Reduction of the Serum Levels of a Specific Biomarker of Cartilage Degradation (Coll2-1) by Hyaluronic Acid (KARTILAGE® CROSS) Compared to Placebo in Painful Knee Osteoarthritis Patients: the EPIKART Study, a Pilot Prospective Comparative Randomized Double Blind Trial

Abstract

BackgroundViscosupplementation is a symptomatic treatment of the knee osteoarthritis based on the intra-articular injection of hyaluronic acid (IAHA). Although many studies have investigated its effect on symptoms, few clinical studies have focused on its effects on biologicals markers of cartilage metabolism. In this study, we assessed the effect of an intra-articular injection of a reticulated hyaluronic acid compound on the level of a specific biomarker of type II collagen degradation.MethodsEighty one patients with symptomatic knee osteoarthritis were included in this randomized placebo controlled trial testing a reticulated hyaluronic acid (HA) with mannitol (KARTILAGE® CROSS, 16 mg/ml, one single injection of 2.2 mL; IAHA) versus saline solution. Primary outcome was the percentage of patients with a reduction of at least 10 nmol/l of serum Coll2-1 between baseline and day 90 (D90, 3 months after injection). Secondary outcomes concerned clinical evaluation and tolerance to the study product.ResultsA significant effect of IAHA was revealed by the sensitivity analysis of the decrease in cartilage marker. In the intention-to-treat population, the percentage of patients showing a decrease in the levels of serum Coll2-1 between inclusion and D90 showed was higher in HA (56.8%) than in placebo group (28.6%; P = 0.01). The same significant difference was observed between groups in the per protocol population (57.1% vs 29.0%; P = 0.02) corresponding to all patients having received the intra-articular injection (IA), being evaluated for the primary outcome on D-10 and D90, and with no major defined deviation. No significant differences between groups were observed on the changes in function (Lequesne index) or pain and on the number of adverse events.ConclusionsThis is the first randomized double-blind placebo controlled trial showing that IA injection of reticulated HA with mannitol in knee osteoarthritis patients can reduce the serum levels of Coll2-1, a marker specific of type II collagen degradation. This finding suggests that IAHA may have a beneficial effect on cartilage degradation and that Coll2-1 could be used for the assessment of a single intra-articular treatment in clinical trials.Trial registration NCT02951585; clinicaltrial.gov. Retrospectively registered on October 28, 2016.

Hyaluronan derivative HYMOVIS® increases cartilage volume and Type II collagen turnover in osteoarthritic knee: data from MOKHA study

“…Secondly, there is evidence that urinary level of CTX-II is influenced by bone remodeling which is not demonstrated for Coll2–1 [46, 47]. Therefore, we can hypothesize that metabolic change induced by viscosupplementation in a single joint is not sufficient to influence the urinary CTX-II level resulting from bone and cartilage remodeling, while as demonstrated previously, Coll2–1 is sensitive to changes occurring in one single joint [42, 48].…”

Intra-Articular Hyaluronic Acid in the Symptomatic Treatment of Knee Osteoarthritis: A Meta-Analysis of Single-Injection Products

“…Of these, 57 included data for IA HA mono-injection 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70. At the end, 28 studies were included,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 whereas 29 studies were removed for 1 or several of the following reasons:Two studies were in combination with surgery: anterior cruc...…”

“…Seventeen did not include a WOMAC A result14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30;…”

Injections intra articulaires (IA) d'acide hyaluronique (AH) dans le traitement symptomatique de la gonarthrose : une méta-analyse des injections uniques (mono-injections)

“…Après filtrage à partir des titres et des résumés et retrait des publications en double, 112 articles complets et d'intérêt, ont été évalués pour leur éligibilité. A partir de là, 57 articles contenaient des données de mono-injection d'AH IA 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70. Au final, 28 essais ont été inclus,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, ...…”

“…3 étaient relatifs à des produits non-approuvés pour la VS en UE ou aux USA 16 , 17 , 34 17 ne proposaient aucun résultat pour le WOMAC A 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 306 comportaient des données manquantes: ni SD ni SE,35, 36, 37, 38 aucun score à l'inclusion (fixé arbitrairement à 100% = biais majeur), 39 ou données inappropriées (ratio de population pour un gain > 15 mm ou 40%) 40 …”