Ultrasound Guidance, Local Anesthetics May Reduce Placebo Response to Intra-Articular Injections for OA

Use of local anesthetics, ultrasound guidance, and poor baseline functional scores are associated with reduced odds for placebo response to intra-articular (IA) injections among patients with hip or knee osteoarthritis (OA), according to study results published in Arthritis Care Research (Hoboken).

Investigators assessed factors that may predict placebo response to IA injections for treatment of patients with hip or knee OA.

A systematic literature search and pooled individual participant data meta-analysis was conducted. Patients diagnosed with hip or knee OA who participated in placebo-controlled trials evaluating IA injections of glucocorticoids or hyaluronic acid were included in the analysis.

The main study outcome was change in pain from baseline to short-term (up to 4 weeks), mid-term (up to 12 weeks), or long-term (up to 24 weeks) follow-up. Placebo response was defined as a clinically important reduction in pain scores (at least 20%) from baseline to follow-up.

A total of 10 studies that included 621 patients who received placebo were included in the analysis.

At short-term, mid-term, and long-term follow-up 45.5%, 52.6%, and 54.7% of patients reported a placebo response 

Patients who had ultrasound-guided injections (odds ratio [OR], 0.42; 95% CI, 0.23-0.76) and received local anesthetics (OR, 0.54; 95% CI, 0.32-0.91) were less likely to respond to placebo at short-term follow-up.

Poorer functional scores reported at baseline (OR, 0.98; 95% CI, 0.96-1.00) were associated with lower odds of a placebo response at mid-term follow-up.

In contrast, trial durations of 12 to 24 weeks (OR, 10.33; 95% CI, 2.25-47.35) or longer than 24 weeks (OR, 10.68; 95% CI, 2.32-49.27) were associated with greater odds of a placebo response at mid-term follow-up.

This study was limited by its investigative nature as well as potential selection and data availability bias. Additionally, deviations from the study protocol may have occurred, as data were not available on disease laterality, comorbidities, morning stiffness, aspirate volume, and IA injection approach. Finally, inconsistencies in outcome measures across trials prevented more precise meta-analysis of the data.

The study authors concluded, “Identifying potential predictors of placebo in [IA] interventions in [OA] may help to provide guidance and modify the design for future

IA clinical trials.”

Disclosure: One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of author disclosures.