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Background: Previous studies have shown that 20% to 40% of patients requiring nonsteroidal anti-inflammatory drugs (NSAIDs) are concomitantly prescribed gastroprotective agents (GPAs) such as proton pump inhibitors (PPIs) and H2-receptor antagonists., Objective: The purpose of this study was to examine NSAID prescription patterns and the concurrent use of GPAs in a large national sample of patients who were prescribed NSAIDs for the first time., Methods: Patterns of NSAID use, particularly chronic NSAID use, and of concomitant use of GPAs were examined using a large US-based prescription database. Patients with at least 1 NSAID prescription dispensed between May 1 and August 31, 1998, were identified. Persons with any NSAID prescription within 4 months prior to the first (index) prescription were excluded. The remaining patients were defined as new NSAID users and then classified as chronic users (> or = 30 days of supply of NSAIDs during the 120 days of follow-up after the first NSAID prescription) or acute users (<30 days of NSAID supply during the 120 days of follow-up). Concomitant GPA use was defined as receipt of any GPA prescription between the fill date of NSAID prescription and 125% of days of supply. NSAIDs included diclofenac/misoprostol (in a fixed combination), diclofenac, naproxen, nabumetone, ibuprofen, and "other" (comprising several less frequently prescribed agents). Patients were classified as users of a particular NSAID based on the first NSAID prescription they received. GPAs included PPIs, H2-receptor antagonists, and misoprostol., Results: A total of 3,028,808 new NSAID users were identified. Chronic NSAID users (47.8% of the sample) were older than acute users. The percentage of new chronic users aged > or = 65 years for each of the NSAIDs was 41.2% for diclofenac/ misoprostol, 33.0% for nabumetone, 30.8% for diclofenac, 20.4% for naproxen, and 20.3% for ibuprofen. The percentage of women was higher among patients treated with diclofenac/misoprostol than among patients treated with all other NSAIDs (P < 0.001). During the 120 days of follow-up, the percentages of NSAID users with concomitant GPA use were 22.7% for diclofenac/misoprostol, 16.3% for diclofenac, 11.5% for naproxen, 18.0% for nabumetone, 12.3% for ibuprofen, and 14.8% for other NSAIDs. Based on days of supply, the rates of concomitant GPA use were 31.1%, 23.6%, 17.6%, 27.3%, 18.8%, and 22.5% for diclofenac/misoprostol, diclofenac, naproxen, nabumetone, ibuprofen, and other NSAID users, respectively. Among those who were taking GPAs before the NSAID index prescription date, -89% continued GPA therapy., Conclusions: Approximately 22% of the days of NSAID supply were covered by GPAs. Prior GPA use was the strongest predictor of subsequent concomitant GPA/ NSAID use. Differences in GPA use were observed among patients using different NSAIDs.

Nonsteroidal anti-inflammatory drugs. (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response (P = 0.025 and 0.001 vs. placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index (P<0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy (P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA.

This 4-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study was designed to compare the efficacy and safety of etodolac and nabumetone in the treatment of patients with active osteoarthritis (OA) of the knee. Ninety-one patients received etodolac 400 mg twice daily, 89 received nabumetone 1500 mg once daily, and 90 received placebo. Both active treatments significantly improved the patients' condition relative to baseline (P < or = 0.001) at all evaluations during treatment and relative to placebo (P < or = 0.05) by visit 4. Improvement relative to placebo in investigator's global assessments was earlier in the etodolac group (ie, by visit 3) than in the nabumetone group. At visit 4, improvement in investigator's and patient's global assessment scores, and in the distribution of investigator's assessment scores, was significantly (P < or = 0.05) greater in the etodolac group than in the nabumetone group. Other than hypokalemia, which occurred only in three patients in the nabumetone group (P = 0.035), there were no significant differences among the groups in the frequency of study events or premature discontinuation from the study as a result of study events. Study events considered at least possibly treatment related were reported for 26 patients in the etodolac group (28.6%), 20 in the nabumetone group (22.5%), and 23 in the placebo group (25.6%). The most frequently reported symptoms for all groups were dyspepsia, nausea, and headache. Four patients treated with nabumetone (4.5%) had elevations in aspartate aminotransferase or alanine aminotransferase during treatment. The results of this study show that etodolac 400 mg twice daily is at least as effective as nabumetone 1500 mg once daily and is equally well tolerated in the treatment of patients with active OA of the knee; etodolac may have an earlier onset of action and/or a relatively greater efficacy in patient and investigator global assessments than nabumetone.

The neuropeptide substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. In this double-blind randomized study, 70 patients with osteoarthritis (OA) and 31 with rheumatoid arthritis (RA) received capsaicin (a substance P depletor) or placebo for four weeks. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily. Pain relief was assessed using visual analog scales for pain and relief, a categorical pain scale, and physicians' global evaluations. Most of the patients continued to receive concomitant arthritis medications. Significantly more relief of pain was reported by the capsaicin-treated patients than the placebo patients throughout the study; after four weeks of capsaicin treatment, RA and OA patients demonstrated mean reductions in pain of 57% and 33%, respectively. These reductions in pain were statistically significant compared with those reported with placebo (P = 0.003 and P = 0.033, respectively). According to the global evaluations, 80% of the capsaicin-treated patients experienced a reduction in pain after two weeks of treatment. Transient burning was felt at the sites of drug application by 23 of the 52 capsaicin-treated patients; two patients withdrew from treatment because of this side effect. It is concluded that capsaicin cream is a safe and effective treatment for arthritis.