Bernard Maillet

Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO2) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: A research study part of the Biovisco study

To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2‐1 and Coll2‐1 NO2 in knee osteoarthritic patients after viscosupplementation (VS). Fifty‐one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra‐articular injections of 2 ml of hyaluronic acid (Hylan GF‐20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2‐1 and Coll2‐1 NO2 were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty‐five patients were analyzed. The serum concentrations of Coll2‐1 and Coll2‐1 NO2 were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2‐1 was significantly lower at baseline in responders than in non‐responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G‐20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2‐1 appeared to be a predictive factor for response to treatment.

Early effect of hyaluronic acid intra-articular injections on serum and urine biomarkers in patients with knee osteoarthritis: An open-label observational prospective study†

The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty‐one patients with unilateral symptomatic K‐OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D‐15 patients were examined and X‐rays performed, to exclude patients with bilateral K‐OA, or those with more than three symptomatic OA joints. From 15 days (D‐15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D‐15, D1, D30, and D90. S‐C2C, S‐Cartilage oligomeric matrix protein, S‐HA, S‐CS 846 epitope, S‐type II collagen propeptide, and U‐type II collagen C telopeptide (U‐CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty‐five patients were analyzed. Between D‐15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U‐CTX II/creat (p = 0.006). Between D1 and D90: U‐CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U‐CTX II/creat variation. U‐CTX II and S‐HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U‐CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation.

Predictors of response to viscosupplementation in patients with hip osteoarthritis: results of a prospective, observational, multicentre, open-label, pilot study

BackgroundTo identify predictive factors of response to viscosupplementation (VS) in patients with hip osteoarthritis (HOA).MethodsProspective, multicentre, open-label trial, achieved in daily practice conditions. Patients with HOA were treated with a single intra-articular injection of a cross-linked hyaluronic acid combined with mannitol (HAnox-M-XL), using imaging guidance. WOMAC pain and function scores and patient global assessment (PGA) were assessed at baseline and day 90. Improvement, satisfaction and efficacy were self-assessed at day 90.Hip radiographs at baseline were scored using Kellgren-Lawrence grade and Osteoarthritis Research Society International (OARSI) score. Associations between clinical and radiological features and response to VS (pain improvement > 50% at day 90) were assessed in univariate analysis, and then using logistic regression, adjusted for confounding factors.ResultsThe intent-to-treat (ITT) population included 97 patients (57 females, mean age 63). Ninety completed the follow-up and 80 had full clinical and radiological data. Response to VS was achieved in 47.8% of patients. In univariate analysis, the only clinical outcome statistically and negatively related to response was PGA at baseline (p = 0.047). Radiologically, response to VS was negatively correlated with joint space narrowing (JSN) score (JSN < 2 vs. JSN ≥ 2, p = 0.01) and was related to the patterns of femoral head migration (p = 0.008). In multivariate analysis, only JSN grade (p = 0.03) remained significantly related to a poor response.ConclusionThis pilot study, which needs further confirmation by larger scale trials, suggests that radiological features might be of importance for the decision of VS in patients with HOA.Trial registration numberID RCB N°2013-A00165-40. Registered 31 January 2013.

Safety and Predictive Factors of Short-Term Efficacy of a Single Injection of Mannitol-Modified Cross-Linked Hyaluronic Acid in Patients with Trapeziometacarpal Osteoarthritis. Results of a Multicentre Prospective Open-Label Pilot Study (INSTINCT Trial):

Purpose: To assess safety and search predictive factors of efficacy of a single intra-articular injection of a mannitol-modified hyaluronic acid (HA) viscosupplement, in patients having trapeziometacarpal (TMC) osteoarthritis (OA). Methods: Patients with symptomatic TMC OA, not adequately relieved by analgesic therapy and/or by the use of a thumb splint, were included in a 3-month prospective multicentre open-label trial. All underwent plain radiographs with the Kapandji incidences allowing the Dell radiological grade assessment (1-4). Primary end point was the variation between injection (D0) and day 90 (D90) of the thumb pain (11-point Likert scale). Treatment consisted in a single injection of 0.6 to 1 mL of a viscosupplement made of a cross-linked HA combined with mannitol. All injections were performed under imaging guidance. Predictive factors of pain decrease were studied in univariate and multivariate analysis. Results: A total of 122 patients (76% women, mean age 60, mean disease duration 36 months) were included and 120 (98%) were assessed at 3 months. The TMC OA was of Dell’s grade 1, 2, 3, and 4 in 23%, 36.8%, 36.8%, and 3.5% of cases, respectively. At D0, the average (SD) pain level was 6.5 ± 1.6 without significant difference between Dell groups (P = .21). At day 90, pain decreased from 6.5 ± 1.6 to 3.9 ± 2.5 (difference −2.7 ± 2.5; −42%; P < .0001) without significant difference between Dell grade (P = .055), despite a seemingly smaller number of responders in stage 2 patients. The average analgesic consumption decreased in more than 1 out of 2 patients. In multivariate analysis, no predictor of response was identified. There was no safety issue. All adverse events (11%) were transient increase in pain during or following HA administration and resolved without sequel within 1 to 7 days. Conclusions: This study suggests that a single course of HANOX-M-XL injection is effective in relieving pain in patients with TMC OA, without safety concern. Patients with advanced stage of OA benefit the treatment as much as those with mild or moderate OA.

Hip Inflammation MRI Scoring System (HIMRISS) to predict response to hyaluronic acid injection in hip osteoarthritis

OBJECTIVE To assess predictors of response, according to hip MRI inflammatory scoring system (HIMRISS), in a sample of patients with hip osteoarthritis (OA) treated by hyaluronic acid (HA) injection. METHOD Sixty patients with hip OA were included. Clinical outcomes were assessed at baseline and three months after HA injection by WOMAC. On hip MRI performed before HA injection, bone marrow lesion (BML) and synovitis were assessed by HIMRISS by four readers. The inter-reader reliability of HIMRISS was for HIMRISS total, acetabular BML, femoral BML and synovitis-effusion respectively 0.86, 0.64, 0.83 and 0.78. Associations between MRI features and clinical data were assessed. Logistic regression (univariate and multivariate) was used to explore associations between MRI features and response to HA injection, according to WOMAC50 response at three months. RESULTS In total, 45.5% of patients met WOMAC50 response. Five adverse events were reported. At baseline, WOMAC function correlated significantly to HIMRISS synovitis-effusion (r=0.27, P=0.03). In univariate analysis, BML femoral according to binary assessment (P=0.025), HIMRISS BML femoral (P=0.0038), HIMRISS BML acetabular (P=0.042), HIMRISS total (P=0.0092) were associated negatively with WOMAC50 response. In multivariate analysis, adjusted for age and BMI, HIMRISS femoral BML (P=0.02) and HIMRISS total (P=0.016) were negatively associated with response. At a HIMRISS threshold of<15, 82% of patients were responders, with specificity SP=0.97, sensitivity SN=0.39, and positive and negative predictive values of 0.91 and 0.64, respectively. CONCLUSION HIMRISS is reliable for total scores and sub-domains. It permits identification of responders to HA injection in hip OA patients.

Addition of Mannitol to Hyaluronic Acid may Shorten ViscosupplementationOnset of Action in Patients with Knee Osteoarthritis: Post-Hoc Analysis of ADouble-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.