Severe Acute Localized Reactions Following Intra-Articular Hyaluronic Acid Injections in Knee Osteoarthritis

Abstract

Objective Concerns have been raised about severe acute localized reactions (SALR) following intra-articular (IA) hyaluronic acid (HA) injections for knee osteoarthritis (OA). We compared surrogate SALR measures between hylan G-F 20 and non-hylan G-F 20 HA patients and evaluated corresponding SALR risk factors for hylan G-F 20 patients. Design Knee OA patients were identified from the Optum Clinformatics dataset (January 2006 to June 2016), stratified into hylan G-F 20 and non-hylan G-F 20 HA users. Occurrences of surrogate SALR measures including inflammation/infection, intra-articular corticosteroid (CS) injections, arthrocentesis/aspiration, and office visits were evaluated within 3 days of HA use. Risk factors were evaluated using logistic regression. Results The cohort involved 748,428 HA patients (23.2% in the hylan G-F 20 group). Inflammation/infection rate was 0.001% for hylan G-F 20 and 0.002% for non-hylan G-F 20 HA groups. Risk of CS injection (any diagnosis) was greater for hylan G-F 20 patients by 28% ( P < 0.001). Combined rates of CS injection and arthrocentesis/aspiration (any diagnosis) were comparable for both groups (hylan G-F 20, 2.2%; non-hylan G-F 20 HA, 2.6%). The risk of any visit or studied responses was lower for the hylan G-F 20 cohort by 12% ( P < 0.001). Clinical characteristics, such as CS injections within 1 week before HA and fluoroscopic imaging, were associated with the outcomes. Conclusions The diagnosis of inflammations or infections within 3 days of the HA injection was extremely rare. The overall risk of surrogate SALR measures was similar for hylan G-F 20 and non-hylan G-F 20 HA patients.

Risk of Severe Acute Localized Reactions for Different Intraarticular Hyaluronic Acid Knee Injections in a Real-World Setting

“…Previously published findings from the same database as the present study showed that there was no statistically significant difference in SALRs between hylan and non-hylan G-F 20 products. 25 Those findings suggested that crosslinking or avian-derived HA may not play a role in SALRs as had been previously hypothesized, but the analysis was not stratified to be able to provide further comparisons of different products.…”

“…In claims database study of almost 750,000 HA patients, the diagnosis of inflammation or infection within 3 days of a HA injection was extremely rare for both hylan G-F 20 (0.001%) and non-hylan G-F 20 (0.002%) HA patients. 25 The study also concluded that the overall risk of surrogate severe acute localized reaction measures was similar for hylan G-F 20 and non-hylan G-F 20 HA patients. However, the non-hylan G-F 20 HA group was not stratified based on the specific HA product that was used, thus not allowing any further comparisons with hylan G-F 20.…”

Intra-articular Injections of Cross-linked Hyaluronic Acid in Japanese Patients with Symptomatic Osteoarthritis of the Hip

“…10,29) It is suspected that chemically cross-linked HA molecules are the cause of arthritis 36) or that the accumulation of HA results in sensitization 37) ; nonetheless, there are reports that these reactions can occur after the first HA injection 38) or after injection of HAs other than Hylan G-F 20, and the cause of this has not yet been clarified. 39) Considering these reports, it is considered that Hylan G-F 20 can be used safely, but it must be used with caution because any acute inflammatory reaction may require differentiation from septic arthritis. Data from the national registry of Iceland indicate that the infection rate after hip injection is estimated to be 0.037%.…”

Current and novel theranostic modalities for knee osteoarthritis

“…However, some allergic side effects have been seen in HA injection related to the origin of this product (animal derived glycosaminoglycan, such as cockscomb tissue). Pain and swelling after injection could be related to the high molecular weight and different pharmaceutical formulations of HA [60]. The other major challenge of treatment with HA is the multiple injection requirement in order to get to the desired efficiency.…”