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Objective: Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects.Methods: In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqMan™ Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip).Results: Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA.Conclusion: The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA. [ABSTRACT FROM AUTHOR]

Objective: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA).Design: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country.Results: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA.Conclusion: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis is a major cause of disability and pain. This phase III, double-blind (patient and observer blinded,) multicenter, randomized, non-inferiority study was conducted to demonstrate the non-inferiority of the highly purified intra-articular injection of hyaluronic acid (Sinovial(®)) in comparison to Hylan G-F20 (Synvisc(®)) in the treatment of knee osteoarthritis.Methods: A total of 381 patients were randomly assigned to receive either the test drug, 16 mg/2 ml (0.8%) highly purified ia hyaluronic acid of biofermentative origin (Sinovial(®)), or the comparative drug, 16 mg/2 ml of 0.8% hylan G-F20 (Synvisc(®)). The duration of the treatment was 2 weeks (three injections at 1-week interval), followed by an observation period of 6 months. The primary efficacy variable was the improvement in mean Western Ontario and McMaster Universities (WOMAC) pain subscore from baseline to the final visit (week 26), compared between the two treatment groups. The acceptable margin for non-inferiority was chosen to be 8 mm.Results: At week 26, WOMAC pain subscores decreased by a mean of 32.5 for both Sinovial(®) and Synvisc(®). These results met prespecified criteria for non-inferiority for both the Intent-to-Treat and Per-Protocol populations. There were no statistically significant differences between groups at 26 weeks, although Sinovial(®)-treated patients tended to have a slightly better outcome for select variables, as they did at earlier time-points, some of which reached statistical significance. Both hyaluronic acid preparations were well-tolerated, with no statistically significant differences in tolerability profile between groups.Conclusion: Sinovial(®) and Synvisc(®) treatments were found to be equivalent, both in terms of efficacy and safety.Clinical Trial Number: NCT00556608 (ClinicalTrials.gov Identifier). [ABSTRACT FROM AUTHOR]

Summary: Objective: Knee osteoarthritis is a major cause of disability and pain. This phase III, double-blind (patient and observer blinded,) multicenter, randomized, non-inferiority study was conducted to demonstrate the non-inferiority of the highly purified intra-articular injection of hyaluronic acid (Sinovial®) in comparison to Hylan G-F20 (Synvisc®) in the treatment of knee osteoarthritis. Methods: A total of 381 patients were randomly assigned to receive either the test drug, 16mg/2ml (0.8%) highly purified ia hyaluronic acid of biofermentative origin (Sinovial®), or the comparative drug, 16mg/2ml of 0.8% hylan G-F20 (Synvisc®). The duration of the treatment was 2weeks (three injections at 1-week interval), followed by an observation period of 6months. The primary efficacy variable was the improvement in mean Western Ontario and McMaster Universities (WOMAC) pain subscore from baseline to the final visit (week 26), compared between the two treatment groups. The acceptable margin for non-inferiority was chosen to be 8mm. Results: At week 26, WOMAC pain subscores decreased by a mean of 32.5 for both Sinovial® and Synvisc®. These results met prespecified criteria for non-inferiority for both the Intent-to-Treat and Per-Protocol populations. There were no statistically significant differences between groups at 26weeks, although Sinovial®-treated patients tended to have a slightly better outcome for select variables, as they did at earlier time-points, some of which reached statistical significance. Both hyaluronic acid preparations were well-tolerated, with no statistically significant differences in tolerability profile between groups. Conclusion: Sinovial® and Synvisc® treatments were found to be equivalent, both in terms of efficacy and safety. Clinical Trial Number: NCT00556608 (ClinicalTrials.gov Identifier). [ABSTRACT FROM AUTHOR]

Summary: Objective: To assess the pain and functional disability levels corresponding to an indication for total joint replacement (TJR) in hip and knee osteoarthritis (OA). Methods: Design: International cross-sectional study in 10 countries. Patients: Consecutive outpatients with definite hip or knee OA attending an orthopaedic outpatient clinic. Gold standard measure for recommendation for TJR: Surgeon’s decision that TJR is justified. Outcome measures: Pain (ICOAP: intermittent and constant osteoarthritis pain, 0–100) and functional impairment (HOOS-PS/KOOS-PS: Hip/Knee injury and Osteoarthritis Outcome Score Physical function Short-form, 0–100). Analyses: Comparison of patients with vs without surgeons’ indication for TJR. Receiver Operating Characteristic (ROC) curve analyses and logistic regression were applied to determine cut points of pain and disability defining recommendation for TJR. Results: In all, 1909 patients were included (1130 knee/779 hip OA). Mean age was 66.4 [standard deviation (SD) 10.9] years, 58.1% were women; 628/1130 (55.6%) knee OA and 574/779 (73.7%) hip OA patients were recommended for TJR. Although patients recommended for TJR (yes vs no) had worse symptom levels [pain, 55.5 (95% confidence interval 54.2, 56.8) vs. 44.9 (43.2, 46.6), and functional impairment, 59.8 (58.7, 60.9) vs. 50.9 (49.3, 52.4), respectively, both P <0.0001], there was substantial overlap in symptom levels between groups, even when adjusting for radiographic joint status. Thus, it was not possible to determine cut points for pain and function defining ‘requirement for TJR’. Conclusion: Although symptom levels were higher in patients recommended for TJR, pain and functional disability alone did not discriminate between those who were and were not considered to need TJR by the orthopaedic surgeon. [ABSTRACT FROM AUTHOR]

Summary: Objective: To compare serum levels of hyaluronic acid (HA) between patients with erosive and non-erosive hand osteoarthritis (HOA), and investigate its association with morphological changes and radiographic progression over 2 years. Methods: Fifty-five women with erosive and 33 women with non-erosive HOA were included in this study. All underwent clinical examination, which included assessment of pain, swelling, deformity and deviation of small hand joints and completed health assessment questionnaires. Serum levels of HA were measured by ELISA. Three-phase bone scintigraphy was performed at baseline. Radiographs of both hands were performed at baseline and after 2 years and scored according Kallman grading scale. Results: Serum levels of HA were significantly higher in patients with erosive than with non-erosive HOA (P <0.01). It correlated significantly with the number of hand joints with deviations and deformities. HA adjusted for age and disease duration significantly correlated with radiographs at baseline and after 2 years in all patients with HOA (r =0.560 and r =0.542, P <0.01 for both correlations). Although there was an association between HA and radiographic score in erosive disease, after adjustment for confounders it remained no longer significant. HA adjusted for confounders correlated significantly with the late phase in all patients with HOA (r =0.412, P <0.01) and in patients with erosive disease (r =0.320, P <0.05). Conclusion: HA is increased in patients with erosive HOA and could be proposed as a surrogate marker with a predictive value for further radiographic progression of HOA in general. Further investigation is necessary to confirm these results. [Copyright &y& Elsevier]

Summary: Aim: To conduct a multi-language translation and cross-cultural adaptation of the Intermittent and Constant OsteoArthritis Pain (ICOAP) questionnaire for hip and knee osteoarthritis (OA). Methods: The questionnaires were translated and cross-culturally adapted in parallel, using a common protocol, into the following languages: Czech, Dutch, French (France), German, Italian, Norwegian, Spanish (Castillan), North and Central American Spanish, Swedish. The process was conducted following five steps: (1) – independent translation into the target language by two or three persons; (2) – consensus meeting to obtain a single preliminary translated version; (3) – backward translation by an independent bilingual native English speaker, blinded to the English original version; (4) – final version produced by a multidisciplinary consensus committee; (5) – pre-testing of the final version with 10–20 target-language-native hip and knee OA patients. Results: The process could be followed and completed in all countries. Only slight differences were identified in the structure of the sentences between the original and the translated versions. A large majority of the patients felt that the questionnaire was easy to understand and complete. Only a few minor criticisms were expressed. Moreover, a majority of patients found the concepts of constant pain and pain that comes and goes to be of a great pertinence and were very happy with the distinction. Conclusion: The ICOAP questionnaire is now available for multi-center international studies. [Copyright &y& Elsevier]

Summary: Objective: To assess the incidence of Total Joint Replacement (TJR) during the long-term follow-up of patients with knee osteoarthritis (OA) formerly receiving treatment with glucosamine sulphate or placebo. Methods: Knee OA patients participating in two previous randomised, placebo-controlled, double-blind, 3-year trials of glucosamine sulphate and receiving treatment for at least 12 months, were systematically contacted to participate in a long-term follow-up retrospective assessment of the incidence of total knee replacement. Results: Out of 340 patients with at least 12 months of treatment, 275 (i.e., 81%) could be retrieved and interviewed for the present evaluation: 131 formerly on placebo and 144 on glucosamine sulphate. There were no differences in baseline disease characteristics between groups or with the patients lost to follow-up. The mean duration of follow-up was approximately 5 years after trial termination and treatment discontinuation, making up a total of 2178 patient-years of observation (including treatment and follow-up). Total knee replacement had occurred in over twice as many patients from the placebo group, 19/131 (14.5%), than in those formerly receiving glucosamine sulphate, 9/144 (6.3%) (P =0.024, chi-square test), with a Relative Risk that was therefore 0.43 (95% confidence interval (CI): 0.20–0.92), i.e., a 57% decrease compared with placebo. The Kaplan Meier/Log–Rank test survival analysis confirmed a significantly decreased (P =0.026) cumulative incidence of total knee replacements in patients who had received glucosamine sulphate. A pharmacoeconomic analysis in a subgroup of subjects suggested that patients formerly on glucosamine sulphate had recurred to less symptomatic medications and use of other health resources than those from the placebo group during the last year of follow-up. Conclusions: Treatment of knee OA with glucosamine sulphate for at least 12 months and up to 3 years may prevent TJR in an average follow-up of 5 years after drug discontinuation. [Copyright &y& Elsevier]

Summary: Objective: Knee pain relief has been suggested to potentially alter radioanatomic positioning in conventional standing antero-posterior knee radiographs. This study was performed to determine whether this is always the case and in particular if it applied to two recent randomised, placebo-controlled trials showing both symptom- and structure-modification with glucosamine sulfate in knee osteoarthritis. Design: Patients in the two studies were selected if they completed the 3-year evaluations and, irrespectively of treatment, (1) were pain-improvers in that they underwent Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (WOMAC) pain decrease at least equal to the mean improvement observed with glucosamine sulfate, or (2) if their baseline standing knee pain (item #5 of the WOMAC pain scale) was “severe” or “extreme” and improved by any degree at the end of the trials. Changes in minimum joint space width were then compared between treatments. Results: Knee pain was of mild-to-moderate severity in the two original studies and in all patient subsets identified here. Obviously, there were more pain-improvers in the glucosamine sulfate than in the placebo subsets (N =76 vs 57 in pooling the two studies), but WOMAC pain scores improved to the same extent (over 50% relative to baseline). Notwithstanding such a major pain relief, patients in the placebo subsets of both studies suffered a definite mean (SE) joint space narrowing, that was of −0.22 (0.15)mm in the pooled analysis, and that was not observed with glucosamine sulfate: +0.15 (0.07)mm; P =0.003. Similar evidence was found in the smaller subsets with at least severe baseline standing knee pain improving after 3 years. Conclusions: Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials, possibly due to the mild-to-moderate patient characteristics. Consensus deliverables should acknowledge that the potential limitations of conventional standing antero-posterior radiographs should not be overestimated since they may not apply to all patient populations and to all studies using this gold standard technique. [Copyright &y& Elsevier]

OBJECTIVE: To evaluate the frequency of upper gastrointestinal (GI) tract adverse events associated with risedronate during two (2-year) randomized, double-blind, parallel-group, placebo-controlled studies. PATIENTS AND METHODS: Male and female patients aged 40 to 80 years with mild to moderate medial-compartment knee osteoarthritis were enrolled. Data were pooled and analyzed for risedronate at 5 mg and at 15 mg once daily and compared with placebo. The results of the once-weekly dosages (35 or 50 mg) were assessed separately. RESULTS: A total of 2483 patients were randomized: 622 to placebo, 628 to risedronate at 5 mg/d, 609 to risedronate at 15 mg/d, 310 to risedronate at 35 mg once weekly, and 314 to risedronate at 50 mg once weekly. During the study, 77% of patients were regular nonsteroidal anti-inflammatory drug (NSAID) and/or analgesic users (defined as those who took medication 23 days per week), and 68% were regular NSAID users. The number of upper GI tract adverse events was similar between treatment groups, with no dose-related response: 161 for placebo, 176 for rlsedronate at 5 mg/d, and 150 for risedronate at 15 mg/d. The time to the first upper GI tract adverse event was similar between treatment groups. There was no difference in the frequency of upper GI tract adverse events In risedronate-treated patients compared with patients who were regular users of NSAIDs or NSAIDs and/or analgesics. Findings were similar for those in the once-weekly risedronate groups. CONCLUSION: The results of this study show that risedronate regimens at 5 mg/d or 15 mg/d as well as once weekly at 35 mg or 50 mg are not associated with an increased frequency of upper GI tract adverse events, even in patients who have an increased risk for such events. [ABSTRACT FROM AUTHOR]

Les AINS sont efficaces pour réduire les douleurs et les raideurs articulaires chez les patients (pts) atteints de SpAax [1]. Toutefois, l'utilisation prolongée des AINS peut entraîner une toxicité gastro-intestinale, cardiovasculaire et rénale [2]. Notre objectif a été d'évaluer l'effet à long terme du sécukinumab (SEC) sur la consommation d'AINS chez les pts ayant une SpAax-r active à partir des données combinées de 3 études de phase 3 (MEASURE 2-4). La prise d'AINS a été évaluée en prospectif via le score ASAS-AINS [3]. Ce score prend en compte le type d'AINS, la dose quotidienne et le nombre de jour de prise sur la période d'intérêt. Un score ASAS-AINS de « 0 » indique l'absence de prise d'AINS. Seuls les pts traités par SEC 150 ou 300 mg et ayant un score ASAS-AINS > 0 à l'inclusion ont été analysés. Les pts traités par placebo jusqu'à S24 puis re-randomisés dans les bras SEC 150 ou 300 mg ont été inclus dans leurs groupes de dose SEC respectifs. La variation moyenne du score ASAS-AINS par rapport à l'inclusion, la proportion de pts ayant soit une réduction de 50 % du score ASAS-AINS soit un score ASAS-AINS < 10 ont été calculés pour chaque dose à 2, 3 et 4 ans. Suivant la distribution du score ASAS-AINS à l'inclusion, deux sous-groupes ont été évalués: – < 75 (faibles consommateurs); – ≥ 75 (forts consommateurs). Au total, 562 pts (SEC 150 mg n = 467; 300 mg n = 95) ont été inclus dans l'analyse. Le score moyen ASAS-AINS a diminué avec le temps dans les deux groupes (ΔASAS-AINS SEC 150 mg/300 mg: −13,5/ − 11,3 à 2 ans; −17,4/ − 12,0 à 3 ans; −19,0/NA à 4 ans). Une réduction plus importante a été observée chez les pts forts consommateurs d'AINS. La proportion de pts avec une réduction de 50 % du score ASAS-AINS ou atteint un score ASAS-AINS < 10 a augmenté avec le temps dans les deux groupes (Tableau 1). Sous SEC, le score ASAS-AINS a été durablement amélioré et une épargne en AINS cliniquement significative a été observée au long cours chez les pts atteints de SA, qu'ils soient faibles ou forts consommateurs d'AINS. [ABSTRACT FROM AUTHOR]