Addition of Mannitol to Hyaluronic Acid may Shorten Viscosupplementation Onset of Action in Patients with Knee Osteoarthritis: Post-Hoc Analysis of A Double-blind, Controlled Trial

Objectives: To compare the speed of action of three weekly intra-articular injections of a combination of hyaluronic acid and mannitol (HAnox-M) with that of hyaluronic acid alone (BioHA), in patients with knee osteoarthritis (OA). Methods: Post-hoc analysis of a randomized, double blind, controlled trial demonstrating the non-inferiority of an association HAnox-M compared to BioHA at month 6 after injections. Data from 205 patients with symptomatic knee OA (Intent-to-Treat population) were retrospectively analyzed. The primary outcome was 1 and 2 week change in the WOMAC pain subscale (0-20). The number and percentage of improved patients at week 1 and 2 were also studied, as well as the level of improvement. Results: HAnox-M and BioHA groups were not statistically different at baseline and month 6. The median WOMAC pain score at baseline was 9 in both groups. It was 6.0 and 5.0 in the HAnox-M group at Week 1 and Week 2 respectively. It was 7.0 and 6.0 in the BioHA group, namely a decrease of 1 more point in favor of HANOX, obtained from as soon as the 1st injection. At month 3 and 6 the results were identical (5.0 and 4.0 respectively) for both groups. In subjects with grade 3 joint space narrowing (N=84) the decrease of pain (SD) was significantly greater at week 3 in patients treated with HAnox-M than in those treated with Bio-HA:-4.2 (3.2) versus -2.8 (2.6) respectively (p=0.048). Conclusion: In patients with symptomatic knee osteoarthritis, addition of mannitol to HA may shorten the onset of action of viscosupplementation, chiefly in patients with advanced stage of the disease.


Florent Eymard, Marie Bossert, Roger Lecurieux, Bernard Maillet, Xavier Chevalier and Thierry Conrozier

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