Hyaluronan derivative HYMOVIS® increases cartilage volume and type ii collagen turnover in osteoarhritic knee: Data from MOKHA study

Henrotin, Yves; Bannuru, R.; Malaise, Michel; Ea, H.-K.; Confavreux, C.; Bentin, J.; Urbin-Choffray, D.; Conrozier, T.; Brasseur, J.-P.; Thomas, P.; Hick, A.-C.; Marinello, A.; Giordan, N.; Richette, P.

doi:10.1186/s12891-019-2667-0

Article (Scientific journals)

Hyaluronan derivative HYMOVIS® increases cartilage volume and type ii collagen turnover in osteoarhritic knee: Data from MOKHA study

Henrotin, Yves; Bannuru, R.; Malaise, Michel et al.

2019 • In BMC Musculoskeletal Disorders, 20 (1)

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/246794

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10.1186/s12891-019-2667-0

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31215422

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Keywords :

Biomarkers; Cartilage; Hyaluronic acid; Osteoarthritis

Abstract :

[en] Background: The objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger placebo-controlled clinical trial studying the disease-modifying activity of this treatment. Methods: Forty six patients with symptomatic knee Osteoarthritis (OA) were enrolled in this open-label, prospective, multicenter, pilot study. Patients received two treatment cycles of intra-articular injections (3 mL) of HYMOVIS® (8 mg/mL of hyaluronic acid hexadecylamide) at 6 months interval. Each treatment cycle involved two intra-articular injections 1 week apart. All patients had Magnetic Resonance Imaging (MRI) of the target knee at baseline and 1 year, and blood samples to assess joint biomarkers. The primary outcome was the change in type II collagen-specific biomarkers (Coll2-1, Coll2-1NO2 and CTX-II) after HYMOVIS® treatment versus baseline. Secondary endpoints included levels changes in aggrecan chondroitin sulfate 846 epitope (CS-846), Cartilage Oligomeric Matrix Protein (COMP), procollagen type II N-terminal propeptide (PIIANP), Matrix Metalloprotease (MMP)-3, Myeloperoxidase (MPO) and Interleukin (IL)-6 serum biomarkers, the ratio Coll2-1/PIIANP, CTX-II/PIIANP, variation of MRI cartilage volume, and Knee injury and Osteoarthritis Outcome Score (KOOS) index. Results: Coll2-1 serum levels significantly increased overtime while Coll2-1NO2 levels were only increased at D360. Serum PIIANP levels also progressively and significantly enhanced with time. In contrast, other serum biomarker levels including CTX-II, CS-846, COMP, MMP-3, MPO or IL-6 did not change significantly overtime. Interestingly, the ratios Coll2-1/PIIANP and CTX-II/PIIANP decreased, indicating a decrease of cartilage catabolism. Compared to baseline value, MRI cartilage volume and thickness increased in lateral femoral and lateral trochlea compartments and not in medial compartment. These results, in addition to an improvement of T2 mapping score suggest a positive structural effect of the product. Interestingly, WORMS effusion score, an indicator of synovitis, significantly decreased. Finally, global KOOS score and subscales significantly increased overtime while pain at rest, walking pain and patients or investigators global assessment of disease activity decreased. The safety profile was favorable with a low incidence of injection-site pain. Conclusion: HYMOVIS®, a well-tolerated intra-articular treatment, significantly enhanced type II collagen turnover as suggested by the increase in Coll2-1 and PIIANP levels and cartilage volume observed by MRI in lateral knee compartment. Importantly, this study provides critical information for the design of a larger phase III clinical trial investigating Disease Modifying effect of HYMOVIS®. Trial registration: http://www.isrctn.com/ISRCTN12227846 11/02/2015. © 2019 The Author(s).

Disciplines :

Rheumatology

Author, co-author :

Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartilage (U.R.O.C.)

Bannuru, R.; Center for Treatment Comparison and Integrative Analysis, Division of Rheumatology, Tufts Medical Center, Boston, MA, United States

Malaise, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Rhumatologie

Ea, H.-K.; Service de Rhumatologie - Centre Viggo Petersen, Hôpital Lariboisière, Paris, France

Confavreux, C.; Department of Rheumatology, Hospices Civils de Lyon, Lyon, France

Bentin, J.; Service de Rhumatologie, CHU Brugmann, Bruxelles, Belgium

Urbin-Choffray, D.; Service de Médecine Physique, CHR Citadelle, Liège, Belgium

Conrozier, T.; Service de Rhumatologie, Hôpital Nord Franche-Comté, Trévenans, France

Brasseur, J.-P.; Service de Rhumatologie, CHU UCL Namur, Site de Godinne, Yvoir, Belgium

Thomas, P.; Service de Rhumatologie, CHR Metz-Thionville, Hôpital Bel Air, Thionville, France

More authors (4 more)

Language :

English

Title :

Hyaluronan derivative HYMOVIS® increases cartilage volume and type ii collagen turnover in osteoarhritic knee: Data from MOKHA study

Publication date :

2019

Journal title :

BMC Musculoskeletal Disorders

eISSN :

1471-2474

Publisher :

BioMed Central Ltd.

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

FP7 IDEAS-ERC: 305815
ERC - European Research Council
Fidia Farmaceutici

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