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Objective
To investigate whether the number of hyaluronic acid (HA) injections in a sodium hyaluronate (Hyalgan) course of therapy alters effectiveness in reducing knee osteoarthritis (OA) pain.

Data Sources
Electronic databases, including PubMed and Embase, were searched from January 1980 until November 2015.

Study Selection
We included clinical studies that evaluated the effectiveness of a course of 3 or 5 weekly intra-articular injections of Hyalgan to treat knee OA pain. We also included clinical studies evaluating the effectiveness of a 3-week course of other Food and Drug Administration–approved HA treatments of knee OA pain. Twenty-four studies were identified, comprising 2168 study participants in 30 treated cohorts.

Data Extraction
We determined effect sizes for selected studies by extracting knee OA pain scores before and after HA or control treatments. Meta-regressions were implemented to determine whether the number of weekly injections in a course of Hyalgan therapy modified outcomes.

Data Synthesis
The pooled estimate for relief from baseline pain was ?31.4 (SE, 5.46; 95% confidence interval [CI], ?45.5 to ?17.4) with a 3-week course of Hyalgan and ?32.2 (SE, 5.25; 95% CI, ?45.6 to ?18.7) with a 5-week course of Hyalgan. Findings from the meta-analysis indicate relief of knee OA pain with a 3-week course of Hyalgan is similar to that with a 5-week course of Hyalgan (P=.916). The pooled estimate for relief from baseline pain with a 3-week course of other HA products was ?29.4 (SE, 4.98; 95% CI, ?42.2 to ?16.6), also indicating pain relief with a 3-week course of Hyalgan is similar to that with a 3-week course of other HA products (P=.696).

Conclusions
There was no statistical difference between reduction in knee OA pain with a 3-week course of Hyalgan compared with reduction in knee OA pain with a 5-week course of Hyalgan or a 3-week course of other HA products. These findings demonstrate that comparable knee OA pain relief is achieved with a 3-week course of Hyalgan and the 2 control groups.

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