Margaret Noyes Essex

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

Abstract 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.

Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials

Objective: Further understand the safety profile of celecoxib and provide safety information for important adverse events (AEs). Methods: Analysis of randomized controlled trials from the Pfizer clinical trial repository (final study reports completed by 31 July 2011) in which celecoxib was compared with placebo or non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) for treatment of pain or inflammation in adults. Safety end points comprised 18 terms that had been identified as important AEs among all NSAIDs. Results: There was a greater risk of edema (risk difference (95% confidence interval) 0.77% (0.45, 1.09)); hypertension (0.28% (-0.01, 0.57)); angioedema (0.16% (-0.06, 0.39) and allergic reactions (0.15% (-0.10, 0.40)) with celecoxib than with placebo, while a greater risk of gastrointestinal (GI) hemorrhage (-0.15% (-0.47, 0.16)) was seen with placebo. There was a greater risk of GI hemorrhage (-0.53% (-0.72, -0.33)), GI ulceration (-0.46% (-0.60, -0.33)), edema (-0.62% (-0.89, -0.35)) and hypertension (-0.57% (-0.82, -0.33)) with nsNSAIDs than with celecoxib. Conclusions: The magnitude of risks associated with NSAIDs is small and similar in celecoxib-, nsNSAID- and placebo-treated patients. This analysis provides safety information that will allow physicians to make informed treatment decisions for patients who are appropriate candidates for celecoxib use.

Efficacy and Tolerability of Celecoxib versus Naproxen in Patients with Osteoarthritis of the Knee: A Randomized, Double-Blind, Double-Dummy Trial

OBJECTIVE: To assess the efficacy and tolerability of celecoxib versus naproxen in patients with osteoarthritis (OA) of the knee. METHODS: This 6-month, randomized, double-blind, double-dummy trial was conducted at 47 centres in the USA. Patients with OA of the knee were randomized to receive 200 mg celecoxib orally once daily or 500 mg naproxen orally twice daily. The primary endpoint was defined as a 20% improvement from baseline to 6 months in Western Ontario and McMaster Universities (WOMAC) OA total score. RESULTS: A total of 586 out of 589 randomized patients received at least one dose of celecoxib (n = 294) or naproxen (n = 292). The primary endpoint (6-month response rate) was achieved by 52.7% and 49.7% of patients in the celecoxib and naproxen treatment groups, respectively. Significantly fewer discontinuations due to gastrointestinal adverse events occurred in patients receiving celecoxib than in those receiving naproxen (4.1% versus 15.1%, respectively). CONCLUSIONS: Over the 6-month study period, celecoxib provided similar improvements in OA symptoms to naproxen. In addition, celecoxib provided better upper gastrointestinal tolerability than naproxen.

Response to Nonsteroidal Anti-Inflammatory Drugs in African Americans with Osteoarthritis of the Knee

Objective: This 6-week, randomized, double-blind, parallel-group study compared the analgesic efficacy, tolerability and safety of celecoxib, naproxen and placebo in African Americans with osteoarthritis (OA) of the knee. Methods: A total of 322 patients aged ≥ 45 years with OA of the knee in a flare state received 200 mg celecoxib orally once daily, 500 mg naproxen orally twice daily or placebo for 6 weeks. The primary endpoint was change from baseline in the Patients Assessment of Arthritis Pain. Results: Celecoxib was as effective as naproxen in reducing OA pain. Similar efficacy was observed in many of the secondary outcome measures. Celecoxib was well tolerated and demonstrated favorable upper gastro-intestinal tolerability. Improvements in outcome measures were numerically greater in the active treatment groups compared with the placebo group, but did not reach statistical significance. Conclusions: Celecoxib was as effective as naproxen in relieving OA pain in African Americans and was well tolerated. Few significant differences were observed between active treatments and placebo, possibly because of a strong placebo effect.

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

Abstract 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.

Efficacy and tolerability of celecoxib and naproxen versus placebo in Hispanic patients with knee osteoarthritis

Background Celecoxib is an effective treatment for osteoarthritis (OA). However, information on its efficacy and safety profile in different racial/ethnic groups is limited. Noticeable differences among racial groups are found in other disease states, but a thorough investigation of OA is lacking. The objective of this study was to determine if celecoxib 200 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of OA of the knee in Hispanic patients. Methods Hispanic patients aged ≥45 years with knee OA were randomized to receive celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo for 6 weeks. The primary efficacy variable was the change in Patient’s Assessment of Arthritis Pain at 6 weeks compared with baseline. Secondary variables were change in Patient’s and Physician’s Global Assessments of Arthritis from baseline to week 6/early termination, change in Western Ontario and McMaster Universities OA Index (WOMAC) from baseline to week 6/early termination, change in American Pain Society pain score, Pain Satisfaction Scale, Patient Health Questionnaire (PHQ-9), and measurements of upper gastrointestinal tolerability. Results In total, 239 patients completed the trial (96 celecoxib, 96 naproxen, 47 placebo). Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline [standard error] −39.7 [2.7] for celecoxib and −36.9 [2.6] for naproxen). Patient’s and Physician’s Global Assessments of Arthritis, WOMAC scores, upper gastrointestinal tolerability, Pain Satisfaction Scale, and PHQ-9 showed no statistically significant differences between the celecoxib and naproxen groups. The incidence of adverse events and treatment-related adverse events were similar among the treatment groups. Conclusion Celecoxib 200 mg once daily was as effective as naproxen 500 mg twice daily in the treatment of signs and symptoms of knee OA in Hispanic patients. Celecoxib was shown to be safe and well tolerated in this patient population.

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

To compare the efficacy, tolerability and safety of celecoxib, naproxen and placebo in Asian patients with osteoarthritis (OA) of the knee.

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.

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.

Children's International Polyposis (CHIP) study : a randomized, double-blind, placebo-controlled study of celecoxib in children with familial adenomatous polyposis

Objective To evaluate the efficacy and safety of celecoxib versus placebo in the prevention and treatment of colorectal polyposis in children with familial adenomatous polyposis (FAP). Methods In this Phase III, double-blind, randomized, placebo-controlled, multicenter trial patients aged 10–17 years with FAP were randomized to celecoxib (16 mg/kg/day) or placebo for up to 5 years. Patients underwent annual assessments, including colonoscopies, to detect the time from randomization to the earliest occurrence of ≥20 polyps (>2 mm in size) or colorectal malignancy. The study was terminated early due to low rate of observed endpoints combined with a lower than expected enrollment rate. Descriptive results are provided. Results Of 106 randomized patients, 55 were treated with celecoxib (mean age 12.6 years; 52.7% female) and 51 were given placebo (mean age 12.2 years; 54.9% female). Disease progression (≥20 polyps, >2 mm in size) was observed in seven (12.7%) and 13 (25.5%) patients, respectively. The median time to disease progression was 2.1 years in the celecoxib group and 1.1 years for placebo. No patient developed colorectal cancer. The rate of adverse events (AEs) was similar in both groups (75.5% and 72.9%, respectively). Three patients in the celecoxib group (none in the placebo group) experienced serious AEs. Conclusion In children with FAP, celecoxib was a well-tolerated treatment that was associated with a lower rate of colorectal polyposis and a longer time to disease progression compared with placebo. Due to the low rate of observed endpoints, the long-term impact of these results could not be ascertained.