Efficacy and safety of topical nimesulide in the treatment of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs. Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues. OBJECTIVES: In this double-blind, randomized, placebo-controlled study design, we aimed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients. METHODS: Seventy-four adult knee OA outpatients were enrolled. We used Western Ontario and McMaster Universities OA Index (WOMAC), Nottingham Health Profile (NHP), and patient and physician global satisfaction scores. WOMAC and NHP scores were measured at the initial and final visit. Treatment group received topical nimesulide gel 1% on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days. RESULTS: There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values. The overall WOMAC scores was significantly better than placebo (P = 0.03), but physical functioning, stiffness, and pain scales did not reach statistical significance. For the NHP scores there was an improvement at "energy level," "pain," "physical motion," and "NHP distress" scores in the treatment group whereas no improvement was found in the placebo group. Between-group differences were not significant. Both patient and physician satisfaction scores were significantly better in the treatment group. CONCLUSION: This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA.     

A randomized controlled trial comparing topical piroxicam gel with a homeopathic gel in osteoarthritis of the knee

OBJECTIVE.: To evaluate the efficacy and safety of a homeopathic gel vs an NSAID (piroxicam) gel in the treatment of osteoarthritis of the knee. METHOD.: One hundred and eighty-four out-patients with radiographically confirmed symptomatic osteoarthritis of the knee were entered into a pragmatic, randomized, double-blind controlled trial and treated with 1 g of gel three times daily for 4 weeks. Main outcome measures were pain on walking as a Visual Analogue Score (VAS) and a single-joint Ritchie index. RESULTS.: One hundred and seventy-two of the 184 enrolled patients had endpoints for the main outcome parameters. The pain reduction was 16.5 mm VAS in the homeopathy group (n = 86) and 8.1 mm in the piroxicam group (n = 86); the difference between treatment groups was 8.4 mm (95% confidence interval 0.8-15.9), and after adjustment for pain at baseline it was 6.8 mm (95% confidence interval -0.3 to 13.8). There was no significant difference between treatment groups in the single-joint Ritchie index (P = 0.78). Adverse events occurred in 28 patients (12 homeopathy group, 5 withdrawn; 16 piroxicam group, 9 withdrawn); 18 of the events involved a local reaction (7 homeopathy group, 2 withdrawn; 11 piroxicam group, 5 withdrawn). CONCLUSION.: The homeopathic gel was at least as effective and as well tolerated as the NSAID gel. The presence of a clinically relevant difference between treatment groups cannot be excluded. The homeopathic gel supplemented by simple analgesics if required may provide a useful treatment option for patients with osteoarthritis.     

Celecoxib versus diclofenac in the management of osteoarthritis of the knee

OBJECTIVE: A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care. METHODS: Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial. RESULTS: Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib. CONCLUSION: Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.     

Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee

Aim: To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. Methods: This is a prospective, double‐blind, placebo‐controlled and intention‐to‐treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. Results: Of 84 patients screened, 74 patients formed the intent‐to‐treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry‐over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05). Conclusion: Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.     

Efficacy of EMG-biofeedback in knee osteoarthritis

This study was designed to investigate the additive effect of EMG-biofeedback in rehabilitation of knee osteoarthritis. Forty patients, aged 45–70, with the diagnosis of knee osteoarthritis according to American College of Rheumatology (ACR) criteria were taken into the study. The patients were randomly assigned in two groups. One group (n = 20) received strengthening exercise program with EMG-biofeedback while the other group (n = 20) had the same exercise program without biofeedback for 3 weeks. The clinical outcome was assessed on the basis of pain with visual analog scale (VAS), function with Western Ontario McMaster Osteoarthritis Index (WOMAC) and quality of life with Nottingham Health Profile (NHP). Quadriceps strength was measured with Cybex isokinetic dynamometer, isokinetically at the angular velocities of 60 and 180°/s and isometric strength at 65° of knee flexion. Pain, WOMAC scores and muscle strength improved in both groups but there was no statistically significant differences between two groups (p > 0.05). In both groups physical mobility, pain scores of NHP improved significantly (p < 0.001) while in EMG-biofeedback group energy and sleep scores also improved after treatment (p < 0.05). As reported in the literature, in our study, strengthening exercises improved pain, function, muscle strength and quality of life in patients with knee osteoarthritis. But it seems that there is no significant additive effect of EMG-biofeedback to regular strengthening exercise program in these patients.     

Equivalence study of a topical diclofenac solution (pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial

OBJECTIVE:. To compare the safety and efficacy of a topical diclofenac solution versus oral diclofenac in relieving the symptoms of primary osteoarthritis (OA) of the knee, in a randomized, double-blind, double-dummy equivalence trial. METHODS: A total of 622 men and women with radiological evidence of primary knee OA and mild to severe symptoms were randomly assigned to treatment with a topical diclofenac solution plus placebo oral capsules, or placebo topical solution plus oral diclofenac (50 mg) capsules. Patients applied 50 drops of study solution and took 1 study capsule 3 times daily for 12 weeks. Efficacy variables were pain and physical function, measured by the Western Ontario and McMaster Universities (WOMAC) VA 3.1 OA Index, and patient global assessment (PGA). Equivalence in the per-protocol group was based on previously defined ranges of clinically significant difference. Safety was assessed by evaluation of adverse events, vital signs, and laboratory data. RESULTS: The difference in mean (95% CI) change scores (final minus baseline) between treatments was 13.3 mm (-8.6 to 35.2) for pain (total scale 500 mm), 71.0 mm (-2.4 to 144.5) for physical function (total scale 1700 mm), and 4.3 mm (-1.2 to 9.8) for PGA (total scale 100 mm). The CI for each efficacy variable fell within the predefined equivalence ranges (pain, +/- 75 mm; physical function, +/- 255 mm; PGA, +/- 20 mm), indicating that no clinically relevant difference was found between the 2 treatment arms. Safety analyses of patients applying topical diclofenac solution revealed some minor skin irritation at the application site--mostly skin dryness in 83/311 (27%) patients--but a significantly reduced incidence, relative to oral diclofenac, of total and severe gastrointestinal (GI) adverse events, including dyspepsia, abdominal pain, diarrhea, and nausea. The number of patients developing abnormal liver function tests (including clinically significant elevation), hemoglobin, and creatinine clearance was significantly higher in the oral diclofenac group. CONCLUSION: Application of this topical diclofenac solution to the knee of patients with OA produced relief of symptoms equivalent to oral diclofenac, with minor local skin irritation, but significantly reduced incidence of diclofenac-related GI complaints and abnormal laboratory values.     

Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial

BACKGROUND: Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve the symptoms of osteoarthritis (OA) but can produce harmful systemic effects and end-organ damage. A topical NSAID formulation may provide symptom relief with fewer adverse effects. A new topical diclofenac sodium solution-containing the absorption enhancer dimethyl sulfoxide-was evaluated for the relief of the symptoms of primary OA of the knee. METHODS: A total of 326 patients met entry criteria (including abnormal radiographic findings and flare of pain) and were randomized to receive 40 drops of topical diclofenac solution or a vehicle-control solution, 4 times daily, for 12 weeks. We evaluated 3 primary outcome measures, the Western Ontario McMaster Universities LK3.1 OA Index (WOMAC) pain and physical function subscales and a patient global assessment, and 2 other measures, stiffness and pain on walking, at baseline and after final application. We assessed safety by evaluation of adverse events, vital signs, and irritation at the application site. RESULTS: Topical diclofenac solution was significantly more effective than the vehicle-control solution for all outcome measures; pain, P = .001; physical function, P = .002; patient global assessment, P = .003; stiffness, P = .005; and pain on walking, P = .004. Among patients receiving topical diclofenac, self-limiting minor skin irritation occurred in 68 (41.5%) of 164 patients, including dryness in 60 (36.6%), rash in 18 (11.0%), and paresthesia, pruritus, and vesiculobullous rash in 1 (0.6%) each. There was no significant difference between groups in NSAID-related gastrointestinal tract complaints or in dropouts due to study-related adverse effects. CONCLUSION: Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee, with only minor local irritation and no significant systemic adverse events.     

Efficacy of intra-articular sodium hyaluronate in the treatment of knee osteoarthritis

 To assess the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis, sixty female patients with knee osteoarthritis were randomised to three weekly intra-articular injections of 30 mg sodium hyaluronate (Na HA) with a high molecular weight (1.0 to 2.9 million Da) or 40 mg 6-methylprednisolone acetate (6-MPA). The clinical assessments included pain at rest, at weight-bearing and on walking, Lequesne Index and active range of knee flexion. Assessments were done at baseline, at week 4, and at months 3 and 6. A significant decrease in VAS scores for pain at rest, at weight-bearing and pain on walking, and in Lequesne index was found in both groups at week 4 when compared to baseline and there was no significant differences between the two groups. However, at 3^rd month improvement in all pain scores and Lequesne index was found in favour of hyaluronic acid. At 6^th, no significant difference was found between the treatment groups. Improvement in pain was accompanied by an increase in joint flexion at week 4 and at month 3 in both groups. Both treatments were well-tolerated. The results showed that both intra-articular hyaluronic acid and 6-MPA treatments provide clinically significant improvement and demonstrated that Na HA has a long-term beneficial effect in patients with knee osteoarthritis. Received: 13 May 2002 / Accepted: 21 November 2002     

双醋瑞因治疗老年人痛性膝骨关节炎的疗效和安全性

目的 观察双醋瑞因治疗老年人痛性膝骨性关节炎的疗效及安全性.方法 选择门诊老年痛性膝骨关节炎患者57例,采用随机、阳性药硫酸氨基葡萄糖(维固力)平行对照方法,将57例患者分为双醋瑞因治疗组和维固力对照组,利用100 mm视觉模拟评分表(VAS)评价20 m步行痛积分,骨关节炎指数(WOMAC)评定两组用药前后临床症状改善情况;受试者和医生对总体疗效的评价采用5级评定法,并观察药物不良反应.结果 20 m步行痛积分治疗前、后双醋瑞因组为53.10±17.31和16.73±18.88,维固力组为51.52±18.12和17.33±20.73;WOMAC指数治疗前、后双醋瑞因组为41.13±18.60和18.40±15.70,维固力组为42.81±17.73和21.14±15.60.两组治疗前后比较,差异均有统计学意义(P＜0.05);两组间治疗后比较差异无统计学意义(P＞0.05).受试者对综合有效率评价(5级评定法中:非常好+好+中等):双醋瑞因组为90.0%,维固力组为92.6%;两组患者和医生对疗效的总体评价差异无统计学意义.两组不良反应主要是胃肠道反应,发生率差异无统计学意义.结论 双醋瑞因是治疗老年人痛性膝骨关节炎的有效药物,且具有良好的安全性.     

Topical diclofenac versus placebo: a double blind, randomized clinical trial in patients with osteoarthritis of the knee

OBJECTIVE: To assess the efficacy and safety of a topical formulation of 2% diclofenac in lecithin organogel in the treatment of pain associated with mild to moderate osteoarthritis (OA) of the knee. METHODS: Seventy patients completed a double blind, randomized, placebo controlled, parallel group design 2 week clinical trial. Patient responses to disease-specific (WOMAC VA3.0) and quality of life (Medical Outcome Survey SF-36) health status measures were assessed. Global assessments were also made at baseline and post-treatment. The physician conducted a global assessment and range of motion of the knee at baseline and post-treatment. RESULTS: T tests on the aggregated WOMAC total score and aggregated subscale scores revealed significant improvement (p<0.05) on the aggregated total score and the pain, stiffness, and physical function subscales from baseline to post-treatment for the active treatment group versus the placebo group. Analysis of gain scores from the aggregated WOMAC total score and aggregated subscale scores also revealed that this improvement was significantly greater than the improvement recorded by the placebo treatment group on the aggregated total and the pain and physical function subscale scores. Other efficacy measures exhibited no significant differences between or within treatment groups. CONCLUSION: A topical formulation of 2% diclofenac in a lecithin organogel appears to have therapeutic value in patients with mild to moderate OA of the knee as determined by responses from the WOMAC (VA3.0) osteoarthritis health status measure.     

Efficacy of duloxetine and gabapentin in pain reduction in patients with knee osteoarthritis

Clinical Rheumatology - Knee osteoarthritis (OA) is a common form of arthritis in elders which can lead to reduced daily activity and quality of life. It is important to administer a proper...     

Comparison of aceclofenac with diclofenac in the treatment of osteoarthritis

Summary A multicentre randomised, double-blind, parallel group, general practice study was undertaken to investigate the efficacy and safety of aceclofenac (200 patients, 100mg twice daily and placebo once daily) in comparison with diclofenac (197 patients, 50mg three times daily) in patients with osteoarthritis of the knee. The treatment period of twelve weeks was preceded by a washout period of two weeks duration. At end point, patients in both aceclofenac and diclofenactreated groups exhibited significant improvement in pain intensity (p=0.0001). Although both treatment groups showed significant improvement in all investigators' clinical assessments (joint tenderness, swelling, pain on movement, functional capacity, overall assessment), there were no significant differences between the groups. There was, however, a trend towards greater improvement in complete knee movement and reduced pain on movement with aceclofenac. In patients with initial flexion deformity, aceclofenac was significantly more effective than diclofenac in improving knee flexion after 2–4 weeks of treatment. Patients' subjective assessment of pain relief demonstrated significantly greater efficacy with aceclofenac. At end point, 71% of patients in the aceclofenac group reported improvement in pain intensity as compared to 59% treated with diclofenac (p=0.005). Tolerability of aceclofenac was better than with diclofenac as fewer patients experienced gastrointestinal adverse events. In particular, the incidence of treatment related diarrhoea was less with aceclofenac (1%) than with diclofenac (6.6%). In summary, this study supports a therapeutic role for aceclofenac in arthritis and suggests that it is an alternative NSAID to diclofenac in the treatment of osteoarthritis.     

Topical diclofenac patch in patients with knee osteoarthritis: a randomized,double-blind,controlled clinical trial

OBJECTIVE: To assess the efficacy and safety of a diclofenac hydroxyethylpyrrolidine (DHEP) patch in the treatment of symptomatic osteoarthritis (OA) of the knee joint. METHODS: A double-blind, randomised, placebo-controlled trial was carried out on 103 outpatients for 2 weeks. The main efficacy parameters were spontaneous pain and Lequesne's Index. Secondary endpoints were walking time over a standard distance, global assessment of efficacy and tolerability, and paracetamol consumption. RESULTS: The active treatment group showed a significant improvement in pain, Lequesne's Index, and the physician's and patient's global assessment of efficacy. For these parameters the difference between groups was statistically significant in favour of the DHEP patch. Adverse reactions were seen in a small number of probands and were similar in both groups. CONCLUSIONS: The results of this trial suggest that the DHEP patch appears to be an effective and safe treatment for patients suffering from symptomatic knee OA.     

Paracetamol in osteoarthritis of the knee

BACKGROUND: Paracetamol is a recommended symptomatic treatment of osteoarthritis (OA), but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used. OBJECTIVES: To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment. METHODS: A double blind, parallel group, placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee. Patients were randomly assigned to receive paracetamol 4 g/day (n = 405) or placebo (n = 374) for 6 weeks. Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of >or=30 mm on a 100 mm visual analogue scale. The primary end point was a 30% decrease of global pain intensity of the knee. Intention to treat analyses were performed. RESULTS: The percentage of responders did not differ significantly between groups: 52.6% and 51.9% in paracetamol and placebo groups, respectively (p = 0.840). In a subgroup of patients with chronic mechanical knee pain without signs of inflammation (n = 123), the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm, in the paracetamol (n = 63) and placebo (n = 60) groups, respectively-mean difference 10.0 mm; 95% CI 1.0 to 19.0; p = 0.0294. No serious adverse events were attributable to treatment. CONCLUSION: A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found, suggesting that paracetamol use in symptomatic OA of the knee should be further explored. The tolerability and safety of paracetamol, at the recommended maximum dose of 4 g/day, was confirmed over 6 weeks.     

Total knee arthroplasty for osteoarthritis of the knee

The indication, preoperative condition, surgical technique and postoperative rehabilitation of total knee arthroplasty for osteoarthritis are summarized. I think the point of contributing to the success of total knee arthroplasty are to discuss the preoperative condition, to know well the instrument, to do the accurate osteotomy and to obtain the correct soft tissue balancing.     

Structural factors associated with malalignment in knee osteoarthritis: the Boston osteoarthritis knee study

OBJECTIVE: Osteoarthritis (OA) is a multifactorial condition. The progression of knee OA is determined in part by mechanical effects on local structures. One of the mechanical influences on cartilage loss is limb alignment. We explored the structural factors associated with malalignment in subjects with symptomatic OA. METHODS: We conducted a cross-sectional assessment using The Boston Osteoarthritis of the Knee Study, a natural history study of symptomatic knee OA. Baseline assessments included knee magnetic resonance imaging (MRI) and information on weight and height. Long-limb radiographs to assess mechanical alignment were obtained at 15 months. Subarticular bone attrition, meniscal degeneration, anterior and posterior cruciate ligament integrity, medial and lateral collateral ligament integrity, marginal osteophytes, and cartilage morphology were assessed on MRI using a semiquantitative, multi-feature scoring method (Whole-Organ MRI Score) for whole-organ evaluation of the knee that is applicable to conventional MRI techniques. We also quantified the following meniscal position measures on coronal MRI images in both medial and lateral compartments: subluxation, meniscal height, and meniscal covering of the tibial plateau. Using the long-limb radiographs, mechanical alignment was measured in degrees on a continuous scale. The purpose of this cross-sectional analysis was to determine the individual and relative contribution of various structural factors to alignment of the lower extremity. We assessed the cross-sectional association between various structural factors and alignment of the lower extremity using a linear regression model. RESULTS: The 162 subjects with all measures acquired had a mean age of 67.0 years (SD 9.2), body mass index 31.4 (SD 5.6); 30% were female and 77% of knees had a Kellgren-Lawrence grade > or = 2. The main univariate determinants of varus alignment in decreasing order of influence were medial bone attrition, medial meniscal degeneration, medial meniscal subluxation, and medial tibiofemoral cartilage loss. Multivariable analysis revealed that medial bone attrition and medial tibiofemoral cartilage loss explained more of the variance in varus malalignment than other variables. The main univariate determinants of valgus malalignment in decreasing order of influence were lateral tibiofemoral cartilage loss, lateral osteophyte score, and lateral meniscal degeneration. CONCLUSION: Cartilage loss has been thought to be the major determinant of alignment. We found that other factors including meniscal degeneration and position, bone attrition, osteophytes, and ligament damage contribute to the variance of malalignment. Further longitudinal analysis is required to determine cause and effect relationships. This should assist researchers in determining strategies to ameliorate the potent effects of this mechanical disturbance.