Is the Rate of Responders to Hyaluronic Acid Injection for Patients with Knee Osteoarthritis Stable Over Time? Post hoc Analyses of a 6-Month Follow-Up Study.

INTRODUCTION: Recently, a study showing the non-inferiority of a single injection of sodium hyaluronate plus sorbitol (Synolis VA®) compared to hylan G-F20 (Synvisc-One®) over a 24-week period in patients with knee osteoarthritis was published. The objective of the present study is to assess if a short-term response to a single injection of sodium hyaluronate plus sorbitol can be maintained over a 6 month-period and if the maintenance of the response to treatment is dependent on the functional status at baseline. METHODS: Responders to treatment at days 28, 84, and 168 were evaluated according to the responder criteria proposed by the OMERACT-OARSI. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used to assess functional status at baseline. All analyses were adjusted for age, gender, BMI, and baseline WOMAC total score using data from the intention-to-treat (ITT) population. RESULTS: Out of the 96 patients included in the study who were receiving Synolis VA®, 59.38% were responders at day 28 according to the OMERACT/OARSI responder criteria, 59.78% at day 84, and 64.52% at day 168. Among the responders at D28, the probability of being responder at D84 and D168 was significantly higher than among non-responders, with corresponding odds ratio (95% CI) of 2.85 (1.07-7.59) and 7.28 (2.53-20.93), respectively. Patients with a poorer physical function at baseline were more likely to respond to the treatment at all time points, compared to those with a better physical function (OR 3.74 [1.37-10.21]). CONCLUSIONS: An early response of a single injection of sodium hyaluronate plus sorbitol is predictive of long-term response, up to 24 weeks. Patients with a poorer physical function may best benefit from the treatment.

Assessment of the Response Profile to Hyaluronic Acid Plus Sorbitol Injection in Patients with Knee Osteoarthritis: Post-Hoc Analysis of a 6-Month Randomized Controlled Trial.

In a previous randomized trial, the non-inferiority of two hyaluronic acid injections (Synolis VA versus Synvisc-One) was assessed in patients with knee OA, with a response rate of 79% for Synolis VA. To assess whether a responder profile could be established for this treatment modality, we used the Synolis VA arm of a published 6-month prospective, multicenter, comparative, randomized, double-blinded trial. At baseline and during the study, pain and function were assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Ninety-six subjects from the intention-to-treat trial were included in the analysis. The 6-month change of WOMAC Pain with Synolis VA was not associated with any baseline clinical data. However, the change in WOMAC Function was significantly associated with its baseline level, even after adjustment for potential confounding variables (p = 0.028), i.e., a poorer physical function at baseline was associated with a better response. In conclusion, in addition to the high absolute response rate to Synolis VA, the probability of success is even increased if administered in patients with more limited physical function at baseline. Further research with other potential confounding clinical variables is warranted in order to better applicate the concept of personalized medicine.

Non-Inferiority of a Single Injection of Sodium Hyaluronate Plus Sorbitol to Hylan G-F20: A 6-Month Randomized Controlled Trial.

INTRODUCTION: Several viscosupplement treatments are available for patients suffering from painful osteoarthritis (OA) of the knee, but few comparative clinical trials have been conducted. The primary objective of the trial was to demonstrate the non-inferiority of Synolis VA (80 mg hyaluronic acid and 160 mg sorbitol) (Group HA1) to Synvisc-One (48 mg hylan GF-20) (Group HA2) at Day 168 in terms of pain relief efficacy in patients with knee OA (Kellgren and Lawrence radiological stage II or III) in whom oral treatment with analgesics, NSAIDs or weak opioids provided insufficient clinical responses or were poorly tolerated. METHODS: This was a prospective, multicentre, comparative, randomized, double-blinded trial comparing the two previously indicated viscosupplements, HA1 and HA2. The average VAS pain score (1-100) was 62.5 at baseline (Day 0). The patients were randomized into two parallel groups at Day 0 and followed until Day 168. They received one injection of either HA1 or HA2. The primary end point was the evolution of the Western Ontario and McMaster University (WOMAC) pain index at D168 in the groups. One of the secondary end points was the daily assessment of this index by the patient for 7 days following the injection and thereafter at Day 14. The other secondary end points were the WOMAC pain, stiffness, function and total scores assessed at Day 28, Day 84 and Day 168. At Day 168, efficacy and satisfaction were assessed by the evaluator and by the patient using a Likert scale (7 points). Moreover, the number of strict responders in each group was evaluated according to the The Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT) criteria (OMERACT-OARSI). The per protocol (PP) population was used for the primary analysis. RESULTS: A total of 202 patients were randomized. The patients were predominantly female (66%). The median age of the whole population was 65 years, and the median body mass index was 27.4 kg/m2. No statistically significant differences between the two treatment groups were observed for any of the demographic criteria. At Day 168, 197 had had no protocol violations (94 in the HA1 group and 103 in the HA2 group). The WOMAC pain score decreased in the two groups: - 29.2 ± 24.1 (SD) in the HA1 group and - 31.6 ± 25.5 (SD) in the HA2 group, confirming the non-inferiority of Synolis VA (P = 0.57 for the difference between groups). Regarding the secondary end points, no significant difference was observed at Day 14, Day 28, Day 84 or Day 168 for all the outcomes except stiffness at Day 28 (P = in favour of treatment received in HA2). The rate of responders was comparable between the two groups: 79% for HA1 and 77% for HA2. Both products were well tolerated. Serious adverse events were reported by four patients in the HA1 group and 3 in the HA2 group. CONCLUSION: In this trial, we confirmed the non-inferiority of Synolis VA compared to Synvisc-One at Day 168 according to the WOMAC pain score. Safety was satisfying and comparable in the two groups. TRIAL REGISTRATION: 2017-A00034-49.