To assess, in daily practice conditions, both safety and efficacy of a single intra-articular injection of a cross-linked hyaluronic acid (HA) combined with mannitol (HANOX-M-XL) in patients with symptomatic knee osteoarthritis.


We analyzed the clinical and radiological data of 53 consecutive patients with symptomatic knee OA, treated between January and June 2016 with a single intra-articular injection of HANOX-M-XL, a viscosupplement made of a cross-linked HA (16 mg/ml) + mannitol (35 mg/
ml). The efficacy endpoints included the changes over time in the normalized (0-10) WOMAC pain, function and total and the patient’s global assessment (PGA). Patient Acceptable Symptom State (PASS) and Minimum Clinically Important Improvement (MCII) were calculated from WOMAC pain sub-score. Patient’s self assessment of treatment efficacy (0-3) and the decrease in analgesic consumption (0-5) were also obtained at the end of follow-up. Safety was assessed by recording all adverse events.


During the selected period of time 53 patients with knee OA were treated with HANOX-M-XL. The mean follow-up duration was 28 weeks (18 to 32). No patient was lost to follow-up. At baseline the mean WOMAC pain sub-score and PGA were 4.6 (1.2) and 6.0 (1.1) respectively.
The average decrease of WOMAC score over the 6 month follow-up was > 50%, versus baseline values, for both pain and function (P<0.0001).
At month 6, 82% of patients were PASS + and 86.8% had experienced improvement > MCII threshold. Three patients experienced local adverse events (increase of knee pain) after injection that resolved within 3 days.


In daily practice conditions, treatment with a single IA injection of HAnox-M-XL alleviates by more than 50% knee OA symptoms, over 6 months, in a large majority of patients, without safety concern.

Level of evidence:

Knee osteoarthritis (OA) is a major cause of pain and disability in subjects over 50, whose incidence increases dramatically in western countries [1,2]. The medical management for knee OA includes a combination of nonpharmacological and pharmacological modalities [3-6]. Among the latter viscosupplementation with intra-articular (IA) injections of high molecular weight of hyaluronic acid (HA) has been suggested to be the most efficacious treatment, as evidenced by an effectsize of 0.63 [7]. However many controversies are still remaining regarding the clinical relevance and the contextual part of this effect [8-13].


Hyaluronic acid; Viscosupplementation; Knee osteoarthritis; Mannitol; Intra-articular injection; Pilot study


PGA: Patient’s Global Assessment; MCII: Minimum Clinically Important Improvement; PASS: Patient Acceptable Symptom State



Click here to access and download the entire study.