Results of a randomized,dose-ranging trial of etoricoxib in patients with osteoarthritis

OBJECTIVES: To evaluate the clinical efficacy and tolerability of etoricoxib in the treatment of osteoarthritis (OA) of the knee and define the clinically active dose range for further clinical trials. METHODS: This two-part, randomized, double-blind, placebo- and active comparator-controlled trial was conducted in 617 adults with knee OA. In Part 1 (6 weeks), patients received placebo, etoricoxib 5, 10, 30, 60 or 90 mg q.d. In Part 2 (8 weeks), patients received etoricoxib 30, 60 or 90 mg q.d. or diclofenac 50 mg t.i.d., predetermined at Part 1 allocation. Efficacy and safety were evaluated. Primary efficacy end-points were the Western Ontario and McMaster's University Osteoarthritis Index (WOMAC) Pain subscale, Patient Global Assessment of Response to Therapy, and Investigator Global Assessment of Disease Status. RESULTS: At 6 weeks, etoricoxib 5, 10, 30, 60 and 90 mg each demonstrated clinical efficacy superior to placebo. Maximal efficacy was seen with 60 mg. In Part 2, etoricoxib 30, 60 and 90 mg were generally similar to diclofenac. Patients receiving etoricoxib 30, 60 or 90 mg in Parts I and II had sustained effects over 14 weeks. All treatments were well tolerated. CONCLUSIONS: Etoricoxib 60 mg once daily showed maximal efficacy in treating OA in this study. Etoricoxib 5-90 mg once daily was generally well tolerated in OA patients for up to 14 weeks.     

Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies

OBJECTIVE: To compare the efficacy of etoricoxib 30 mg with the generally maximum recommended dose of celecoxib, 200 mg, in the treatment of osteoarthritis (OA) in two identically designed studies. METHODS: Two multi-centre, 26-week, double-blind, placebo-controlled, non-inferiority studies were conducted, enrolling patients who were prior non-steroidal anti-inflammatory drug (NSAID) or acetaminophen users. There were 599 patients in study 1 and 608 patients in study 2 randomized 4:4:1:1 to etoricoxib 30 mg qd, celecoxib 200 mg qd or one of two placebo groups for 12 weeks. After 12 weeks, placebo patients were evenly distributed to etoricoxib or celecoxib based on their initial enrollment randomization schedule. The primary hypothesis was that etoricoxib 30 mg would be at least as effective as celecoxib 200 mg for the time-weighted average change from baseline over 12 weeks for Western Ontario and McMaster (WOMAC) Pain Subscale, WOMAC Physical Function Subscale and Patient Global Assessment of Disease Status. Active treatments were also assessed over the full 26 weeks. Adverse experiences were collected for safety assessment. RESULTS: In both studies, etoricoxib was non-inferior to celecoxib for all three efficacy outcomes over 12 and 26 weeks; both were superior to placebo (P < 0.001) for all three outcomes in each study over 12 weeks. The safety and tolerability of etoricoxib 30 mg qd and celecoxib 200 mg qd were similar over 12 and 26 weeks. CONCLUSIONS: Etoricoxib 30 mg qd was at least as effective as celecoxib 200 mg qd and had similar safety in the treatment of knee and hip OA; both were superior to placebo. ClinicalTrials.gov Identifiers: NCT00092768; NCT00092791.     

Evaluation of the efficacy and safety of etoricoxib compared with naproxen in two, 138-week randomised studies of patients with osteoarthritis

OBJECTIVES: To assess the efficacy and safety of etoricoxib 60 mg once daily and naproxen 500 mg twice daily over a 138-week treatment period in patients with osteoarthritis (OA). METHODS: Two 1-year randomised, double blind, parallel group two-part base studies (part I 12 weeks; part II 40 weeks), followed by an 86-week extension, in patients with OA (hip or knee) were conducted at 80 clinical centres (19 countries). The studies had identical designs. Patients taking placebo in part I received etoricoxib or naproxen (1:1 ratio) in part II and the extension; patients taking etoricoxib or naproxen in part I continued to receive the same treatment throughout the entire length of the studies. Co-primary efficacy end points were patient global assessment of disease status, and WOMAC questionnaire pain subscale and physical function subscale (100 mm VAS). Efficacy over 138 weeks was assessed by graphical analysis. Safety was assessed by observation of adverse experiences and laboratory and physical evaluations. RESULTS: 997 patients entered (615 completed) the base studies. Of these patients, 463 patients entered the extensions. A total of 161 and 152 patients in the etoricoxib and naproxen groups, respectively, completed 138 treatment weeks. Etoricoxib and naproxen showed similar efficacy throughout the 138 weeks of treatment. For etoricoxib and naproxen, respectively, WOMAC pain assessments were 67 and 67 mm (baseline); 28 and 29 mm (1 year), and 34 and 33 mm (138 weeks). Results for the other efficacy end points were similar to those seen with the WOMAC pain assessments. Both etoricoxib and naproxen were generally well tolerated. CONCLUSION: Both etoricoxib and naproxen demonstrated long-term clinical efficacy for the treatment of OA. Etoricoxib and naproxen were generally well tolerated.     

Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures.

OBJECTIVES: Why some patients with knee osteoarthritis (OA) report greater pain severity than others is unclear. We examined the demographic variables, psychosocial variables, and physical findings that predict severity of pain in patients with symptomatic knee OA comparing 3 different pain scales. METHODS: Pain severity was measured in 68 outpatients with knee OA using the WOMAC OA Index, the McGill Pain Questionnaire (MPQ), and a 0-100 visual analog scale (VAS). Depression, anxiety, fatigue, helplessness, self-efficacy, and quality of life were measured using standard instruments. Pain threshold was measured by dolorimetry and a standard knee examination performed. Radiographs were viewed when available. RESULTS: Significant correlations (r = 0.39-0.61) were found between pain measures. In unadjusted analysis, BMI and helplessness correlated with all 3 scales; race, education, female sex, and osteophyte score also correlated with at least one instrument. Depression, anxiety, and fatigue correlated only with the MPQ. Age, duration, and quality of life were not related to pain severity. After adjusted analysis the following variables remained: education, helplessness, and osteophyte score (WOMAC); BMI and helplessness (MPQ); duration, education, helplessness, and osteophyte score (VAS). "Sitting pain" and "night pain" had different associations from pain on walking, standing, or using stairs. CONCLUSION: Different pain scales measure different facets of the pain experience in knee OA and cannot be used interchangeably. The WOMAC pain scale has advantages over other instruments. Helplessness, education, and BMI appear to be important, potentially treatable, factors in determining self-reported pain severity in knee OA: other associations vary with both the pain scale used and the situation in which pain occurs, supporting the hypothesis that pain in knee OA is heterogeneous.     

Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee

OBJECTIVE: Pain is the cardinal feature of osteoarthritis (OA), and with advancing disease there is loss of function and increasing pain even at times of joint rest. Few studies have evaluated the role of opioid analgesics in treating the pain of OA. METHODS: This randomized, double blind, parallel group study compared the efficacy and safety of a 12 hourly controlled release codeine formulation (Codeine Contin) with placebo in patients with chronic pain due to OA of the hips and/or knees. The 4 week treatment period, following an analgesic washout phase of 2-7 days, included weekly clinic evaluations, at which the dose was escalated as appropriate, and daily patient diary completion. Pain (daily), stiffness, and physical function (weekly) were assessed using the multidimensional, self-administered WOMAC (visual analog scale version) questionnaire. RESULTS: Sixty-six eligible patients completed the study. The mean initial and final daily doses of controlled release codeine were 50 mg every 12 h at baseline and 159 mg every 12 h at the final assessment. All variables in the efficacy analysis indicated superiority of controlled release codeine over placebo. The WOMAC pain scale showed an improvement of 44.8% over baseline in the controlled release codeine group compared with 12.3% taking placebo (p = 0.0004). For the WOMAC stiffness and physical function scales the improvements over baseline on controlled release codeine were 47.7% and 49.3%, respectively compared with 17.0% and 17.0%, respectively, with placebo (p = 0.003; p = 0.0007). Controlled release codeine was also significantly better than placebo on measures of sleep quality and requirement for supplemental acetaminophen. CONCLUSION: Single entity controlled release codeine is an effective treatment for pain due to OA of the hip or knee.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial

OBJECTIVE: Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study. METHODS: The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group. CONCLUSION: TDF can reduce pain and improve function in patients with knee or hip OA.     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized,placebo‐controlled trial

Objective

Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.

Methods

The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.

Conclusion

TDF can reduce pain and improve function in patients with knee or hip OA.

     

A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee

OBJECTIVE: To assess prospectively the efficacy and tolerability of hylan G-F 20 (HG-F 20; Synvisc) and intraarticular triamcinolone hexacetonide (TH; Aristospan) for treatment of osteoarthritis (OA) knee pain in a 26 week, randomized, multicenter, evaluator-blind study. METHODS: Patients with OA were treated with typical regimens of HG-F 20 (n = 113) and TH (n = 102). Primary assessments were the WOMAC question A1 (pain walking on a flat surface), and a 100 mm visual analog scale (VAS) for patient and investigator overall assessments. Total WOMAC and WOMAC domain C (function) scores were also assessed. The intent-to-treat population was analyzed using a last-observation carried forward approach. RESULTS: Maximum pain relief occurred at 1-2 weeks for TH and at Week 12 for HG-F 20. At Weeks 12 and 26, HG-F 20 was significantly better than TH for the WOMAC question A1 responses (p = 0.0071 and p = 0.0129, respectively), and patient VAS (p < 0.0001 and p < 0.0001) and investigator VAS (p < 0.0300 and p = 0.0004) assessments. Similar significant (p < 0.01) results were observed at Weeks 12 and 26 for total WOMAC and domain C scores. While 15 TH-treated patients discontinued the study due to lack of efficacy, none did so with HG-F 20 treatment (p < 0.01). Both agents were well tolerated with similar adverse event profiles. CONCLUSION: Viscosupplementation with HG-F 20 resulted in a longer duration of effect than TH with a comparable tolerability profile. These data support the preferential use of HG-F 20 over TH for treatment of chronic OA knee pain.     

Role of the Nav1.7 R1150W amino acid change in susceptibility to symptomatic knee osteoarthritis and multiple regional pain

Objective

To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the α‐subunit of the voltage‐gated sodium channel Na_V1.7.

Methods

Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy‐six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed‐effects meta‐analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes.

Results

No association with the WOMAC was seen in the UK cohorts. Overall, the meta‐analysis of WOMAC yielded a summary statistic of β = 0.47 (95% confidence interval [95% CI] 0.04, 0.89; P = 0.030) for the variant allele. The meta‐analysis of symptomatic versus asymptomatic OA did not demonstrate an association with rs6746030 (odds ratio [OR] 0.90 [95% CI 0.71, 1.15], P = 0.38). The meta‐analysis of multiple regional pain resulted in a significant OR of 1.40 (95% CI 1.08, 1.80; P = 0.0085). No interstudy heterogeneity was seen for any of the analyses.

Conclusion

We find evidence that the R1150W amino acid change in the Na_V1.7 α‐chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA‐specific pain.     

Efficacy and safety of diacerein in osteoarthritis of the knee: a randomized,multicenter, double‐dummy,diclofenac‐controlled trial in China

Aim: To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods: A total of 223 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 17‐week, randomized, double‐dummy, diclofenac‐controlled trial, with diacerein dosages of 100 mg/day and diclofenac sodium administered at 75 mg/day. Result: After 12 weeks of treatment, the total efficacy rates of patient/physician global assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2% respectively (P > 0.05). In the intent‐to‐treat population, the primary criterion (visual analogue scale [VAS] assessment of pain on walking 20 m) was significantly superior (P < 0.05) to baseline in both two groups. Significant improvement (P < 0.05) was also observed for the secondary criteria, which included tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short‐Form Health Survey (SF‐36). In the follow‐up period, there were no obvious changes in the above parameters in the diacerein group. However, in the diclofenac group, pain on walking 20 m, tenderness on palpation and WOMAC became worse after withdrawing the medications for 4 weeks. Moreover, the consumption of paracetamol was significantly lower in the diacerein group than in the diclofenac group during the follow‐up period. The incidence of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group (P > 0.05). Mild‐to‐moderate gastrointestinal disorders were the most frequent adverse events. Conclusion: Diacerein was shown to be as effective as diclofenac sodium in treating patients with knee OA, coupled with a carry‐over effect. Diacerein was generally well tolerated, with a good safety profile. No severe adverse events were occurred.     

A comparison of muscle training methods in patients with knee osteoarthritis

This study sought to compare the efficacy of isokinetic and progressive resistive exercise (PRE) programs in patients with knee osteoarthritis (OA). Forty-four patients with bilateral knee OA were included in the study. The patients in Group 1 (n=21) performed isokinetic exercises and the patients in Group 2 (n=18) performed a PRE program. Disease severity, pain, walking time, WOMAC, Lequesne index, AIMS2 and SF36 were compared before and after the treatments. All the patients were evaluated via a Cybex isokinetic device before and after treatment. Disease severity, pain, Lequesne, WOMAC and walking time improved with treatment in both groups. In SF36 and AIMS2 assessments, pain and social evaluation parameters in the PRE group showed better improvement. On isokinetic assessment flexor and extensor peak torque and peak torque body weight values improved significantly in both groups compared to pretreatment measurements. When the assessed parameters were taken into account no statistical significant difference was observed between the two groups. Our conclusions were that isokinetic and PRE programs are efficient in the treatment of knee OA; no statistically significant differences could be found between the two programs; and the PRE program, as it is cheaper, more easily performed and efficient, may be preferable for the treatment of knee OA.Abbreviations OA Osteoarthritis - PRE Progressive resistive exercise - PT Peak torque - PTBW Peak torque body weight - ROM Range of motion - TW Total work - TWBW Total work body weightAn erratum to this article can be found at     

Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial

Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; p<0.0001); mean change in pain intensity was a reduction of greater than 2 (p<0.0001); almost 50% were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (p<0.0001). Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score, individual pain, stiffness and physical function sub-scores (p<0.0001). AEs causing discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life in these patients. The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub-population of patients with OA pain.     

Knee vs hip single-joint intra-articular hyaluronic acid injection in patients with both hip and knee osteoarthritis: a pilot study

This paper aims to compare the results of single-joint knee vs hip hyaluronic acid (HA) injections in patients with osteoarthritis (OA) involving both the knee and hip joints. Thirty-eight patients who were diagnosed to have both hip and knee OA were enrolled. Patients were divided into two groups to receive HA injection three times at 1-week intervals either to the hip or knee joints. Pain level during activities and rest was measured by using visual analog scale (VAS). Western Ontario and McMaster University Osteoarthritis Index (WOMAC 5-point Likert 3.0) was also used prior to the injections and 1 month after the 3rd injection. In the knee injection group, the intragroup analysis revealed significant improvements in VAS activity pain, VAS rest pain, and WOMAC pain values following injection when compared with preinjection values, while no significant difference was detected in WOMAC stiffness, WOMAC physical function, and WOMAC total values. In the hip injection group, VAS activity pain, VAS rest pain, WOMAC pain, WOMAC stiffness, WOMAC physical function, and WOMAC total values showed significant improvement after the injection when compared with preinjection values. Although statistically not significant (p > 0.05), the comparison of the differences (preinjection–postinjection) between the groups demonstrated higher values in the hip injection group. We imply that intra-articular single-joint HA injections either to the knee or hip joints in OA patients with involvement of both of these joints are effective with regard to pain and functional status.     

Effectiveness of a home-based exercise therapy and walking program on osteoarthritis of the knee

Osteoarthritis (OA) of the knee is a very common rheumatological disease, and there are various treatment modalities for it. The aim of this study was to investigate the effects of home-based exercise and walking programs in the treatment of OA. A total of 90 patients with knee osteoarthritis were included. Their ages ranged between 48 and 71 years. The patients were separated into three groups. None of them had practiced a daily simple exercise program during the previous year. Group 1 ( n=30) was given a home-based exercise program. Group 2 ( n=30) had regular a walking program three times per week, starting with 10-min duration. Group 3 ( n=30) was accepted as the control group. Patients were assessed according to pain, functional capacity, and quality of life parameters. Pain was evaluated by the Western Ontario McMaster osteoarthritis index (WOMAC) of pain score and visual analogue scale (VAS). Functional capacity was measured by WOMAC physical function index. Quality of life was assessed by the Nottingham Health Profile questionnaire (NHP). All groups continued the program for 3 months. At the end of the therapy, the patients were called and 81 were accepted to come to the hospital. Although WOMAC pain and physical functional scores and VAS scores were statistically lower in both groups than in the control group ( P<0.001), the difference between groups 1 and 2 was not statistically significant ( P>0.05). But the result of the NHP showed a statistically significant improvement in the walking group when compared to the home-based exercise and control groups ( P<0.001). As a result, we conclude that a simple home-based exercise therapy and a regular walking program are effective in treating the symptoms of OA.     

Gastrointestinal side effects of etoricoxib in patients with osteoarthritis: results of the Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) trial

OBJECTIVE:. To compare the gastrointestinal (GI) tolerability, safety, and efficacy of etoricoxib and diclofenac in patients with osteoarthritis (OA). METHODS: In total, 7111 patients (mean age 64 yrs) diagnosed with OA were enrolled in a randomized, double-blind trial. Patients received etoricoxib 90 mg qd (n = 3593) or diclofenac sodium 50 mg tid (n = 3518). Gastroprotective agents and low-dose aspirin were prescribed per treatment guidelines. The primary endpoint was the cumulative rate of discontinuations due to clinical and laboratory GI adverse experiences (AE). General safety was assessed, including adjudication of thrombotic cardiovascular (CV) safety data. Efficacy was evaluated using the least-square (LS) mean change from baseline patient global assessment of disease status (PGADS; 0-4 point scale). RESULTS: Mean (SD, maximum) duration of treatment was 9.3 (4.4, 16.5) and 8.9 (4.5, 16.6) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AE was significantly lower with etoricoxib than diclofenac [9.4 vs 19.2 events per 100 patient-years (PY), respectively; hazard ratio (HR) 0.50 (95% CI 0.43, 0.58; p < 0.001). Rates of thrombotic CV events were similar with etoricoxib and diclofenac [1.25 vs 1.15 events per 100 PY, respectively; HR 1.07 (95% CI 0.65, 1.74)]. The incidence of patients who discontinued due to hypertension-related AE was significantly higher with etoricoxib compared to diclofenac (2.3% vs 0.7%; p < 0.001), although few AE were severe (3 etoricoxib, 1 diclofenac). Etoricoxib and diclofenac treatment resulted in similar improvements in PGADS from baseline of -0.78 (95% CI -0.80, -0.75) and -0.75 (95% CI -0.77, -0.72), respectively. CONCLUSION: Treatment with etoricoxib 90 mg was associated with significantly better GI tolerability compared to diclofenac in this population of patients with OA. Etoricoxib 90 mg, a dose 50% higher than indicated for OA, resulted in more discontinuations due to hypertension-related AE.     

Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: A randomized,double‐blind,placebo‐controlled trial

Objective

To evaluate the safety and efficacy of long‐term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).

Methods

In a randomized, double‐blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50‐foot walking time. Clinical symptoms were assessed just before each injection.

Results

At the 1‐year and 2‐year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid‐injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline‐injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2‐year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).

Conclusion

Our findings support the long‐term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long‐term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long‐term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.

     

Steroid injection for osteoarthritis of the hip: A randomized,double‐blind,placebo‐controlled trial

Objective

To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double‐blind, placebo‐controlled trial.

Methods

Fifty‐two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100‐mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100‐mm VAS), and Short Form 36 (SF‐36) quality of life indices. Analyses were based on the intent‐to‐treat principle.

Results

The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF‐36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups.

Conclusion

This placebo‐controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.

     

Randomized double‐blind clinical drug trials of meloxicam in rheumatoid arthritis and osteoarthritis knees: an Indian experience

Background: Indian data from controlled drug trials on the use of meloxicam (a new preferential COX‐2 inhibitor) and other non‐steroidal anti‐inflammatory drugs (NSAIDs) in arthritis is sparse. Aim: To evaluate the clinical efficacy and safety of meloxicam. Patients and methods: One hundred and twenty‐one patients with rheumatoid arthritis (RA) and 133 patients with osteoarthritis (OA) knees were randomized into two different multicentric, double‐blind, drug trials of four‐weeks duration each. Meloxicam 7.5 mg (OA study) and 15 mg (RA study) was compared to diclofenac 100 mg and piroxicam 20 mg in daily dosages, respectively. Strict eligibility criteria ensured active symptomatic disease. Standard ACR efficacy measures of pain and function (including validated Indian versions of HAQ & WOMAC) were used. Protocol‐driven evaluations were carried out throughout the study. An intent‐to‐treat efficacy analysis (significance at P < 0.05) was carried out to test the hypothesis of equal efficacy between meloxicam and comparator. Results: (i) There were no significant differences between meloxicam and piroxicam in the RA study. (ii) While joint count for pain/tenderness was improved (P < 0.05) by both meloxicam and piroxicam, only meloxicam showed significant improvement (95% CI ≈ 0.7,5.6) in swollen joint count. (iii) In the OA study, though painVAS reduction was marginally better (95% CI ≈ ?15,?0.6) with diclofenac, both meloxicam and diclofenac were equally effective (95% CI ≈ ?10,2.0) in improving WOMAC‐physical function. (iv) Overall, meloxicam demonstrated a superior safety and gut tolerability profile as compared to piroxicam (maximum adverse events, 29.3%) and diclofenac. (iv) Maximum dyspepsia (6.2%) was reported by the diclofenac group. (v) Overall, the drug toxicity seen in the trials was mild, and only one patient (on diclofenac) was withdrawn due to haematuria. (vi) All treatment groups consumed paracetamol (P > 0.05) as a rescue analgesic. Conclusions: When compared to piroxicam and diclofenac, meloxicam has equal clinical efficacy and a better safety profile. Multicentric control drug trials are feasible in our population.