Philippe Coste

OARSI/OMERACT Initiative to Define States of Severity and Indication for Joint Replacement in Hip and Knee Osteoarthritis. An OMERACT 10 Special Interest Group

Objective. To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of “need for joint replacement surgery,” for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). Methods. New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons’ indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. Results. In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%–12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0–100) + physical function (0–100) > 80]. Conclusion. These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define “nonresponders” to disease-modifying drugs in OA clinical trials.

Randomised, controlled trial of avocado–soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study

Objective To assess the ability of avocado–soybean unsaponifiable—Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Methods Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of ‘progressors’ (JSW loss≥0.5 mm) between groups. Results 399 patients were randomised (345 kept in the FAS), aged 62 (35–84) years, 54% women, mean body mass index 27 (SD 4) kg/m2, mean symptom duration 4 (SD 5) years, 0–100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (−0.638 mm vs −0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. Conclusions 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment. Trial registration number on ClinicalTrial.gov NCT01062737

Validation of the KOFUS (Knee Osteoarthritis Flare-Ups Score)

OBJECTIVE To develop a diagnostic score for knee osteoarthritis flare-ups and to evaluate its sensitivity and specificity. METHODS We used two epidemiological databases built using the same methodology. One database was from a general-practice study and served to develop the score, whereas the other was from a rheumatology study and served to validate the score. Physicians determined the flare-up status of each patient. The rheumatologist diagnosis was the reference standard. Logistic regression was performed to identify factors significantly associated with having a flare-up. RESULTS Of the 6085 patients in the general-practice database, 52.3% had a knee osteoarthritis flare-up. The score was built by assigning points to features that were present, with a weighting system based on the odds ratio of each feature for having a flare-up (0, feature absent; 1, morning stiffness for longer than 20 min; 2, pain causing nocturnal awakenings and knee effusion; 3, limping, joint swelling, and increased warmth over the knee). The score could range from 0 to 14. The receiver-operating characteristic curve showed that 7 was the best cutoff for diagnosing a flare-up. In the rheumatologist database, the numbers of patients having a flare-up were 274 (46.4%) based on the score and 270 (45.7%) based on the rheumatologist diagnosis. Sensitivity of the score was 87.0%, specificity 87.9%, positive predictive value 85.8%, and negative predictive value 89.0%. The Youden index was 0.75. CONCLUSION A score equal to or greater than 7 points correlated well with a rheumatologist diagnosis of flare-up. Our score may constitute a valid objective criterion for standardizing the diagnosis of knee osteoarthritis flare-up, most notably when screening patients for inclusion in therapeutic trials.

Extended report: Randomised, controlled trial of avocado–soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study

Objective To assess the ability of avocado–soybean unsaponifiable—Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Methods Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of ‘progressors’ (JSW loss≥0.5 mm) between groups. Results 399 patients were randomised (345 kept in the FAS), aged 62 (35–84) years, 54% women, mean body mass index 27 (SD 4) kg/m2, mean symptom duration 4 (SD 5) years, 0–100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (−0.638 mm vs −0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. Conclusions 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment. Trial registration number on ClinicalTrial.gov NCT01062737

Randomised, controlled trial of avocado-soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis

Objective To assess the ability of avocado–soybean unsaponifiable—Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Methods Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of ‘progressors’ (JSW loss≥0.5 mm) between groups. Results 399 patients were randomised (345 kept in the FAS), aged 62 (35–84) years, 54% women, mean body mass index 27 (SD 4) kg/m2, mean symptom duration 4 (SD 5) years, 0–100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (−0.638 mm vs −0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. Conclusions 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment. Trial registration number on ClinicalTrial.gov NCT01062737

Erratum: Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee (Clinical Rheumatology DOI: 10.1007/s10067-010-1384- 8)

“Maheu et al. treated 164 patients with osteoarthritis of the knee (114) and hip (50) for 6 months and followed-up for an additional 2 months either ASU 300 or 600 mg (85 patients) or placebo (79 patients).” should read: “Maheu et al. treated 164 patients with osteoarthritis of the knee (114) and hip (50) for 6 months and followed-up for an additional 2 months either ASU 300 mg (85 patients) or placebo (79 patients).”