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.