20 to −0.03 mm); the triamcinolone group also experienced higher rates of secondary cartilage damage index (mean change: −133.66 vs −72.41 μm3; between-group difference: −61.25 μm3; 95% CI, −121.78 to 0.72 μm3).
No significant differences were noted in cartilage denudation, bone marrow lesions, effusion volumes, or trabecular morphology; in a similar fashion, no significant differences were noted in subchondral tibia or bone mineral density. Superficial fibrillation was more commonly noted in the saline group (34% vs 13%; between-group difference: 21%; 95% CI, 7%-35%).
Knee pain decreases were similar in both treatment groups (−1.2 units vs 1.9 units in the triamcinolone vs saline group, respectively; between-group difference: −0.64; 95% CI, −1.6 to 0.29). The saline group reported more adverse events (63 vs 52 participants; P =.02 with 182 vs 131 events; P =.02). No significant difference in serious adverse events (P =.06) was noted.
Summary and Clinical Applicability
“The hypothesis that intra-articular corticosteroids might reduce the rate of cartilage loss and other structural manifestations of osteoarthritis was based on the recognition of the role of inflammation in its pathogenesis,” Dr McAlindon and colleagues wrote. “However, these results showed greater progression of knee cartilage volume loss and no sustained effect on intra-articular inflammation… As a proof-of-concept study, the results raise questions about the role of inflammation in osteoarthritis progression.”
- The investigators did not measure pain in the 4-week window following injections, when most benefits are known to occur
- Participants continued treatment with their usual medications throughout the trial, possibly attenuating between-group differences in symptom outcomes
- High expectations and large placebo responses may have affected investigator assessment of trial results
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 [published online May 16, 2017]. JAMA. doi:10.1001/jama.2017.5283