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Three Part Question

In [adults with OA knee], is [Intra-articular Hyaluronic Acid (HA) injection better than Corticosteroid (CS) injection] in [reducing pain and improving function]?

Clinical Scenario

A 52 year old male presents to the orthopaedic knee service with gradual onset of knee pain and effusion. He finds walking is now limited to 2 hrs and he struggles to play a full round of golf. Knee X-ray findings confirm moderate signs of degenerative joint disease. He is not yet at the stage to consider a joint replacement. He has tried physiotherapy and relative rest but now is keen for an ‘injection’. Should he be offered a corticosteroid or hyaluronic acid injection?

Search Strategy

Using the Health Databases Search via the NHS Library interface (library.nhs.uk) the following databases were interrogated: AMED (1985-present), BNI (1992 – present), CINAHL (1981-present), EMBASE (1974-present), MEDLINE (1946-present). Searches were also carried out in the Cochrane Library and the PEDro database. Internal References from papers.
{knee} AND {OA OR osteoarthritis} AND {corticosteroid} AND {hyaluron*} AND {Systematic* OR Meta*}

Search Outcome

22 papers found. 2 meta-analyses chosen. 19 excluded as they were not systematic reviews or meta-analyses. One was excluded due to directly using one of the chosen references as its data source (Same author repeating previous analyses of results).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Wang et al, 2015 China	Pooled from 7 RCT: 583 patients (222 males, 361 females) with knee OA. Mean ages ranged from 49.5 to 70.5 years. Intervention: intra articular injection of either CS or HA. Follow up ranged from 12 weeks to 6 months	Meta-analysis	VAS	at 1/12 CS better than HA	No comparison to placebo in RCT studies 1 study is methodologically weak (JADAD and PEDro - Used Jadad scoring system initially, which is criticised as being simplistic.) Variety of HA and CS agents evaluated.
			VAS	at 3/12 HA better than CS
			VAS	at 6/12 HA better than CS
			Lequesne	No difference at 3/12
			KSS	No difference at 3/12
			Maximum Flexion	No difference at 3/12
			Adverse Effects	No difference at 3/12
Bannaru et al 2009 USA	Pooled from 7 RCT (published 1987-2004): 606 patients (610 knees). HA group: 312 (101 males and 211 females) CS group:294 (298 knees, 99 male and 195 females) Follow up at 2,4,12, and 26 weeks	Systematic Review and Meta-Analysis	Pooled Effect Size	at 2/52 CS better than HA	Degree of OA for participants? Repeated weekly injections, reflects practice? Also, when does the follow up period start? After all injections? Differing drugs used and treatment protocols Are results statistically significant? HA sponsorship Trial quality wasn’t tested with PEDRO or equivalent. No placebo, are long term effects of HA better than nothing? Allowed participants to use pain medication in 6 studies
			Pooled Effect Size	at 4/52 No difference
			Pooled Effect Size	at 8/52 HA better than CS
			Pooled Effect Size	at 12/52 HA better than CS
			Pooled Effect Size	at 26/52 HA better than CS

Comment(s)

These are good meta–analyses looking at published RCT’s where HA was compared with CS in the treatment of symptomatic OA of the knee in adults. Both groups of authors evaluated the quality of the papers by assessing them against the PEDro quality score and with Wang et al, also the JADAD score. Both author groups requested further data from authors if there was not adequate data in the studies. Both papers tested for publication bias.

Clinical Bottom Line

Corticosteroid injection is more effective at relieving pain within the first month after administration but then following that, Hyaluronic acid injection gives better symptomatic benefit up to 6 months after administration. There were few adverse effects documented with either injection.

References

1. Wang, F. and He, X., Intra-articular hyaluronic acid and corticosteroids in the treatment of knee osteoarthritis: A meta‑analysis Experimental and Therapeutic Medicine 2015; 9, pp.493-500
2. Bannuru, R.R., Natov,N.S., Obadan, I.E., Price, L.L., Schmid, C.H., and McAindon, T.E. Therapeutic Trajectory of Hyaluronic Acid Versus Corticosteroids in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis Arthritis & Rheumatism (Arthritis Care & Research) 2009; 61(12), pp.1704-11