Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.     

Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen

OBJECTIVE: Non-steroidal antiinflammatory agents are commonly used to treat pain and inflammation associated with osteoarthritis (OA), but have poor gastrointestinal (GI) tolerability. This study compared the efficacy of the COX-2 specific inhibitor valdecoxib with naproxen and placebo, in treating symptomatic OA of the hip. DESIGN: This multicenter, randomized, double-blind 12-week study compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg and 10 mg with placebo or naproxen 500 mg BID. Efficacy was assessed by Patient's and Physician's Global Assessment of Arthritis, and the WOMAC (Western Ontario and McMasters) OA Individual and Composite Indices. The incidence of adverse events was monitored throughout the study. RESULTS: Valdecoxib was clinically and statistically superior to placebo for Patient's and Physician's Global Assessment of Arthritis and for all WOMAC OA Indices over the 12 week study period (P相似文献   

Aceclofenac vs paracetamol in the management of symptomatic osteoarthritis of the knee: a double-blind 6-week randomized controlled trial

OBJECTIVE: To evaluate the efficacy and tolerability of aceclofenac, 200 mg/day, and paracetamol, 3000 mg/day, in the treatment of osteoarthritis (OA) of the knee. METHODS: This was a double-blind, parallel-group, multicentre clinical trial involving patients with symptomatic OA of the knee, conducted in Spain. Patients were randomly allocated to aceclofenac 100 mg twice daily (n=82) or paracetamol 1000 mg three times daily (n=86). Patients were assessed at baseline and 6 weeks. Primary efficacy measures were severity of pain (visual analogue scale, VAS), Lequesne OA knee index, and patient's and physician's global assessment of disease activity. Severity of knee pain at rest or walking, stiffness, knee swelling and tenderness, and assessment of health-related quality of life (Health Assessment Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form 36) were included as secondary endpoints. RESULTS: Both treatment groups showed significant improvement compared with their baseline values in the four primary endpoints. Mean between-treatment differences favoured aceclofenac over paracetamol on pain (VAS, 7.64 mm [95% confidence interval (CI), 0.44-14.85 mm]), Lequesne OA index (1.41 [95% CI, 0.45-2.36]), and patient's (0.33 [95% CI, 0.06-0.61]) and physician's (0.23 [95% CI, 0.01-0.47]) global assessments. Adverse events were similar for both drugs (paracetamol, 29% patients vs aceclofenac, 32%; P=0.71). Four patients withdrew in each group due to adverse events. Patients tended to prefer aceclofenac to paracetamol (P=0.001), and more treated with paracetamol withdrew from the study due to lack of efficacy (n=8 vs n=1, P=0.035, for paracetamol and aceclofenac, respectively). CONCLUSION: At 6 weeks, patients with symptomatic OA of the knee showed a greater improvement in pain and functional capacity with aceclofenac than paracetamol with no difference in tolerability.     

Efficacy and safety of a single intra-articular injection of non-animal stabilized hyaluronic acid (NASHA) in patients with osteoarthritis of the knee

OBJECTIVE: Non-animal stabilized hyaluronic acid (NASHA) is a novel hyaluronan (HA) preparation with a 4-week intra-articular half-life. This study compared the efficacy of a single injection of NASHA with placebo in patients with osteoarthritis (OA) of the knee. DESIGN: This was a 26-week randomized, double-blind, multicenter study of a single intra-articular knee injection with either NASHA or placebo (saline). Assessments included the Western Ontario McMasters Universities osteoarthritis index (WOMAC, Likert Scale) and patients' overall global disease status. A positive response was defined as a reduction in WOMAC pain score for the study knee of 40% from baseline with a minimum improvement of > or =5 points. RESULTS: A total of 346 (NASHA 172; placebo 174) patients were treated. WOMAC scores and quality of life were improved in both the NASHA and placebo groups. For the overall population, there were no statistically significant between-group differences in response rates for any efficacy parameters. In patients with OA confined to the knee (N=216), a greater response to NASHA than placebo was observed at week 6 (P=0.025). There were few treatment-related events. CONCLUSIONS: NASHA was not superior to placebo for the primary efficacy analysis. However, these data may be confounded by the inclusion of patients with OA at other sites, as significant benefits over placebo were found among patients with OA confined to the knee. Future trials of OA that examine a local therapy might need to consider restricting the study population to those patients having OA of only the signal joint.     

Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study

In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days. IMPLICATIONS: In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo.     

A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon) as a structure modifying therapy in osteoarthritis of the hip and knee

OBJECTIVE: To determine the structure (disease) modifying effect of a glycosaminoglycan polypeptide association complex (GP-C; Rumalon) in patients with knee and hip osteoarthritis (OA). METHODS: Double-blind, randomized, placebo-controlled five-year study. Primary assessment criterion was change in radiographic joint space width between baseline and follow-up at 5 years. Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs). The patients received 10 courses of injections of placebo or GP-C 2 ml intramuscularly in 5 years (two courses each year). Each course included 15 injections administered twice weekly. RESULTS: There were 277 patients with knee OA and 117 patients with hip OA. Control and GP-C treated groups were comparable as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at the baseline. Knee joint space at 5 years decreased 0.37+/-0.08 (mean+/-standard deviation) mm for GP-C and 0.42+/-0.08 mm for placebo groups (P=0.68). Hip joint space at 5 years decreased 0.21+/-0.08 mm for GP-C and 0.22+/-0.08 mm for placebo groups (P=0.53). In a subset of patients with hip OA, Kellgren-Lawrence> or =2 and JSW> or =1 mm, there was a trend in favor of GPC for lower joint space narrowing in 5 years (P=0.11). In addition, there were no statistical differences between the treatment groups in LAI, pain on passive motion and consumption of NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent than in the placebo group (15%). CONCLUSION: We were not able to demonstrate a structure modifying effect of GP-C in OA of the hip or knee. Radiographic progression of OA in both knee and hip OA was lower than expected in both study groups.     

Efficacy of duloxetine by prior NSAID use in the treatment of chronic osteoarthritis knee pain: A post hoc subgroup analysis of a randomized,placebo-controlled,phase 3 study in Japan

Background

A previously conducted placebo-controlled, randomized, phase 3 study of 353 Japanese patients with knee osteoarthritis (OA) showed significant improvements for duloxetine vs placebo in pain and health-related quality of life (HRQoL) (ClinicalTrials.gov Identifier: NCT02248480). Reported here are post hoc subgroup analyses evaluating the efficacy of duloxetine according to the pattern of prior nonsteroidal anti-inflammatory drug (NSAID) use.

Superior responsiveness of the pain and function sections of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as compared to the Lequesne-Algofunctional Index in patients with osteoarthritis of the lower extremities

OBJECTIVE: To compare the responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a questionnaire format of the Lequesne-Algofunctional Index in patients with OA of the lower extremities. METHODS: Longitudinal analysis of the instruments' responsiveness [standardized response mean (SRM), effect size (ES)] in ambulatory patients undergoing hip or knee arthroplasty. RESULTS: At six months 36, and at one year 40 out of 43 patients undergoing hip (N=30) or knee arthroplasty (N=13) could be examined. Both responsiveness statistics revealed the same order of responsiveness. For both indices and for both locations, the pain sections were more responsive than the function sections. However, the WOMAC scales and the WOMAC global index (hip at 12 months: SRM=2.4; knee at 12 months: SRM=2.0 ) were more responsive than the comparable Lequesne sections and Lequesne index (hip at 12 months: SRM=2.1; knee at 12 months: SRM=1.5). CONCLUSIONS: Although our results are based on a German version using a self-report format, the WOMAC scales appear to be more responsive than the Lequesne index in patients with OA of the lower extremities.     

Changes in pain, stiffness and physical function in patients with osteoarthritis waiting for hip or knee joint replacement surgery

OBJECTIVE: Little has been reported on changes in health status in patients with osteoarthritis (OA) while waiting for hip or knee replacement surgery. In this study we assessed (1) changes in self-reported pain, stiffness and physical function in patients with OA of the hip or knee, from the decision to undergo surgery to 14 days prior to surgery, and (2) the determinants of these changes. METHODS: Among 353 baseline respondents, 170 waited >30 days for surgery, completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) before surgery and were included in the analysis of changes; 120 with OA of the hip and 50 of the knee. We analyzed changes in WOMAC scores using the paired t test and determinants of the changes using multiple linear regression. RESULTS: Patients with OA of the hip did not change on any WOMAC scale before surgery. Knee patients deteriorated with time on the WOMAC stiffness and total scales, but not on the pain or physical function subscales. In both patient categories, higher baseline WOMAC scores were associated with smaller changes on all subscales and the total score, and female sex was associated with deterioration on the pain subscale. CONCLUSIONS: Patients with OA of the hip reported no change in pain, stiffness or physical function while waiting for joint replacement surgery, whereas patients with OA of the knee deteriorated on the stiffness and total scales of the WOMAC. This suggests a difference in patient selection, referral pattern or disease development between the patient categories.     

Relationship of limb length inequality with radiographic knee and hip osteoarthritis

OBJECTIVE: This study examined the relationship of limb length inequality (LLI) with radiographic hip and knee osteoarthritis (OA) in a large, community-based sample. METHODS: The total study group comprised 926 participants with radiographic knee OA, 796 with radiographic hip OA, and 210 (6.6%) with LLI >or=2cm. The presence of radiographic OA was defined as Kellgren/Lawrence (K/L) grade >or=2. Multiple logistic regression models were used to examine the relationship of LLI with hip and knee OA, while controlling for age, gender, race, body mass index, and history of hip or knee problems (joint injury, fracture, surgery, or congenital anomalies). RESULTS: In unadjusted analyses, participants with LLI were more likely than those without LLI to have radiographic knee OA (45.1% vs 28.3%, P<0.001) and radiographic hip OA (35.2% vs 28.7%, P=0.063). In multiple logistic regression models, knee OA was significantly associated with presence of LLI (adjusted Odds Ratio [aOR]=1.80, 95% Confidence Interval [95% CI] 1.29-2.52), but there was no significant relationship between hip OA and LLI (aOR=1.20, 95% CI 0.86-1.67). Among participants with LLI, right hip OA was more common when the contralateral limb was longer than when the ipsilateral limb was longer (30.3% vs 17.5%, P=0.070). CONCLUSION: LLI was associated with radiographic knee OA, controlling for other important variables. Future research should examine the relationship of LLI with hip or knee OA incidence, progression, and symptom severity, as well as the efficacy for LLI corrective treatments in OA.     

A comparison of outcomes in osteoarthritis patients undergoing total hip and knee replacement surgery

OBJECTIVE: The aims of this study were to assess changes in physical function and quality of life with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the instrument of the Medical Outcomes Study SF-36 Health Survey (MOS SF-36), respectively, in patients undergoing hip anf knee joint replacement surgery and to compare the responsiveness of these two outcome measures 1 year after surgery. DESIGN: One hundred and ninety-four patients with osteoarthritis (OA knee 108, OA hip 86) admitted to four hospitals in Sydney were followed over a period of 1 year at 3 monthly intervals. RESULTS: WOMAC measures improved significantly after 1 year for OA hip and OA knee: there was reduction in pain of 71% and 53%, reduction of stiffness of 55% and 43% and improvement in physical function of 68% and 43%, respectively. MOS SF-36 measures in those having hip surgery improved significantly for pain (222%), physical function (247%), physical role functioning (402%), general health (110%), vitality (143%0, social functioning (169%) and mental health (114%). For those in the knee surgery group, significant improvement was seen for pain (175%), physical function (197%), physical role functioning (275%), vitality (125%) and social functioning (119%). The WOMAC was a more responsive measure than the MOS SF-36. CONCLUSION: WOMAC and MOS SF-36 detect significant and clinically meaningful changes in outcome after hip and knee replacement. WOMAC requires a smaller sample size and is more responsive in the short term. For a follow-up longer than 6 months MOS SF-36 provides additional information. The improvement in outcomes following hip joint surgery were significantly greater than those following knee surgery.     

Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study

OBJECTIVE: This preliminary study sought to determine whether using 1500/1200mg of glucosamine hydrochloride and chondroitin sulfate (GH/CS) is effective, both separately and combined with exercise, compared to a placebo plus exercise program in improving physical function, pain, strength, balance, and mobility in older adults with knee osteoarthritis (OA). METHODS: This double-blind, placebo-controlled, randomized clinical trial lasted 12 months. Participants included 89 older adults (age>/=50 years) with knee OA randomized to either GH/CS or placebo group. Phase I was a 6-month trial comparing the effects of assignment to either GH/CS or placebo. Phase II added 6 months of exercise for both groups. The primary outcome measure was Western Ontario and McMaster University Osteoarthritis Index (WOMAC) function, and secondary outcome measures included WOMAC pain, 6-min walk, balance, and knee strength. RESULTS: Of the 89 randomized participants, 72 (81%) completed the study. The median pill compliance was 94% and 95% in Phase I, and, in Phase II, 97% and 91% for the GH/CS and placebo groups, respectively. Median exercise compliance during Phase II was 77% for the GH/CS group and 78% for the placebo group. WOMAC function and pain did not differ significantly between the groups at 6- or 12-month follow-up. There were also no significant differences between the groups in 6-min walk or knee strength; however, balance was better in the placebo group with approximately a 10% difference compared to the GH/CS group. CONCLUSIONS: The GH/CS group was not superior to the placebo group in function, pain, or mobility after both phases of the intervention (pill only and pill plus exercise).     

Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee

OBJECTIVE: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index is a tested questionnaire to assess symptoms and physical functional disability in patients with OA of the knee and the hip. We adapted the WOMAC for the Italian language and tested its metric properties in 304 patients with symptomatic OA of the knee. METHODS: Three hundred and four consecutive patients, attending 29 rheumatologic outpatient clinic in northern, central, and southern Italy, were asked to answer two disease-specific questionnaires (WOMAC and Lequesne algofunctional index) and one generic instrument (Medical Outcomes Study SF-36 Health Survey-MOS SF-36). A sample of 258 patients was readministered the WOMAC 7-10 days after the first visit and the structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using intraclass correlation coefficients (ICCs), and construct and discriminant validity using Spearman's correlations, Wilcoxon rank sum test, and Kruskal-Wallis test. RESULTS: All WOMAC subscales (pain, stiffness, and physical function) were internally consistent with Cronbach's coefficient alpha of 0.91, 0.81, and 0.84, respectively. Test-retest reliability was satisfactory with ICCs of 0.86, 0.68, and 0.89, respectively. In comparison with the SF-36, the expected correlations were found when comparing items measuring similar constructs, supporting the concepts of convergent construct validity. Very high correlations were also obtained between WOMAC scores and Lequesne OA algofunctional index. WOMAC physical function, but not WOMAC stiffness and pain subscales, was weakly associated with radiological OA severity (P=0.03). Also, WOMAC pain score was inversely correlated (P=0.01) with years of formal education. Examination of discriminant validity showed that the scores on the WOMAC and SF-36 followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. CONCLUSION: The Italian version of WOMAC is a reliable and valid instrument for evaluating the severity of OA of the knee, with metric properties in agreement with the original, widely used version.     

Clinical effectiveness and safety of intra-articular injection of HYALGO in the management of knee osteoarthritis symptoms: A multicenter prospective study

BackgroundThe reduced concentration of hyaluronic acid in the synovial fluid, leading to impairment of joint function and painful symptomatology during knee osteoarthritis (OA), can be restored by using injectable formulations of hyaluronic acid (HA) and chondroitin sulfate (CS), variable for relative composition, HA/CS molecular modifications, and injection protocols. The present study aims to assess the safety and performance of the intra-articular (IA) viscosupplementing agent HYALGO, a formulation combining 40 mg/mL HA (>1700 kDa) and 40 mg/mL CS, in the treatment of patients suffering from knee OA.Methods74 patients affected by knee lesions classified as grade II and III according to Kellgren and Lawrence classification were prospectively recruited and treated with three HYALGO injections (2 mL) given one week apart. Visual analogue scale (VAS) pain changes were monitored at each injection and over-time at 6, 14, and 26 weeks of follow-up. Secondary endpoints were: Western Ontario McMaster University Osteoarthritis index (WOMAC), Patient's Global Assessment (PGA) score, Clinical Observer Global Assessment (COGA) score, Outcome Measures in Rheumatology Committee (OMERACT) and Osteoarthritis Research Society International (OARSI) responders rates. Patients were also assessed for changes in their ultrasound joint scores according to the criteria of the OMERACT US Task Force Group.ResultsPain reduction was statistically significant starting from the first IA injection. Mean pain reduction from baseline to week 26 was −90.6%. At 26 weeks, WOMAC Pain was reduced by −62.7%, WOMAC Stiffness by −47.2%, WOMAC Physical Function by −54.1%; Total WOMAC by −53.8%. The VAS PGA change from baseline was −48.0 [mm] and VAS COGA -41.0 [mm]. Responders at week 26 were 78.4%. Ultrasound parameters (joint effusion, synovial thickness, and popliteal cysts) improved or remained stable from baseline to week 6.ConclusionsThree injections of HYALGO were safe and effective to manage symptomatic knee OA, with a beneficial effect that increased progressively over time, peaking 6 months after injection.     

Relief in mild-to-moderate pain is not a confounder in joint space narrowing assessment of full extension knee radiographs in recent osteoarthritis structure-modifying drug trials

OBJECTIVE: To assess whether improvement in knee pain biased the determination of the structure-modifying effect reported for glucosamine sulfate in two recent 3-year, randomised, placebo-controlled clinical trials, in which conventional standing antero-posterior full extension knee radiographs were used for the measurement of joint space narrowing, and in which pain relief might have improved knee full extension. DESIGN: Patients completing the 3-year treatment course were selected based on a WOMAC pain decrease at least equal to the mean improvement in the glucosamine sulfate arms in either of the original studies, irrespective of treatment with glucosamine sulfate or placebo (drug responders or placebo responders). In a second approach, 3-year completers were selected 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. In both cases, changes in minimum joint space width were compared between treatment groups. RESULTS: Global knee pain was mild-to-moderate in the two study populations and in all patient subsets identified. There were obviously more pain improvers in the glucosamine sulfate subsets (N=76 in the two studies combined) than in the placebo subsets (N=57), but WOMAC pain scores improved to the same extent, which was as large as over 50% relative to baseline. Nevertheless, the placebo subsets in both studies underwent an evident mean (SD) joint space narrowing, which in the pooled analysis of both studies was -0.22 (0.80) mm, and was not observed with glucosamine sulfate: +0.15 (0.60) mm (P=0.003 vs placebo). Similar results were found in the smaller subsets with > or = severe baseline standing knee pain that improved after 3 years, with a joint space narrowing nevertheless of -0.28 (0.76) mm with placebo (N=26), not observed with glucosamine sulfate: +0.21 (0.68) mm (N=31; P=0.014 vs placebo). CONCLUSIONS: Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials using conventional standing antero-posterior radiographs, possibly due to the mild-to-moderate patient characteristics.     

Validation of the Western Ontario and Mcmaster University osteoarthritis index in Asians with osteoarthritis in Singapore

OBJECTIVE: To assess the reliability and validity of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) as an outcome measure in Asian patients with knee or hip osteoarthritis (OA) in Singapore. DESIGN: The WOMAC was administered twice 7 days apart to 66 consecutive English-speaking Chinese, Malay or Indian inpatients and outpatients with knee or hip OA seen at a tertiary referral centre through a structured interview, which also assessed demographic and other characteristics. Internal consistency was assessed using Cronbach's alpha, reliability using Spearman's correlations, intraclass correlations and repeatability coefficients, and relationships between WOMAC domains and known determinants of function using Spearman's correlations and the Mann-Whitney U-test. RESULTS: The WOMAC showed good internal consistency (alpha=0.70 to 0.93) and good reliability, with intraclass correlations of 0.83 to 0.90 and mean test-retest score differences of 0.02 to 0.13 points (possible range 4 points). Results of Likert scoring assessment supported the validity of the WOMAC when interpreted in the context of the close association between pain and physical function. Eight of nine a priori hypotheses relating WOMAC Pain and Physical Function scores to known determinants of function were present, supporting construct validity of this scale. CONCLUSION: The WOMAC is a valid and reliable outcome measure in Asian patients with OA in Singapore.     

A randomized controlled trial to evaluate the slow-acting symptom modifying effects of a regimen containing colchicine in a subset of patients with osteoarthritis of the knee

OBJECTIVE: As crystals may contribute to inflammation in osteoarthritis (OA), it is hypothesized that colchicine may have symptom/disease modifying effects in OA. The objective of this study was to evaluate the symptomatic benefit of addition of colchicine to a regimen of intraarticular steroids and piroxicam in patients with knee OA with inflammation. DESIGN: 39 patients with OA of the knee with persisting inflammation, despite at least 2 weeks of piroxicam, were subjected to intraarticular steroid injection and randomly assigned to receive colchicine 0.5 mg twice daily or placebo in a randomized, double blind, placebo-controlled trial over 5 months. RESULTS: VAS for index knee pain (VAS-pain) and total KGMC score (a modified WOMAC index) at 16 and 20 weeks were significantly better in the colchicine group than the corresponding scores in controls. The benefit persisted on multivariate analysis at 16 weeks (Hotellings T(2)=18.6, F(5,33)=3.3154, P=0.015). The proportion of patients who had 30% or greater response at 16 weeks was significantly higher in the colchicine group in VAS-pain (69% vs 15%) and total KGMC scores (74% vs 45%) and the significance persisted on combined analysis using Mantel-Haenszel test (M-H Risk=5.9, 95% C.I.: 2.08 to 16.73). At 20 weeks, benefit of colchicine therapy was seen on pooled analysis only (M-H risk=3.71, 95% C.I.: 1.07=8.02). CONCLUSION: The addition of colchicine produced significantly greater symptomatic benefit at 16 and 20 weeks than intraarticular steroid and piroxicam alone in patients with knee OA with inflammation.     

Clinical evaluation of the WOMAC 3.0 OA Index in numeric rating scale format using a computerized touch screen version

BACKGROUND: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index is a previously described self-administered questionnaire covering three domains: pain, stiffness and function. It has been validated in patients with osteoarthritis (OA) of the hip or knee in a paper-based format. AIM: To validate the WOMAC 3.0 using a numerical rating scale in a computerized touch screen format allowing immediate evaluation of the questionnaire. In the computed version cartoons, written and audio instruments were included in order facilitate application. METHODS: Fifty patients, demographically balanced, with radiographically proven primary hip or knee OA completed the classical paper and the new computerized WOMAC version. Subjects were randomized either to paper format or computerized format first to balance possible order effects. RESULTS: The intra-class correlation coefficients for pain, stiffness and function values were 0.915, 0.745 and 0.940, respectively. The Spearman correlation coefficients for pain, stiffness and function were 0.88, 0.77 and 0.87, respectively. CONCLUSION: These data indicate that the computerized WOMAC OA index 3.0 is comparable to the paper WOMAC in all three dimensions. The computerized version would allow physicians to get an immediate result and if present a direct comparison with a previous exam.     

Behandlung der Gonarthrose

OBJECTIVE: The aim of this trial was to compare acemetacin (ACE) with celecoxib (CEL) in terms of tolerability and efficacy in the treatment of osteoarthritis of the knee joint. METHODS: A total of 105 patients (26-64 years old) suffering from primary osteoarthritis (OA) of the knee were enrolled in this international, multicenter, randomized, double blind controlled trial. Fifty three patients were given ACE and 52 CEL. They were treated with either 90 mg bid of slow release ACE or 200 mg bid of CEL for 6 weeks. Additional gastroprotective therapy was not provided. Tolerability was assessed by physical examination, laboratory tests, vital signs and reports of side effects, as well as by patient and physician global assessments. Efficacy parameters comprised pain assessment by visual analogue scale (VAS) and ordinal scale, WOMAC, SF-36 and patient and physician global impressions of efficacy. In addition, acetaminophen consumption was recorded. RESULTS: In 21 ACE (39.6%) and 19 CEL patients (36.5%), the number of side effects totaled 56 (ACE n=29; CEL n=27) (ns). Mean pain reduction at week 6 was highly significant ( P<0.0001) in both groups and amounted to 38.7 mm (+/-20.3) in the ACE group and to 35.1 mm (+/-18.7) in the CEL group (ns). Very similar results were seen with respect to the other efficacy parameters. CONCLUSION: ACE is not inferior to CEL for the short-term treatment of knee OA in terms of tolerability and efficacy.     

Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee

Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. The study included 200 hospitalized patients with active OA of the knee, symptoms for at least 3 months and a Lequesne's index of at least 7 points. Patients were evaluated weekly. Response was defined as a reduction in the Lequesne's index by at least 2 points if the enrollment value was higher than 12 points, or by at least 1 point if the enrollment value was 12 or less points, together with a positive overall assessment by the investigator. The improvement tended to be sooner under ibuprofen (48% responders vs 28% after the 1st treatment week; P = 0.06, Fisher's Exact test), but there was no difference from the 2nd week onward, with a success rate of 52% in the ibuprofen group and of 48% in the glucosamine group (P = 0.67) at the end of treatment. The average Lequesne's index at enrollment was around 16 points and decreased by over 6 points in both groups, again with the above described trend. On the other hand, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine (P < 0.001, Fisher's Exact test). The number of adverse event related drop-outs was different between the two groups (7% vs 1%, respectively; P = 0.035). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.