Hyaluronic Acid
Hyaluronic acid intra-articular injection(s) is not recommended for routine use in the treatment of symptomatic osteoarthritis of the knee.

Rationale

The Hyaluronic Acid recommendation was downgraded one level due to a lack of generalized results.

Twenty-eight studies (17 high-strength (Chevalier 2010, Petterson 2018, Maheu 2019, Neustadt 2005, Baltzer 2009, Lundsgaard 2008, Altman 2004, Huang 2011, van der Weergen 2015, Altman 2009, Day 2004, Jorgensen 2010, Henrotin 2017, Henderson 1994, Hangody 2018, Saccomanno 2016, Altman 1998)  and 11 moderate-strength (Jubb 2003, Navarro-Sarabia 2011, Farr 2019, Kahan 2003, Kahan 2003, Karlsson 2002, Hermans 2019, Huskisson 1999, Heybeli 2008, Petrella 2006, Takamura 2018, Wobig 1998)) assessed intraarticular hyaluronic acid (HA) injections when compared to controls. A comparison of patients from these studies and from studies validating the MCIDs were used to judge clinical significance. Results revealed that patients were demographically comparable for WOMAC and VAS pain as well as WOMAC function based on age, baseline pain scores, BMI, weight, and gender. Meta-analysis in meaningfully important difference (MID) units showed that the effect was less than 0.5 MID units, indicating a low likelihood that an appreciable number of patients achieved clinically important benefits after intraarticular HA injection (Guyatt et al.). When we differentiated high- versus low- molecular weight viscosupplementation (three high, two moderate and two low quality studies), our analyses demonstrated no significant differences among different viscosupplementation formulations. Crosslinking features of the viscosupplemtation product was assessed in two high quality studies. In patients with OA, there was no difference between cross-linked and non-cross-linked HA.

Some studies demonstrated a statistical benefit with the use of HA but could not reach the significance for a minimally clinical meaningful difference, leading to the conclusion that viscosupplementation can represent a viable option for some patients that failed other treatments when appropriately indicated.  The number needed to treat to see a tangible benefit from HA was 17 patients. Furthermore, this difference was most evident at 6 weeks and 3 months. Most of the studies that exist in the literature evaluate low to moderate arthritic knees (Kellgren Lawrence of I-III) with worse results in patients with severely affected knees (KL IV).

The 2013 edition of this guideline strongly recommended against the use of viscosupplementation. In contrast to this updated version, the 2021 version found that statistically significant improvements were associated with high-molecular cross-linked hyaluronic acid but when compared to mid-range molecular weight, statistical significance was not maintained. This newer analysis did not demonstrate clinically relevant differences when compared to controls. However, as previous research reported benefits in their use, the group felt that a specific subset of patients might benefit from its use.

Benefits/Harms of Implementation

There are no major known or anticipated harms associated with implementing this recommendation.

Cost Effectiveness/Resource Utilization

The cost-effectiveness of different intra-articular therapies is still to be determined, in comparison to other treatment strategies and among different intra-articular alternatives.

Acceptability

Currently intra-articular treatments are commonly utilized approach in treating symptomatic knee osteoarthritis, hence there should be no issues implementing this recommendation as it does not influence a major change in clinical practice, and it provides further evidence to support and guide these practices.

Feasibility

These recommendations do not interfere with other interventions or clinical practice therefore it is deemed very feasible in patients with symptomatic knee osteoarthritis.

Future Research

Future research in this area should embrace detailed osteoarthritis characterization including sub-group analyses and osteoarthrosis severity stratification. Furthermore, using clinically relevant outcomes and controls for bias are warranted along with cost-effectiveness analysis.