Researchers found that glucocorticoid injections administered directly into the infrapatellar fat pad may not reduce knee pain or effusion synovitis volume compared with placebo in patients with inflammatory knee osteoarthritis.
In the 12-week, multicenter, double-blind, placebo-controlled trial, the researchers enrolled 60 adult patients aged 45 years or older (mean age = 65 years) with symptomatic inflammatory knee osteoarthritis (OA) across four centers in China. Baseline characteristics were well-balanced between groups. All of the participants had magnetic resonance imaging (MRI)-confirmed Hoffa synovitis and effusion synovitis and were randomly assigned to receive either a single ultrasound-guided infrapatellar fat pad (IPFP) injection of betamethasone or saline. Both groups also received intra-articular hyaluronic acid as background therapy.
The primary outcomes were changes in knee pain, measured by a 100-mm visual analog scale (VAS), and effusion synovitis volume assessed by MRI, according to the clinical trial. At 12 weeks, the participants in the treatment group experienced a mean VAS pain reduction of 39.3 mm compared with 31.4 mm in the placebo group. However, the between-group difference of 7.9 mm wasn't statistically significant. Similarly, reductions in effusion synovitis volume also didn't differ significantly between the groups.
Although the primary endpoints weren't met, several secondary and post hoc findings favored the glucocorticoid group. In post hoc analyses, the patients receiving IPFP glucocorticoid injections had greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain scores compared with those receiving placebo. MRI assessments also showed a statistically significant reduction in cartilage defect scores in the treatment group compared with in the placebo group. The clinical relevance of these findings remains uncertain because the study wasn't powered for these outcomes and the follow-up period was relatively short.
Safety outcomes were similar between the groups. One participant in each group experienced an adverse reaction, and no statistically significant differences were observed in IPFP volume, addressing concerns about potential local soft-tissue atrophy from corticosteroid exposure.
Intra-articular glucocorticoid injections are commonly used to manage knee OA symptoms, but prior studies have raised concerns about the short-lived benefits and possible cartilage loss. The rationale for targeting the IPFP stems from its role as a source of inflammatory mediators in knee OA and its close anatomical relationship with the synovium. The researchers hypothesized that injecting glucocorticoids into the IPFP might reduce inflammation while minimizing direct cartilage exposure.
The researchers noted several limitations, including the modest sample size, 12-week follow-up, use of non–contrast-enhanced MRI, and concomitant hyaluronic acid injections in both groups, which may have amplified placebo effects. Additionally, the findings may not be generalizable to patients with noninflammatory OA phenotypes.
"In conclusion, among patients with knee OA and effusion synovitis and Hoffa synovitis, glucocorticoid injections into the IPFP did not significantly alleviate pain or reduce effusion synovitis volume over 12 weeks. However, as certain post hoc outcomes favored glucocorticoid injections, further investigation may be helpful," wrote lead study author Yan Zhang, PhD, of the Clinical Research Center at Zhujiang Hospital at the Southern Medical University in China, and colleagues.
Disclosures: Senior study author Changhai Ding, PhD, of the Clinical Research Center at Zhujiang Hospital at the Southern Medical University, received grants from Guangzhou City during the study. The study authors reported no other disclosures.
Source: JAMA Network Open
