Standardized Follow-up of Patients with Symptomatic Knee Osteoarthritis Treated with a Single Intra-articular Injection of a Combination of Cross-Linked Hyaluronic Acid and Mannitol

OBJECTIVES The objective of this study is to obtain pilot data from daily practice conditions of a viscosupplement made of a cross-linked high-molecular-weight hyaluronic acid (HA) combined with mannitol in patients with knee osteoarthritis (KOA). METHODS The data of 40 consecutive patients, 29 women and 11 men, who were prospectively followed up for 6 months, using a standardized procedure, were retrospectively analyzed. All patients have received a single intra-articular injection of HAnox-M-XL (4.4 mL), viscosupplement made of a cross-linked HA (16 mg/mL) + mannitol (35 mg/mL), in the target knee. The primary outcome was safety. The secondary end points included 3- and 6-month change in the WOMAC pain (0-50) and WOMAC total (0-240) and patient's global assessment (PGA). Patient's self-assessment of treatment efficacy (0-3) and analgesic consumption were obtained at months 3 and 6. An intent-to-treat analysis was performed. RESULTS Mean (SD) age was 60.7 (13.9) years, and mean BMI was 28.6 (5.0). Kellgren-Lawrence radiological grade was I/II and III/IV in 13 and 27 of the subjects, respectively. The average WOMAC pain and WOMAC total scores at baseline were 21.5 (9.8) and 89.9 (42.8), respectively. Thirty-nine patients completed the follow-up. HAnox-M-XL was well tolerated; two patients experienced knee pain after injection, which resolved within three days. No treatment-related severe adverse event was reported. Mean (SD) variations in WOMAC pain and WOMAC total scores were -8.2 (8.9) and -38.4 (35.6), respectively, at month 6 (P = 0.001). PGA decreased from 5.5 (2.0) to 3.0 (2.2) (P = 0.006). Efficacy was rated as good or very good in 76.9% of the cases. Most of the regular analgesics users decreased their consumption. CONCLUSION Treatment with one injection of 4.4 mL HAnox-M-XL is effective to alleviate KOA symptoms over six months, without safety concern. Controlled trials are needed to confirm these pilot data.