Celecoxib versus diclofenac for the treatment of ankylosing spondylitis: 12-week randomized study in Norwegian patients.

OBJECTIVE: To compare the efficacy and safety of two different doses of celecoxib and diclofenac in the treatment of Norwegian patients with ankylosing spondylitis. METHODS: In this 12-week, double-blind, non-inferiority trial patients were randomized to 200 mg once daily (qd) celecoxib, 400 mg qd celecoxib, or 50 mg three times daily (tid) diclofenac. The primary objective compared patients' assessments of Global Pain Intensity, measured on a visual analogue scale. RESULTS: A total of 330 patients were randomized (200 mg celecoxib, n = 107; 400 mg celecoxib, n = 108; diclofenac, n = 115). Least squares mean changes in Global Pain Intensity at 12 weeks were -25.8 mm, -30.6 mm and -28.2 mm, respectively. Both celecoxib treatment groups were non-inferior to diclofenac. More patients in the 400 mg celecoxib group met the Assessments in Ankylosing Spondylitis 20 responder criteria at Week 12 (60.2%) than in the celecoxib 200 mg (51.4%) and the diclofenac 50 mg (57.4%) groups. Adverse events were mild-to-moderate in severity, with dyspepsia and diarrhoea the most commonly reported. CONCLUSIONS: Celecoxib and diclofenac both provided pain reduction, in addition to improvements in disease activity and functional capacity, in patients with ankylosing spondylitis.

Efficacy and safety of nonsteroidal anti-inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo-controlled study.

AIM: To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee. METHOD: Patients of Asian descent with knee OA, aged ≥ 45 years, in a flare state with a functional capacity classification of I-III, received celecoxib 200 mg once daily, naproxen 500 mg twice daily or placebo, for 6 weeks. The change in Patient's Assessment of Arthritis Pain (week 6 vs. baseline) was the primary endpoint. Secondary endpoints, including Patient's and Physician's Global Assessments of Arthritis, Western Ontario and McMaster Universities OA Index (WOMAC), use of complementary and alternative medicines, incidence of treatment-emergent adverse events (TEAEs) and measurements of upper gastrointestinal tolerability, were also assessed. RESULTS: Three hundred and sixty-seven patients were randomized: 145 to celecoxib, 144 to naproxen and 78 to placebo. Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline in visual analogue scale score [standard error] -37.1 [2.0] for celecoxib and -37.5 [2.0] for naproxen). Patient's and Physician's Global Assessment of Arthritis, WOMAC scores, Pain Satisfaction Scale and Patient Health Questionnaire-9 showed statistically significant improvement in active treatment groups versus placebo, with the exception of naproxen WOMAC scores. Treatment-related TEAEs occurred in 19 (13%), 34 (24%) and six (8%) patients in the celecoxib, naproxen and placebo groups, respectively. CONCLUSION: Celecoxib and naproxen were comparable in their effects to reduce the signs and symptoms of knee OA in Asian patients. Celecoxib was shown to be safe and well tolerated in this patient population.

Application of the OMERACT filter to measures of core outcome domains in recent clinical studies of acute gout.

OBJECTIVE: To determine the extent to which instruments that measure core outcome domains in acute gout fulfill the Outcome Measures in Rheumatology (OMERACT) filter requirements of truth, discrimination, and feasibility. METHODS: Patient-level data from 4 randomized controlled trials of agents designed to treat acute gout and 1 observational study of acute gout were analyzed. For each available measure, construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic, and repeated measures generalized estimating equations were assessed. Floor and ceiling effects were also assessed and minimal clinically important difference was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement. RESULTS: There was evidence for construct validity and discriminative ability for 3 measures of pain [0 to 4 Likert, 0 to 10 numeric rating scale (NRS), 0 to 100 mm visual analog scale (VAS)]. Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment. CONCLUSION: There is sufficient evidence to support measures of pain (using Likert, NRS, or VAS), joint tenderness, and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.

Celecoxib and Diclofenac Plus Omeprazole are Similarly Effective in the Treatment of Arthritis in Patients at High GI Risk in the CONDOR Trial.

OBJECTIVE: Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal (GI) risk who were enrolled in the CONDOR (Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) trial. METHODS: CONDOR was a 6-month, prospective, double-blind, triple-dummy, parallel-group, randomized, multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release (SR) 75 mg twice daily plus omeprazole 20 mg daily. Patients were Helicobacter pylori negative, had osteoarthritis (OA) or rheumatoid arthritis (RA), were aged ≥60 years, were with or without a history of gastroduodenal ulceration, or were ≥18 years with previous gastroduodenal ulceration. Patients' Global Assessment of Arthritis was determined at each study visit. RESULTS: A total of 4484 patients were randomized to treatment (2238 celecoxib, 2246 diclofenac SR) and included in the intention-to-treat analyses. Least squares mean (LSM) (standard error [SE]) for Patients' Global Assessment of Arthritis was 3.219 (0.017) and 3.221 (0.017) at baseline for celecoxib and diclofenac SR (p=0.90). Improvement in both groups was similar in months 2, 4, and 6; at month 1 the LSM (SE) was 2.647 (0.017) and 2.586 (0.017) for celecoxib and diclofenac (p=0.0025). LSM difference (SE) from baseline to final visit demonstrated an improvement of 0.75 (0.02) in celecoxib-treated patients and 0.77 (0.02) in diclofenac SR-treated patients (p=0.42). CONCLUSIONS: Celecoxib and diclofenac plus omeprazole were shown to have similar efficacy in patients with OA and/or RA at increased GI risk who were enrolled in the CONDOR trial. TRIAL REGISTRY: Trial was registered under ClinicalTrials.gov identifier NCT00141102.

Efficacy and safety of celecoxib versus diclofenac and omeprazole in elderly arthritis patients: a subgroup analysis of the CONDOR trial.

OBJECTIVE: To compare the safety and efficacy of celecoxib versus diclofenac slow release (SR) plus omeprazole in elderly arthritis patients. RESEARCH DESIGN AND METHODS: Patients aged≥65 years, with osteoarthritis and/or rheumatoid arthritis, at high gastrointestinal (GI) risk who participated in the CONDOR trial (Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) were included in this subanalysis. CONDOR was a 6-month prospective, double-blind, randomized, parallel-group, multicenter, international study comparing treatment with celecoxib 200 mg twice daily (BID) versus diclofenac SR 75 mg BID plus omeprazole 20 mg daily. MAIN OUTCOME MEASURES: The primary end point was a composite of Clinically Significant Upper and Lower GI Events adjudicated by an independent blinded expert committee. Efficacy was determined by the Patient's Global Assessment of Arthritis. RESULTS: A total of 2446 patients aged≥65 years were included in the intent-to-treat (ITT) population (n=1219 celecoxib; n=1227 diclofenac). Eight patients in the celecoxib group and 52 in the diclofenac group were adjudicated as having Clinically Significant Upper and Lower GI events (adjusted odds ratio: 6.27; p<0.0001). Clinically significant reductions in hemoglobin (≥2 g/dL) and/or hematocrit (≥10%) were observed in 23 patients in the celecoxib group and in 76 in the diclofenac group (relative risk: 3.22 [95% confidence interval: 2.04-5.07]; p<0.0001). Incidence of moderate-to-severe abdominal symptoms and discontinuation of treatment due to GI adverse events (AEs) were lower in the celecoxib group. The Patient's Global Assessment of Arthritis score least squares mean change from baseline to final visit and percentage of patients rating treatment efficacy as good/very good at baseline and final visit were similar in both groups. LIMITATIONS: The dose of celecoxib used is consistent with the European label for the management of osteoarthritis and may not reflect what is commonly prescribed in current clinical practice in the United States. The data were obtained in a clinical trial setting where patients were enrolled based on specific inclusion and exclusion criteria; as such, the patients may not be broadly representative of the patient population in a general practice setting. CONCLUSIONS: Efficacy was comparable in the two treatment groups. There were fewer endpoints as well as fewer GI AEs reported in patients treated with celecoxib compared with diclofenac. These data may help physicians in their treatment decisions for elderly patients with arthritis.

Gastrointestinal tolerability of NSAIDs in elderly patients: a pooled analysis of 21 randomized clinical trials with celecoxib and nonselective NSAIDs.

BACKGROUND: Gastrointestinal (GI) tolerability is an important treatment consideration for physicians when choosing a nonselective nonsteroidal anti-inflammatory drug (NSAID) for their elderly arthritis patients. The objective of this study was to compare the GI tolerability of the cyclooxygenase-2 selective NSAID celecoxib and nonselective NSAIDs in elderly patients with arthritis aged 65 years or older. METHODS: This was a retrospective, pooled analysis of patients aged 65 years or older with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) from randomized, parallel-group trials. Selected trials had a duration of ≥2 weeks and at least one celecoxib 200-400 mg/day and one nonselective NSAID (naproxen, ibuprofen, or diclofenac) arm. Patient-level data from the safety populations of the trials were pooled. Analysis included the combined incidence of the GI intolerability adverse events (AEs) (abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea) and incidence and time to trial discontinuation due to these intolerability AEs. RESULTS: A total of 21 trials were selected involving 9461 elderly patients (mean age 71.9 years). Of these, 5872 received celecoxib, 1104 naproxen, 151 ibuprofen, and 2334 diclofenac. The combined incidence of GI intolerability AEs were reported by significantly fewer patients treated with celecoxib (16.7%) than naproxen (29.4%; p < 0.0001), ibuprofen (26.5%; p = 0.0016), or diclofenac (21.0%; p < 0.0001). The discontinuation rate due to GI intolerability AEs was significantly lower for celecoxib (4.0%) versus naproxen (8.1%; p < 0.0001) and ibuprofen (7.3%; p < 0.05), but not diclofenac (4.2%; p = 0.75). CONCLUSIONS: Among elderly arthritis patients, the incidence of GI intolerability AEs was lower with celecoxib than with naproxen, ibuprofen, or diclofenac. Fewer elderly patients discontinued due to GI intolerability AEs with celecoxib than with either naproxen or ibuprofen.