Table 3.

Summary of meta-analyses/systematic reviews of hylans/hyaluronic acids (Has) in knee osteoarthritis

References	Lo et al. [63]	Wang et al. [62]	Arrich et al. [65]	Bellamy et al. [61]	Bannuru et al. [119]	Colen et al. [64]	Rutjes et al. [36]
Total number of trials	22	20	22	76	49	74	70
Efficacy outcomes (HA versus placebo)	ES (change from baseline)	SPED, normalized to % change	Mean difference, SPID	WMD in pain during/ after exercise (VAS)	Overall pain, pain at different time points: 4, 8, 16, 20, and 24 weeks	MCID, pain	MCID, pain intensity and safety
Summary of pooled results	ES: 0.32 (P< 0.001)	SPID 7.9% (95% CI 4.1–11.7%)	WMD 10–14 week: −4.3 mm (P= 0.013) WMD 22–30 week: −7.1 mm (P= 0.013)	% change 5–13 week: +26% for pain; +23% for function	Peak ES at 8 weeks: 0.46 (95% CI 0.28–0.65)	WMD: −10.20 (95% CI −15.97 to −4.42)	ES: −0.37 (95% CI −0.46 to −0.28)
Conclusion	Small treatment effect	Significant improvement in pain	Not effective in measured outcomes	Effective treatment for pain, function, and patient global assessment at 5–13 week	Modest efficacy for knee pain	Further studies needed to determine efficacy of HA	Small, clinically irrelevant benefit

ES effect size, MCID minimal clinically important difference, SPID sum of pain intensity differences, VAS visual analog scale, WMD weighted mean difference