Intra-Articular Hyaluronic Acid Injections for Knee Osteoarthritis

In patients with osteoarthritis (OA) of the knee, do intraarticular hyaluronic acid injections decrease costs and delay the need for total knee arthroplasty (TKA)?

Intra-articular hyaluronic acid injections delay TKA by 299 to 370 days, with multiple courses delaying surgery up to 59 months. Approximately 84% of patients receiving these injections do not undergo TKA within 2 years. (Strength of Recommendation [SOR]: B, a systematic review and meta-analysis and a systematic review without quality measures.) Among patients with knee OA, intra-articular hyaluronic acid injections decrease use of nonsteroidal anti-inflammatory drugs, steroid injections, and opioid medications. This can potentially save patients thousands of dollars and the health care system billions of dollars. (SOR: B, systematic review of economic retrospective reviews.)

A 2022 systematic review and meta-analysis of 22 retrospective and three prospective cohort studies (N = 2,824,401; patients ages 55.1 ± 12.8 to 70.5 ± 9.2 years) evaluated whether intraarticular hyaluronic acid injections delayed TKA. In seven studies that included the primary outcome of time from diagnosis of knee OA to TKA, the median time was 16 to 30 months for those who received intra-articular hyaluronic acid injection vs 4 to 12 months for those who did not (P < .001). The meta-analysis included four studies showing a mean time of 614 ± 456 days from knee OA diagnosis to TKA for those receiving intra-articular injections vs 234 ± 377 days for those who did not. The mean difference was 299 days (95% CI, 250–348 days). The effect size for intra-articular hyaluronic acid injection was 0.57 (95% CI, 0.38–0.76), which is considered a moderate treatment effect.¹

The secondary outcome of time from intra-articular hyaluronic acid injection to TKA was included in seven studies and ranged from 7 to 36 months, with a pooled mean time of 14.3 ± 11.1 months. However, only one study (n = 20) included a control group. Limitations of this study included limited consideration of comorbidities, different practices for intra-articular hyaluronic acid injection in different countries, and the fact that time of OA diagnosis is not the same as time of symptom onset.

A 2021 systematic review summarized economic evaluations of intra-articular hyaluronic acid for knee OA in the United States. It included 21 studies, and five examined the effect of intra-articular hyaluronic acid on time to TKA, eight evaluated the use of health care resources, and eight studied cost-effectiveness.² Studies that assessed the time from intraarticular hyaluronic acid injection to TKA showed that injection was associated with longer time to TKA. One study found the median time to TKA for those receiving injections was more than four times longer than the time for those who did not (484 days vs 114 days; P < .0001). Other studies showed that multiple courses of intra-articular hyaluronic acid injection led to longer time to TKA. One study found that TKA was delayed by 21 months with one course and by 59 months with five or more courses. In another study, one, two, three, four, and five or more courses led to delays of 376, 618, 777, 856, and 972 days, respectively.