The number of nonsteroidal antiinflammatory drugs (NSAID's) available for use in the United States has tripled since they were last reviewed here in 1974.1 Although there are several uses for these...

Drug therapy: nonsteroidal antiinflammatory drugs (first of two parts).

Synopsis: Naproxen1 is a propionic acid derivative with analgesic and anti-inflammatory activity which has been widely used in the treatment of rheumatic diseases. Naproxen has been well studied in rheumatoid arthritis and is as effective as aspirin but better tolerated, thus enabling more patients to continue with treatment. For this reason some clinicians now prefer to try propionic acid derivatives, such as naproxen, before aspirin in arthritic patients. In comparative studies with other non-steroidal anti-inflammatory drugs, such as indomethacin, ibuprofen, fenoprofen and others, all drugs were usually of similar overall efficacy although naproxen was sometimes preferred: but as with other non-steroidal anti-inflammatory agents, not all patients will respond to naproxen and in such cases other agents should also be tried until the most satisfactory drug is found for each patient.

Naproxen up to Date: A Review of its Pharmacological Properties and Therapeutic Efficacy and Use in Rheumatic Diseases and Pain States

Newer nonsteroidal antiinflammatory, agents (NSAIs) such as ibuprofen, naproxen, fenoprofen, and tolmetin have broadened the therapeutic choice and increased the chances of providing optimum arthritis control, but require careful assessment of the possibilities for unwanted drug effects when long-term therapy is required. A review of the literature on the gastrointestinal effects of the promising newer NSAIs, as compared with the older agents, aspirin, indomethacin, and phenylbutazone, is presented, highlighting animal toxicology and human adverse reaction surveillance data and the evidence for various suggested pathophysiological mechanisms.

A review of upper-gastrointestinal effects of the newer nonsteroidal antiinflammatory agents.

Objective Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs. Methods We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (>17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size >or=50); and 103 observational studies. Results The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies. Conclusions Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.11192

Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs

Nonsteroidal antiinflammatory drugs (second of two parts).

One hundred nineteen adults with active definite or classical rheumatoid arthritis were studied in a multicenter double-blind crossover study of naproxen (500 mg/day) and aspirin (3.6 Gm/day). Each drug was given in sequence for a six-week study period. Patients already receiving corticosteriod and/or gold therapy were maintained at constant dose throughout the study, but analgesics and other nonsteroidal antiinflammatory agents were discontinued at baseline. Objective and subjective evaluations by both investigator and patient were carried out at two-week intervals. No significant difference in global evaluation of efficacy or individual measures of efficacy was observed between aspirin and naproxen therapy, although physicians' global evaluation tended to favor naproxen. Sedimentation rate was lower on aspirin (naproxen 43.1 mm/hr; aspirin 38.7 mm/hr; P=0.02). Naproxen, 250 mg twice daily, was significantly better tolerated than aspirin, 900 mg four times daily. Mild, moderate, and severe side effects were less frequent with naproxen. The incidence of heartburn was significantly lower on naproxen, and significantly fewer patients terminated their six-week study period on naproxen than on aspirin. There were no significant deviations from baseline values in hematocrit, white cell or differential counts, or in tests of renal and hepatic function during the course of the study.

Naproxen and Aspirin in Rheumatoid Arthritis: A Multicenter Double‐Blind Crossover Comparison Study

This paper presents the results of a multi-center double-blind crossover study of naproxen and aspirin in 119 adult patients (mean age 52) with rheumatoid arthritis. All patients had definite or classical rheumatoid arthritis (ARA criteria) and fulfilled specific criteria for active disease. Non-steroidal anti-inflammatory medication and analgesics were discontinued at onset of the study and replaced randomly by either naproxen (500 mg/day) or aspirin (3.6 g/day). Each drug was then given in sequence for a six week study period. Patients already receiving corticosteroid and/or gold therapy were maintained at constant dose throughout the study. Evaluations were carried out at two week intervals and included questioning of patients for side-effects, investigator and patient global evaluation of drug efficacy and tolerance and measurements of grip strength, walking time, number of clinically active joints, duration of morning stiffness and time to fatigue. Laboratory parameters were closely monitored during ...

D. Odone

Papers

Naproxen and Aspirin in Rheumatoid Arthritis: A Multicenter Double‐Blind Crossover Comparison Study

A multi-center double-blind crossover comparison study of naproxen and aspirin in patients with rheumatoid arthritis.