Authors: Niamh Holmes, EMJ, London, UK
Quotation: EMJ Rheumatol. 2026;13[Suppl 1]:26-29. https://doi.org/10.33590/emjrheumatol/M96DS81R
The session ‘ESCEO Symposium: Replace of the 2017 suggestions for the usage of hyaluronic acid injections in sufferers with knee osteoarthritis: a patient-centered consultants’ consensus’ on the World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Ailments (WCO-IOF-ESCEO) 2026 introduced collectively main rheumatologists to discover the proof for intra-articular hyaluronic acid injections in osteoarthritis (OA) care.
UMBRELLA REVIEW SUPPORTS IAHA EFFICACY
Olivier Bruyère, College of Liège, Belgium, opened the dialog on the efficacy of intra-articular hyaluronic acid (IAHA) injections, showcasing the dearth of common consensus in regard to their advantages in knee OA.
Tips considerably differ for this therapy. USA pointers usually don’t advocate IAHA injections, whereas pointers from worldwide our bodies, together with the Osteoarthritis Analysis Society Worldwide (OARSI) and the European Society for Medical and Financial Elements of Osteoporosis, Osteoarthritis and Musculoskeletal Ailments (ESCEO), help their use in chosen sufferers.1,2
Bruyère outlined an umbrella evaluation that he and his group printed,3 by which the principal targets have been to make clear the effectiveness of IAHA in knee osteoarthritis utilizing proof from beforehand performed systematic critiques (SR) and meta analyses, establish the traits of SRs and meta-analyses that will clarify discrepancies in reported conclusions, and describe the outcomes that have been constant throughout research.
This umbrella evaluation adhered to the Cochrane pointers for Overviews of Opinions and the Most popular Reporting Objects for Overviews of Opinions (PRIOR) guidelines, in addition to being recorded within the Potential Register of Systematic Opinions (PROSPERO). Inclusion standards consisted of SRs of RCTs with or with out meta-analyses, assessing ache or practical efficacy outcomes in contrast with placebo, together with saline or any options. SRs together with each randomised and non-RCTs have been excluded from the evaluation, alongside scoping critiques and summary, commentaries, and narrative critiques of SRs.
He additionally outlined A Measurement Software to Assess Systematic Evaluate model 2 (AMSTAR-2) guidelines, which was used to evaluate the standard of meta-analyses and mitigate bias. The instrument categorises them into critically low, low, reasonable, and high-quality analyses.
Out of greater than 1,500 papers recognized, 22 SRs or meta-analyses have been included. Twenty of those 22 reported important advantages of IAHA for bettering affected person signs. Collective important outcomes from these research displayed 15 as having constructive conclusions, three combined, and 4 unfavourable. The AMSTAR-2 guidelines demonstrated that the 5 analyses categorised as ‘high-quality’ demonstrated statistically important advantages to the sufferers following IAHA therapy. Nevertheless, writer conclusions remained combined, with three constructive and two unfavourable interpretations. Bruyère and his group explored this discrepancy and concluded that unfavourable interpretations usually arose when there have been restrictions within the inclusion standards, such because the variety of sufferers within the RCT, or when the medical relevance of the outcomes was challenged.
Total, the umbrella examine demonstrated that high-quality SRs and meta-analyses persistently help a big impact of IAHA on ache and performance in knee osteoarthritis. Nevertheless, Bruyère argued that, as a result of responses to therapy range, affected person choice stays vital.
SAFETY PROFILE OF IAHA INJECTIONS
Ali Mobasheri, College of Oulu, Finland, talking on behalf of Emmanuel Maheu, Hôpital Saint-Antoine, Paris, France, then mentioned the efficacy and security of IAHA therapy. He highlighted the substantial placebo impact related to IAHA, noting that injections of saline, or perhaps a single puncture with out injection, could enhance OA ache.4 He argued that saline itself could act as an energetic therapy relatively than a true placebo.
An SR by Bannuru RR et al.5 studied 74 trials and 13,032 sufferers aged 45–75 years. World incidence of native hostile occasions was proven to be 8.5%, with the most typical being transcient native reactions, ache at injection web site, effusion, and arthralgia, all of which resolved spontaneously. Total security was due to this fact glorious and was corresponding to the placebo. This was supported by a Cochrane collaboration, which concluded that IAHA therapy led to extra native reactions, however fewer systemic hostile results, than systemic remedies.6
Maheu et al.7 additionally reported an 8.5% price of native post-injection reactions, consisting of ache, redness, and brief flares. Medical trials and post-marketing surveys have demonstrated related charges, whereas repeated cycles of injections don’t enhance the frequency of those reactions.
Mobasheri additionally highlighted flaws in research presenting proof towards the usage of IAHA injections, warning of deceptive knowledge the place there’s a lack of research of the plausibility of those severe hostile results. He reiterated Bruyère’s assertion that sure affected person teams could derive better profit from therapy.
He then likened criticism of IAHA security knowledge to COVID-19 anti-vaccination actions, stating that an epidemiological, contextual perspective must be thought of when taking a look at hostile occasions related to IAHA.
He concluded by highlighting the in depth security file of IAHA, demonstrating native hostile occasions corresponding to placebo injections, and only a few systemic results.
NEXT-GENERATION COMBINATION THERAPIES
Lastly, Nicholas Fuggle, College of Southampton, UK, mentioned the most recent developments in hyaluronic acid (HA) remedy for OA, particularly mixture remedy. These included combos with mannitol, sorbitol, chondroitin, polynucleotides, and tranexamic acid (TXA).
Mannitol acts as a scavenger of reactive oxygen species, lowering degradation of HA and thereby rising its residence time throughout the joint, probably prolonging the therapeutic impact. Rheological fashions have proven that, in chondrocytes from sufferers with OA, HA alone loses each its elastic and storage modulus over time, whereas with the addition of mannitol, each these properties are maintained over half-hour.8
Fuggle then introduced a examine by Maheu et al.,9 which demonstrated non-inferiority of mixed HA–mannitol remedy in contrast with HA alone in a two-arm, single-injection examine.
He then went on to stipulate the differential but related chemical construction of mannitol and sorbitol as diastereomers. Though each are six-carbon sugar alcohols, mannitol is derived from mannose, whereas sorbitol is derived from glucose. Their distinct chemical construction gives them with completely different medical purposes, as mannitol is excreted within the urine and sorbitol is metabolised by the liver.
Much like mannitol, sorbitol scavenges hydroxyl radical species. Mongkhon et al.10 demonstrated that sorbitol abrogated IL-1β-induced catabolism, irritation, and reactive oxygen species manufacturing within the joint. Moreover, baseline practical standing has been proven to foretell response to HA–sorbitol, with the underside 10th percentile for baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) perform because the strongest predictor (odds ratio: 13.81).11
He then moved on to debate chondroitin sulphate as a mixture remedy with HA. Chondroitin sulphate is thought to exert anti-inflammatory results by means of discount of nuclear issue kappa-light-chain-enhancer of activated B cell (NF-kB) activation. Given its function as a part of the cartilage matrix, it could possibly additionally contribute to hydration and elasticity.12 Chondroitin mixture remedy could due to this fact enhance the viscosity of synovial fluid, enhance HA tissue adherence, and improve rheological properties of elastic and storage modulus. Mixture remedy with chondroitin sulphate and HA considerably lowered IL-1β, IL-6, and TNF-α ranges greater than both therapy individually, whereas rising ranges of aggrecan and collagen-II.12
Fuggle subsequent mentioned polynucleotide mixture remedy. Polynucleotides are highly-purified, excessive molecular weight polymers that act as a substrate for nucleases throughout the joint, and due to this fact probably have a synergistic impact with HA. Stagni et al.13 reported a considerably better distinction in WOMAC ache scores versus baseline after 2, 6, and 12 months for polynucleotides and HA mixture remedy.
Lastly, just like mannitol mixture remedy, TXA modifies HA and protects it towards degradation. It might additionally function an anti-inflammatory issue by means of discount of IL-6 and C-reactive protein (CRP) through plasminogen-dependent and plasminogen-independent pathways.14 Potential cartilage advantages have additionally been recommended. The murine examine by Brochard et al.14 discovered symptomatic advantages of TXA-modified HA. Structural advantages have been additionally noticed, nonetheless they have been seen in each HA alone and TXA/HA mixture remedy, suggesting no extra advantage of TXA mixture remedy.
Fuggle concluded by summarising the vary of rising mixture therapies for HA. Mannitol and sorbitol combos have demonstrated non-inferiority, possible paving the best way for superiority research as the subsequent steps. Chondroitin combos, nonetheless, have been demonstrated to be efficient in single-arm research, however would require managed research to validate these findings. Trying forward, polynucleotides and TXA mixture therapies characterize novel areas of growth that will show useful in osteoarthritis administration.