More Studies Validate HA Shots for Knee OA

A new systematic review of randomized trials has concluded that evidence modestly supports a pain-relieving effect for intra-articular hyaluronic acid (IAHA) in patients with knee osteoarthritis. The effect size of -0.39 (p<0.001) drops to -0.30 (still significant at the same p value) after controlling for publication bias.

The analysis, including 85 randomized controlled trials, was intended to explore reasons and "contextual factors" explaining discrepancies between studies of this question, said Mette Johansen of Copenhagen University Hospital's Parker Institute at the Osteoarthritis Research Society International meeting in Seattle. There was considerable inconsistency between trials, she added, and the possibility of publication bias, poor blinding of personnel, and insufficient trial size weaken the evidence. Stratifying by funding source showed no significant effect, she said.

The analysis did not include two well-known but unpublished trials that show no effect for the injections, observed David Felson MD, professor of epidemiology and medicine at Boston University School of Medicine. But including this information would not have made a substantial difference in the results, Johansen said.

"Is there a favorable effect of saline?" she asked, alluding to the substantial placebo effect for injections, at the end of her presentation. Orthopedic surgeon Stephen Trippel MD of Indiana University echoed that question in the discussion.

Sitting across the desk from the patient with knee osteoarthritis, he remarked, you can't say unequivocally that hyaluronic acid will help. Even saline injection evidently helps, but it's not approved by the FDA.

"If [IAHA] helps," he said to Rheumatology Network later, "as long as there are no adverse effects, who cares? Use it!"

A separate trial analyzing data from a very large administrative claims database has found that use of IAHA delays the time to total knee replacement.

Using data from a commercially available claims registry, Roy Altman MD, emeritus professor of rheumatology at the University of California, Los Angeles and his coworkers retrospectively analyzed records for 182,022 patients who received knee replacement surgery between 2007 and 2013.

For the 28% who had at least one preoperative course of IAHA, the time between diagnosis of OA and knee replacement surgery was significantly longer (p<0.001), compared to those who never used IAHA. More courses of injections were associated with greater delays before surgery.

The latter study was sponsored by Seikagaku Corporation, which markets hyaluronic acid for clinical uses. Altman, who participated in both studies, is a member of the Rheumatology Network Editorial Board.