OBJECTIVE:In spite of numerous studies demonstrating the serious gastrointestinal (GI) toxicity associated with non-selective non-steroidal anti-inflammatory drugs (NSAIDs), many patients at high GI risk continue to receive prescriptions for these drugs, often without gastroprotective agents. Etoricoxib, a COX-2 specific inhibitor, was developed to provide similar efficacy and less GI toxicity than non-selective NSAIDs. We compared the incidence of upper GI Perforations, symptomatic gastroduodenal Ulcers, and upper GI Bleeding (PUBs) in a combined analysis of all randomized, double-blind, clinical trials of chronic treatment with etoricoxib versus NSAIDs completed by June 2003.RESEARCH DESIGN AND METHODS:Data for 5441 individual subjects with osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis were pooled from all 10 multinational etoricoxib trials completed by June 2003. Information on suspected PUBs was prospectively collected in all protocols, and all investigator-reported PUBs were judged by a blinded, external adjudication committee using pre-specified criteria. PUBs were analyzed using COX proportional hazards models using terms for treatment and known PUB risk factors.MAIN OUTCOME MEASURE:The incidence of confirmed PUBs among patients treated with etoricoxib 60 mg, 90 mg, or 120 mg (combined N=3226) was compared to that among patients treated with ibuprofen, diclofenac, or naproxen (combined N=2215).RESULTS:The incidence of PUBs over 44.3 months was significantly lower with etoricoxib vs. NSAIDs [cumulative incidence 1.24% vs. 2.48%, p < 0.001; rate/100 patient-years 1.00 vs. 2.47; relative risk 0.48, 95% Confidence Interval (CI) 0.32, 0.73]. Results of analysis of events occurring during the first year of treatment and subgroup analyses were consistent with the primary result.CONCLUSIONS:Treatment with etoricoxib was associated with a significantly lower incidence of PUBs than was treatment with non-selective NSAIDs. The difference was consistent in subgroups of patients defined by a variety of known risk factors.

BACKGROUND The magnitude and duration of the benefit of running and other aerobic exercise on disability and mortality in elderly persons are not well understood. We sought to quantify the benefits of aerobic exercise, including running, on disability and mortality in elderly persons and to examine whether morbidity can be compressed into later years of life by regular exercise. METHODS A 13-year prospective cohort study of 370 members of a runners' club for persons aged 50 and older and 249 control subjects initially aged 50 to 72 years (mean, 59 years), with annual ascertainment of the Health Assessment Questionnaire disability score, noting any deaths and their causes. Linear mixed models were used to compute postponement in disability, and survival analysis was conducted to determine the time to and causes of death. RESULTS Significantly (P<.001) lower disability levels in runners' club members vs controls and in ever runners vs never runners were sustained for at least 13 years. Reaching a Health Assessment Questionnaire disability level of 0.075 was postponed by 8.7 (95% confidence interval [CI], 5.5-13.7) years in runners' club members vs controls. Running club membership and participation in other aerobic exercise protected against mortality (rate ratio, 0.36 [95% CI, 0.20-0.65] and 0.88 [95% CI, 0.77-0.99], respectively), while male sex and smoking were detrimental (rate ratio, 2.4 [95% CI, 1.4-4.2] and 2.2 [95% CI, 1.1-4.6], respectively). Controls had a 3.3 times higher rate of death than runners' club members, with higher death rates in every disease category. Accelerated rates of disability and mortality were still not seen in the runners' club members; true compression of morbidity was not yet observable through an average age of 72 years. CONCLUSION Running and other aerobic exercise in elderly persons protect against disability and early mortality, and are associated with prolongation of a disability-free life.

OBJECTIVE To estimate the morbidity, mortality, and lifetime costs of care for rheumatoid arthritis (RA). METHODS We developed a Markov model based on the Arthritis, Rheumatism, and Aging Medical Information System Post-Marketing Surveillance Program cohort, involving 4,258 consecutively enrolled RA patients who were followed up for 17,085 patient-years. Markov states of health were based on drug treatment and Health Assessment Questionnaire scores. Costs were based on resource utilization, and utilities were based on visual analog scale-based general health scores. RESULTS The cohort had a mean age of 57 years, 76.4% were women, and the mean duration of disease was 11.8 years. Compared with a life expectancy of 22.0 years for the general population, this cohort had a life expectancy of 18.6 years and 11.3 quality-adjusted life years. Lifetime direct medical care costs were estimated to be $93,296. Higher costs were associated with higher disability scores. CONCLUSION A Markov model can be used to estimate lifelong morbidity, mortality, and costs associated with RA, providing a context in which to consider the potential value of new therapies for the disease.

Gastrointestinal (GI) co-therapy, procedures, and hospitalizations in a GI outcomes study of rofecoxib vs. naproxen in rheumatoid arthritis