Efficacy and safety for IA corticosteroids and HAs are similar. The author’s approach is to perform an initial steroid injection for knee OA refractory to oral medication and adjunctive treatments based single dose convenience and more rapid clinical response.15 If this approach is successful, corticosteroid injections are continued as frequently as every 3 months.16 If the corticosteroid injection is not initially effective, or if it loses efficacy over time, the patient is switched to injected HA prior to referral for consideration of joint replacement surgery.
CHOICE OF INTRA-ARTICULAR HYALURONIC ACID
Five HA therapies of varying molecular weight are approved for the treatment of knee OA in the United States.2 Comparative efficacy data are important to consider in the selection of HA for injection. Additional factors that should influence the clinician’s choice of HA include safety and dosing schedule.
Several studies have compared the efficacy of HA preparations. A 2006 prospective study by Kotevoglu and colleagues17 randomized 59 patients to treatment with low molecular weight hyaluronan (Orthovisc), high molecular weight hyaluronan (Synvisc), or saline. At 6 months, both HA groups showed significant improvement in WOMAC pain scores compared with placebo but there was no difference between the HA groups. In a 2007 meta-analysis of hylan versus HA that included the aforementioned trial, the pooled effect size favored hylan slightly, however, heterogeneity between the studies was high.14 The most recent study compared low molecular weight HA (Hyalgan) to an intermediate weight HA (GO-ON) not available in the United States. At 6 months, GO-ON showed statistical superiority for several outcome measures, compared with Hyalgan.18
In the absence of superiority of one HA agent, factors such as safety and ease of dosing influence the selection of HA. HA injections are typically well tolerated and have a favorable safety profile.19 Uncommon side effects of HA injection include pseudoseptic inflammatory reactions and flares of crystalline arthritis as described above. The majority of HA products are given as a 3-5 injection series.2 A notable exception is Hylan G-F 20, which showed similar therapeutic effects in a single 6 mL injection compared to 3 weekly 2 mL injections.20 However, a meta-analysis by Reichenbach and colleagues14 suggested twice the risk of local reactions with Hylan G-F 20, compared with hyalruonic acid. The author has the most experience with low molecular weight products, largely due to formulary constraints and not personal preference.
COMBINATION INTRA-ARTICULAR THERAPY FOR OSTEOARTHRITIS
The potential synergy between injected anti-inflammatory agents and HA injections has been considered as a mecha¬nism to enhance therapeutic injections. Ozturk and colleagues21 performed a 1 year, randomized, single blind trial of 40 patients with knee OA. Twenty-four patients were treated with a course of HA injections at 0 and 6 months and a group of 16 patients received the same HA regimen but with the addition of 40 mg triamcinolone acetonide injected just before the first HA injection of each series.21 Both groups had the same magnitude and duration of response as assessed by standardized pain scores, however the steroid group had a more rapid response.21 There was no difference in progression of OA as assessed by magnetic resonance imaging in either group at 1 year.21
A recent meta-analysis examined the trajectory of the clinical response to injected HA to corticosteroids in knee OA. In their study, Bannuru and colleagues16 showed corticosteroids had a more rapid onset of action from baseline through week 4, compared with HA. At the fourth week, the effect of HA equaled corticosteroids, and after week 8, HA had a greater treatment effect.16 These results set the stage for further examination of the potential synergistic effect of combination injections with corticosteroids providing rapid onset relief of symptoms, and HAs providing a durable response of approximately 6 months’ duration.
The combination of NSAID and HA has also been considered as a way to enhance the effect of an injection for knee OA. In a study of 43 patients with knee osteoarthritis, 22 patients were randomized to a standard 5 injection series of HA, whereas the remaining 21 patients received 2 weekly intra-articular injections of ketorolac followed by 3 weekly injections of HA.22 At 16 weeks of follow-up, there was a statistically significant improvement in pain scores in the ketorolac plus HA group, compared with the HA group.22 Of note, the ketorolac group experienced post-injection pain for 8 hours in 5 of 21 subjects, compared with no post-injection pain in the HA group.22 No major adverse effects were observed in either group.
CONCLUSION
OA is the most common arthritis in the United States. Symptomatic treatment remains the standard of care using pharmacologic and non-pharmacologic modalities. Injections with corticosteroids or HAs are used for the treatment of knee OA when oral therapy does not provide adequate symptom control. Joint replacement surgery is reserved for those who fail more conservative therapies, including injections.