Background/Purpose: Knee OA is a progressive joint disease which affects more than 250 million people worldwide. Meta-analysis (MA) has demonstrated that IA CS were more effective for pain relief than IA HA in the short term (up to 6 weeks) for knee OA. Hylan G-F 20 (Synvisc/Synvisc-One) is a high molecular weight HA indicated for the treatment of knee OA. However, the relative efficacy and safety of Hylan G-F 20 versus IA CS is not well understood due to the lack of head-to-head randomized controlled trials (RCTs). The objective of this research was to better evaluate the clinical efficacy and safety of Hylan G-F 20 versus IA CS in knee OA using both direct (pairwise) MA and network meta-analysis (NMA).

Methods: We systematically searched MEDLINE, Embase, and CENTRAL to identify RCTs on Hylan G-F 20 and IA CS compared to any treatment of knee OA. Two independent reviewers performed the literature review. Relevant study and patient characteristics (including whether ACR criteria were used for the diagnosis of knee OA) and outcome data were extracted. In a direct meta-analysis, we compared Hylan G-F 20 and IA CS using a random-effects model to estimate the pooled standardized mean difference (SMD) or mean difference (MD). In a Bayesian NMA framework, we used a random-effects or fixed-effect model based on the best fit. Efficacy was evaluated at 1, 3, and 6 (+/- 0.5) months (mo); and at the final follow-up for safety outcomes. A pain hierarchy was used to select one outcome from each study: (1) WOMAC pain (2) VAS pain (3) WOMAC, Walking Pain (4) VAS, Pain on Nominated Activity (5) VAS, Walking Pain (6) VAS, Weight-bearing Pain.

Results: Forty-five RCTs (8,047 patients) met the inclusion criteria. Of these, 26 (5,858 patients) used ACR diagnostic criteria, and 2 directly compared Hylan G-F 20 with IA CS. The NMA network consisted of 4 nodes (Hylan G-F 20, other IA HA, IA CS, and IA placebo) (see Figure 1 for an example of the network). In the direct meta-analysis, Hylan G-F 20 was superior to IA CS by 6 months based on the WOMAC index (overall score), SMD (95% Confidence Interval [Crl]): -6.08 (-10.00, -2.17). In the NMA, the analysis of change in WOMAC/VAS pain showed that Hylan G-F 20 may be equivalent to IACS in the short-term, but superior by 6 months, SMD (95% Credible Interval [Crl]): -0.13 (-0.25, -0.01) (See Table 1). In terms of the WOMAC overall score, WOMAC physical function and Lequesne Index, the results were not statistically significant at any timepoint. With regard to safety relative to IA CS, patients treated with Hylan G-F 20 had a estimated higher odds of treatment-related adverse events (AEs) (OR 2.72 [95% Crl]: 0.83, 9.75), but a lower odds of serious AEs (OR 0.53 [95% Crl]: 0.05, 2.53) and injection-site reactions (OR 0.71 [95% Crl]: 0.12, 4.45), even though the differences between the two groups were not statistical significant.

Conclusion: Overall, the results of this analysis suggest that in patients with knee OA, Hylan G-F 20 may be similar to IA CS in improving symptoms in the short term, but superior to IA CS by 6 mo. Both agents were relatively well tolerated, with no clear differences in safety while SAE seem to be more frequent with CS injections.

Table 1

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-hylan-g-f-20-versus-intra-articular-corticosteroids-in-patients-with-knee-osteoarthritis-a-systematic-literature-review-meta-analysis-and-network-meta-analysis/