Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a prospective randomized 13-week study versus placebo and celecoxib

The objective of this study was to evaluate the efficacy, safety and tolerability of lumiracoxib compared with placebo and celecoxib in patients with osteoarthritis (OA). Following a 3- to 7-day washout period for previous non-steroidal anti-inflammatory drugs, 1600 patients aged 18 years with primary knee OA were randomized to receive lumiracoxib 200 or 400 mg once daily (o.d.), celecoxib 200 mg o.d. or placebo for 13 weeks. Primary efficacy variables were OA pain intensity in the target knee, patients global assessment of disease activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total scores at week 13. Secondary variables included OA pain intensity in the target knee and physicians and patients global assessments of disease activity by visit. Exploratory analysis of responder rates using the Outcomes Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria was performed. Safety and tolerability were assessed. Lumiracoxib was superior to placebo in all primary and secondary variables and was generally similar to celecoxib. There were no statistically significant differences between the two doses of lumiracoxib. All active treatments were significantly more effective than placebo at weeks 2 and 13 in terms of response to treatment assessed using OMERACT-OARSI criteria. The incidence of adverse events was similar across the groups. Lumiracoxib 200 mg o.d. is a well-tolerated and effective treatment option for OA of the knee, providing pain relief and improved functional status with efficacy superior to placebo and similar to celecoxib. Lumiracoxib demonstrated a tolerability profile similar to placebo and celecoxib.     

Long-term efficacy and safety of lumiracoxib 100 mg: an open-label extension of a 13-week randomized controlled trial in patients with primary osteoarthritis of the knee

OBJECTIVE: Osteoarthritis (OA) is a chronic condition, accompanied by inflammation and pain, and it is therefore important to demonstrate long-term efficacy and safety of treatment. Here we present data from a 39-week open-label extension to a 13-week randomized, double-blind, double-dummy, parallel-group core study. The objective was to assess the long-term safety and tolerability of lumiracoxib 100 mg once daily (od).METHODS:Patients had originally received lumiracoxib 100 mg od, celecoxib 200 mg od or placebo in the core study. In the extension period, all patients received lumiracoxib 100 mg od. Efficacy variables, overall OA pain intensity (0-100 mm visual analogue scale [VAS]), patient's global assessment of disease activity and physician's global assessment of disease activity (0-100 mm VAS), were assessed at weeks 17, 26, 39 and 52. General safety and tolerability were evaluated by adverse event (AE) reporting and physical examinations and laboratory tests at each visit. RESULTS:Of the 1182 patients completing the core study, 834 patients entered the extension study. Improvements in the three efficacy variables after 3 months were maintained for up to 1 year with lumiracoxib treatment. Lumiracoxib was well tolerated, with most AEs being of mild-to-moderate severity and of the type expected for this patient population and duration of exposure.CONCLUSION:In conclusion, these data suggest that lumiracoxib 100 mg od was effective and well tolerated when treating OA pain of the knee for periods of up to 1 year, making it a useful option for the long-term treatment of OA pain.     

Efficacy and tolerability of lumiracoxib versus placebo in patients with osteoarthritis of the hand

OBJECTIVE: This multicentre, randomized, double-blind, placebo-controlled parallel-group study was undertaken to investigate the efficacy, safety and tolerability of lumiracoxib (Prexige), a cyclooxygenase-2 selective inhibitor, in patients with primary osteoarthritis (OA) of the hand. METHODS: The study randomized 594 patients aged > or = 18 years with symptomatic OA of the hand. Patients underwent a 3 to 7-day washout for previous nonsteroidal anti-inflammatory drugs and those with pain intensity > or = 40 mm on a 100 mm Visual Analogue Scale (VAS) in the target hand during the 24 hours prior to baseline and an increase in pain intensity of either > or = 20% or > or = 10 mm VAS since screening (whichever was greater) were randomized to lumiracoxib 200 mg once daily (od) (n=205), lumiracoxib 400 mg od (n=193) or placebo (n=196). The primary efficacy variable was overall OA pain intensity (VAS mm) in the target hand after 4 weeks of treatment. Safety and tolerability assessments were performed. RESULTS: After 4 weeks of treatment, overall OA pain intensity in the target hand was significantly lower for patients treated with lumiracoxib compared with patients treated with placebo (both doses p<0.001). There was no significant difference between lumiracoxib doses in terms of the reduction in overall OA pain intensity. Lumiracoxib was well tolerated. The incidence of adverse events was similar for active treatment groups and placebo. CONCLUSIONS: Lumiracoxib 200 and 400 mg od were effective and well tolerated treatments for OA of the hand. Lumiracoxib significantly improved overall OA pain intensity in the target hand versus placebo, with a tolerability profile similar to placebo.     

A 13-week,multicenter, randomized,double-blind study of lumiracoxib in hip osteoarthritis

The aim of this 13-week, multicenter, randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was to demonstrate the efficacy, safety, and tolerability of lumiracoxib in primary hip osteoarthritis (OA) patients. Eligible patients (n = 1,262; ACR criteria) were randomized (1:1:1) to receive lumiracoxib 100 mg once daily (o.d.) (n = 427), celecoxib 200 mg o.d. (n = 419), or matching placebo o.d. (n = 416) administered orally. The primary objective was to compare lumiracoxib 100 mg o.d. and placebo with respect to three co-primary efficacy variables: the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 (WOMAC™ LK 3.1) questionnaire, the function subscale of the WOMAC™ LK 3.1 questionnaire, and patient’s global assessment of disease activity (100-mm visual analog scale (VAS)) after 13 weeks of treatment. Of the 1,262 randomized patients, 951 completed the study. All randomized patients were included in the intention-to-treat and safety populations. Lumiracoxib was superior to the placebo (p < 0.001) after 13 weeks for all three co-primary endpoints. By week 13, the patient’s global assessment of disease activity (100-mm VAS) improved by 23.3 mm (±SD, 27.83 mm) with lumiracoxib and 13.3 mm (±26.71 mm) with placebo. The WOMAC™ function score decreased by 10.4 (±13.56) with lumiracoxib and 6.8 (±12.55) with placebo. The WOMAC™ pain scores decreased by 3.4 (±4.16) with lumiracoxib and 2.2 (±3.94) with placebo at week 13. Similar results were observed for secondary endpoints: OA pain intensity and WOMAC™ total score. Lumiracoxib was similar to celecoxib for all three co-primary endpoints. All treatments were well tolerated. In conclusion, lumiracoxib is effective in reducing pain and improving function in hip OA patients. Clinical trial registration information: ; NCT00154219     

Efficacy of lumiracoxib in relieving pain associated with knee osteoarthritis: a 6‐week,randomized, double‐blind,parallel‐group study

Aim: The aim of the current study was to assess the efficacy, safety, and tolerability of lumiracoxib 200 mg once daily (o.d.) in relieving osteoarthritis (OA) knee pain in patients in China, Taiwan, and South Korea. Methods: Patients of either sex (aged ≥ 18 years) with symptomatic, primary OA of the knee for ≥ 3 months were eligible for inclusion if they had OA pain intensity of ≥ 40 mm (100 mm visual analogue scale [VAS]) in the target knee joint during the previous 24 h. Patients were required to undergo regular non‐steroidal anti‐inflammatory drug therapy for ≥ 6 weeks. After 3–7 days of screening, patients were randomized (1 : 1) to receive either lumiracoxib 200 mg o.d. or celecoxib 200 mg o.d. The primary efficacy comparison between the study groups was overall OA pain intensity (VAS) in the target knee after 6 weeks of treatment. Results: The mean overall OA pain intensity (VAS) in the target knee after 6 weeks decreased from 60.6 mm to 35.7 mm and 60.5 mm to 36.1 mm in the lumiracoxib and celecoxib groups, respectively. Both study groups showed similar results in terms of improvement in both patient's and physician's global assessment of disease activity and functional health status. The percentage of adverse events (AEs) in the lumiracoxib and celecoxib groups (40.3% and 37.9%, respectively) was similar, as was the proportion of treatment‐related AEs (21.0% and 18.2%, respectively). Conclusions: Lumiracoxib 200 mg o.d. provided effective and well‐tolerated pain relief similar to that achieved with celecoxib 200 mg o.d. in knee OA patients.     

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: a phase II, four-week, multicenter, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To compare the efficacy and tolerability of the novel cyclooxygenase 2-selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA). METHODS: Adults (n=583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting. RESULTS: All lumiracoxib doses were superior to placebo in relieving pain, improving stiffness, and improving physical function after 4 weeks. At study endpoint, pain relief was comparable among all lumiracoxib dosages and similar to diclofenac. Lumiracoxib tolerability was superior to diclofenac and comparable to placebo. CONCLUSION: Lumiracoxib provides predictable and sustained relief from pain, stiffness, and impaired physical function in OA. Lumiracoxib shows clinically comparable efficacy and superior tolerability to diclofenac.     

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: A phase II,four‐week,multicenter, randomized,double‐blind,placebo‐controlled trial

Objective

To compare the efficacy and tolerability of the novel cyclooxygenase 2‐selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA).

Methods

Adults (n = 583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting.

Results

All lumiracoxib doses were superior to placebo in relieving pain, improving stiffness, and improving physical function after 4 weeks. At study endpoint, pain relief was comparable among all lumiracoxib dosages and similar to diclofenac. Lumiracoxib tolerability was superior to diclofenac and comparable to placebo.

Conclusion

Lumiracoxib provides predictable and sustained relief from pain, stiffness, and impaired physical function in OA. Lumiracoxib shows clinically comparable efficacy and superior tolerability to diclofenac.

     

Efficacy and safety of PG201 (Layla®) and celecoxib in the treatment of symptomatic knee osteoarthritis: a double-blinded,randomized, multi-center,active drug comparative,parallel-group,non-inferiority,phase III study

The objectives of the study are to demonstrate the non-inferiority of PG201 (Layla^®) 600 mg in comparison with celecoxib 200 mg for the treatment of symptomatic knee osteoarthritis (OA). In total, 309 patients were randomly assigned to receive either the test drug, PG201 600 mg (n = 154) or celecoxib 200 mg (n = 155). The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit (week 8), and this value was compared between the 2 treatment groups. Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain VAS score and subscale score, patient’s global assessment of disease status quality of life (short form-36) and responder index at weeks 4 and 8. For safety assessment, adverse events were recorded at each clinical visit. At weeks 8, the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600 mg (p < 0.0001) and celecoxib 200 mg (p < 0.0001) as compared to the baseline scores; however, no statistically significant differences in these values were noted between the groups (p = 0.312). These results met pre-specified criteria for non-inferiority for both the intent-to-treat and per-protocol populations. PG201 600 mg and celecoxib 200 mg were both well tolerated and no statistically significant differences in the tolerability profile between the groups. PG201 600 mg was as effective and safe as celecoxib 200 mg in the treatment of symptomatic knee OA and might be a useful new medication for the treatment of symptomatic knee OA.     

A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee

OBJECTIVE: To assess the efficacy of intraarticular (IA) injections of hyaluronic acid (HA) compared to placebo in patients with osteoarthritis (OA) of the knee; and to assess patient satisfaction with treatment relative to placebo, and whether there is a difference between a series of 3 versus 6 consecutive IA injections. METHODS: We conducted a randomized, double-blind, placebo controlled, 2-arm parallel design trial of 106 patients with radiologically confirmed knee OA. Two-milliliter IA injections using 20 mg/ml HA sodium salt or saline placebo were administered once weekly over 3 weeks (HA and placebo groups), followed by once weekly IA injection with 2.0 ml (20 mg/ml) HA for a further 3 consecutive weeks. The primary efficacy assessment included Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score for knee pain (Week 3 score). Secondary efficacy assessments included WOMAC scores for knee pain at Weeks 6 and 12 (followup), as well as WOMAC stiffness, physical function and quality of life scores, visual analog scale (VAS) scores for pain at rest and following walking and stepping activity, range of knee joint motion, and global patient satisfaction with treatment and quality of life using the SF-36. RESULTS: After 3 weeks of study treatment, both treatment groups showed improvements in knee function, the HA group showing a greater improvement compared to placebo in WOMAC knee pain score (p < 0.01). The HA group showed greater (p < 0.05) improvement in the overall WOMAC score and VAS pain following walking and stepping activity at Week 3. Results from all other secondary efficacy assessments at Weeks 6 and 12 including patient satisfaction were similar and were not statistically significant between treatment groups, and there were no significant differences between groups for adverse events. CONCLUSION: Intraarticular HA was superior to placebo in improving knee pain and function, with no difference between 3 or 6 consecutive injections for the primary efficacy assessment.     

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.     

Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis

OBJECTIVE: To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis (AS). METHODS: This was a 12-week randomized, double-blind, placebo-controlled study with 4 treatment arms: celecoxib 200 mg qd, celecoxib 400 mg qd, naproxen 500 mg bid, and placebo. Patients (age 18-75 yrs) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs, and with a pain intensity on visual analog scale (VAS) > or = 50 mm worsening by 30% compared with a preinclusion visit (14 days prior) were studied. Primary endpoints were least-squares mean changes from baseline in pain intensity, disease activity (patient global assessment VAS), and functional impairment [Bath Ankylosing Spondylitis Functional Index (BASFI)]. Adverse events were monitored throughout the study. RESULTS: Of 611 randomized patients, 137 were allocated to celecoxib 200 mg, 161 to celecoxib 400 mg, 157 to naproxen, and 156 to placebo. Improvements in least-squares mean pain intensity, disease activity, and BASFI scores were significantly greater in the celecoxib 200 mg, celecoxib 400 mg, and naproxen groups than in the placebo group (p < or = 0.001) at Week 12 and the interim timepoints, Weeks 1, 3, and 6. Celecoxib 400 mg was as effective as naproxen; however, naproxen was more effective than celecoxib 200 mg. Celecoxib was well tolerated, with an adverse event profile similar to placebo. However, 3 naproxen-treated patients experienced serious treatment-related gastrointestinal (GI) adverse events (one severe gastric ulcer, one moderate GI hemorrhage, one severe GI hemorrhage). CONCLUSION: In this 12-week study, celecoxib 200 mg qd and 400 mg qd were efficacious and well tolerated in treating signs and symptoms of AS.     

Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial

OBJECTIVE: To compare epicutaneous ketoprofen in Transfersome (ultra-deformable vesicles, IDEA-033) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis. METHODS: This was a multicentre, randomised, double-blind, controlled trial; 397 patients with knee osteoarthritis participated and 324 completed the trial. They were randomly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (n = 138), 100 mg oral celecoxib plus placebo gel (n = 132), or both placebo formulations (n = 127) twice daily for 6 weeks. Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale, physical function subscale and patient global assessment (PGA) of response. RESULTS: The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 (95% confidence interval -22.1 to -14.3), 20.3 (-24.3 to -16.2) and 9.9 (-13.9 to -5.8) in the IDEA-033, celecoxib and placebo groups, respectively, and the physical function subscale score by 14.6 (-18.1 to -11.0), 16.6 (-20.2 to -13.0) and 10.2 (-13.8 to -6.6), respectively. The mean PGA of response scores were 1.8 (1.6 to 2.1), 1.7 (1.5 to 1.9) and 1.3 (1.1 to 1.5), respectively. The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (p<0.01) and PGA of response (p<0.01). Gastrointestinal adverse events for IDEA-033 were similar to placebo. CONCLUSION: IDEA-033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis.     

Efficacy and safety of diacerein in osteoarthritis of the knee: a double-blind, placebo-controlled trial. The Diacerein Study Group

OBJECTIVE: To evaluate the efficacy and safety of diacerein, a drug with interleukin-1beta--inhibitory activity in vitro, in patients with knee osteoarthritis (OA). METHODS: A total of 484 patients fulfilling the American College of Rheumatology criteria for knee OA were enrolled in this 16-week, randomized, double-blind, placebo-controlled, parallel study group with 3 diacerein dosages of 50 mg/day, 100 mg/day, and 150 mg/day (administered twice daily). RESULTS: In the intent-to-treat population, 100 mg/day diacerein (50 mg twice daily) was significantly superior (P < 0.05) to placebo using the primary criterion (visual analog scale [VAS] assessment of pain on movement). Significant improvement (P < 0.05) was also observed for the secondary criteria, which included the Western Ontario and McMaster Universities OA Index (WOMAC), the WOMAC subscores, and the VAS assessment of handicap. In patients treated with diacerein dosages of 50 mg/day and 150 mg/day, favorable but not significant results were observed for the primary criterion. The best daily dosage of diacerein, calculated from the effect on the VAS assessment of pain on movement, was 90.1 mg. In the per-protocol population, the analysis of the primary criterion showed significant dose-dependent differences (P < 0.05) between each of the 3 diacerein dosages and the placebo. No differences were observed among the 3 diacerein groups. A significantly higher incidence (P < 0.05) of adverse events (AEs), as well as a higher rate of dropoout due to AEs, was observed in patients treated with 150 mg/day diacerein versus those treated with placebo, 50 mg/day diacerein, or 100 mg/day diacerein. Mild-to-moderate transient changes in bowel habits were the most frequent AEs, increasing with the dosage. CONCLUSION: Diacerein, a drug for the treatment of OA, was shown to be an effective treatment for symptoms in patients with knee OA. Taking into account both efficacy and safety, the optimal daily dosage of diacerein for patients with knee OA is 100 mg/day (50 mg twice daily).     

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.     

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.     

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.

     

Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) as add-on therapy for subjects with osteoarthritis (OA) pain inadequately controlled by COX-2 nonsteroidal antiinflammatory drugs (NSAID). METHODS: This 91-day, multicenter, randomized, double-blind, placebo-controlled trial enrolled subjects with symptomatic OA for >/= 1 year who experienced at least moderate pain [visual analog scale (VAS) score >/= 50/100 mm] despite treatment with stable doses of celecoxib (>/= 200 mg/day) or rofecoxib (>/= 25 mg/day). Tramadol/APAP or matching placebo was titrated to 4 tablets/day on Day 10 and thereafter as needed up to 8 tablets/day. The primary efficacy measure was final VAS score; secondary measures included final pain relief rating scores, subject/investigator overall medication assessments, rate and time to discontinuation due to lack of efficacy, and selected quality-of-life/physical functioning scores. RESULTS: Of 307 subjects randomized, 306 taking celecoxib (56.5%) or rofecoxib (43.5%) were included in the intent-to-treat population (n = 153 tramadol/APAP, 153 placebo). Mean final VAS scores for tramadol/APAP plus COX-2 NSAID were significantly lower than placebo plus COX-2 NSAID (41.5 vs 48.3; p = 0.025) and mean final pain relief rating scores were significantly higher (p = 0.002). Subjects taking tramadol/APAP showed significant improvements compared with placebo in subject/investigator medication assessments, as well as in the WOMAC Physical Function and the Medical Outcome Study Short Form-36 Role-Physical measures. The most common treatment-related adverse events for tramadol/APAP were somnolence (6.5%), nausea (4.6%), and constipation (3.3%). Mean tramadol/APAP dose was 4.1 tablets (154 mg tramadol/ 1332 mg APAP). CONCLUSION: Tramadol 37.5 mg/APAP 325 mg combination tablets were effective and safe as add-on therapy with COX-2 NSAID for treatment of OA pain.     

Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis: appropriate trial design considerations and results of a randomized, placebo-controlled trial

OBJECTIVE: To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA). METHODS: In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination). RESULTS: In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was -2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events. CONCLUSION: Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.     

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 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.