Co-prescribing of proton pump inhibitors among chronic users of NSAIDs in the UK.

OBJECTIVES: Co-prescribing of proton pump inhibitors (PPIs) with non-selective NSAIDs (nsNSAIDs) is recommended in patients at risk of gastrointestinal (GI) events. This study estimated usage of PPI co-therapy among chronic nsNSAID users and determined factors associated with concurrent nsNSAID-PPI use. METHODS: The retrospective study was based on the Intercontinental Marketing Services (IMS) Health UK MediPlus database and included subjects > or = 40 yrs of age who received their first oral nsNSAID prescription between July and December 2002 and who had > or = 60 days of nsNSAID supply during the following year. Days with nsNSAID-PPI overlap were calculated and logistic regression was used to identify factors associated with nsNSAID-PPI overlap. A generalized linear model was used to assess the degree of association of GI risk factors with the nsNSAID-PPI overlap ratio among PPI users. RESULTS: Of 16,344 patients included, 1586 received at least one PPI prescription. Among PPI users, PPIs were available on approximately 50% of the days with nsNSAID therapy. After multivariate adjustment, age > or = 65 yrs, history of any hospitalization and co-prescriptions for anti-coagulants or oral corticosteroids increased the odds of any nsNSAID-PPI overlap by 21-68%. Prior gastroprotective agent (GPA) use increased the odds of any PPI use during follow-up 16-fold and nsNSAID-PPI overlap 19-fold. Among PPI users, patients with prior use of any GPA had a 2.46 times higher nsNSAID-PPI overlap ratio. CONCLUSIONS: PPI utilization correlates poorly with nsNSAID use in the UK. GI safety of nsNSAID-PPI co-therapy observed in controlled trials may therefore not be achieved in clinical practice.

Therapy switching and associated costs in elderly patients receiving COX-2 selective inhibitors or non-selective non-steroidal anti-inflammatory drugs in Quebec, Canada.

OBJECTIVES: Lack of efficacy or tolerability of some non-steroidal anti-inflammatory drugs (NSAIDs) may lead to switching between non-selective NSAIDs (nsNSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors (coxibs), potentially increasing treatment costs due to additional physician visits and wastage of medication. This study assessed drug switching and associated costs among elderly chronic NSAID users. METHODS: Data for patients who filled their first prescription for a coxib or nsNSAID in 2001 were obtained from the Quebec Health Insurance Agency. Follow-up was terminated at the earliest of: 1 yr, the first day without NSAID exposure following the index filling date, or death. Patients could switch NSAIDs several times during follow-up. Person-days of exposure were categorized by the NSAID most recently dispensed: rofecoxib, celecoxib, Arthrotec(R) or non-Arthrotec (nA) nsNSAID. Cox regression models compared time to switch between groups, adjusting for patient baseline characteristics. Upon a switch, pills remaining from the previous prescription were considered wasted. The costs of wasted pills and switch-associated physician visits were estimated. RESULTS: Throughout follow-up, patients filled 38 267 prescriptions for rofecoxib, 31 282 for celecoxib, 1108 for Arthrotec and 4388 for nA-nsNSAIDs. Adjusted hazard ratios (95% confidence interval) for switching versus nA-nsNSAIDs were: rofecoxib, 0.39 (0.35-0.44); celecoxib, 0.43 (0.38-0.48). Compared with nA-nsNSAID prescriptions, adjusted switching-related healthcare costs were 53 and 47% lower on average for rofecoxib and celecoxib prescriptions, respectively. These costs were 34% higher for Arthrotec prescriptions than for nA-nsNSAIDs. CONCLUSIONS: Compared with recipients of nsNSAIDs, coxib recipients were less likely to switch medications and had approximately half the adjusted costs for switching-related wasted resources per prescription.

Association between health-related quality of life and clinical efficacy endpoints in rheumatoid arthritis patients after four weeks treatment with anti-inflammatory agents.

BACKGROUND: Improvement of health-related quality of life (QoL) is increasingly recognized as a maj or treatment goal for patients with rheumatoid arthritis (RA). There are several measures of general health status and of physical functioning for assessing treatment effects on QoL in patients with RA, however, the relationship between QoL outcomes and conventional clinical efficacy endpoints is not completely understood. OBJECTIVE: To describe the association between changes in QoL and changes in other efficacy measures, among patients with RA after four weeks of treatment with etoricoxib, naproxen or placebo, and to explore differences in the association of changes in efficacy and changes in QoL parameters across treatment groups. METHODS: The study used data from 1684 patients with RA enrolled in two identical clinical trials (one US and one multinational). Patients were randomized to placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily in a 2 : 2: 1 allocation ratio. Primary efficacy endpoints were tender joint count, swollen joint count, patient global assessment of disease activity (100 mm VAS), and investigator global assessment of disease activity (0 - 4 Likert scale). QoL assessments were based on the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Survey Short Form 36 (SF-36). Mean differences between baseline and week four were calculated for each parameter studied. Linear regression analysis was performed to assess the association between changes in clinical efficacy and changes in QoL parameters, adjusted for covariates. RESULTS: The degree of association between changes in tender or swollen joint counts and changes in QoL variables was low, explaining less than 10% of the variability for most QoL variables, except bodily pain (SF-36). In contrast, changes in patient global assessment of disease activity explained 33% of the variability in the overall HAQ score, and in the physical component score (SF-36; adjusted regression models). Values for investigator global assessment of disease activity were below those for patient global assessment but above joint count measures. Results were similar between the etoricoxib, naproxen and placebo groups in the degree of association between changes in efficacy and QoL variables. CONCLUSION: Currently used efficacy endpoints are less than ideal predictors of change in QoL. There is no evidence from this study that the association between changes in CE endpoints and QoL was different across treatments. Our results highlight the need to assess both conventional efficacy measures and QoL in clinical trials of RA treatments.

Economic evaluation of celecoxib, a new cyclo-oxygenase 2 specific inhibitor, in Switzerland.

OBJECTIVE: The aim of this study was to predict the cost effectiveness of celecoxib, a cyclo-oxygenase 2 (COX-2) specific inhibitor, in the treatment of arthritis patients in Switzerland. METHODS: We applied a decision analytical model to compare the effects of 6 months' treatment with the following: (i) celecoxib; (ii) nonsteroidal anti-inflammatory drug (NSAID) alone; NSAID protected with (iii) proton pump inhibitor (PPI), (iv) histamine H2 receptor antagonist (H2RA), or (v) misoprostol; and (vi) diclofenac/misoprostol. Treatment costs included drug acquisition and the management of gastrointestinal (GI) adverse effects, classified as GI discomfort, symptomatic ulcer, anaemia and serious GI events (requiring hospitalisation). Probabilities were derived from celecoxib clinical trials and the literature. Drug utilisation patterns and treatment costs reflecting Swiss practice were obtained from local sources. Analysis was from the public health insurers' perspective. A range of sensitivity analyses was performed. RESULTS: For the base case of patients at typical risk (0.56% per 6 months) of serious GI events, the total expected costs of 6 months' treatment were as follows: celecoxib 435 Swiss francs (SwF); NSAID alone SwF510; diclofenac/misoprostol SwF522; and other protected NSAID regimens between SwF1034 and SwF1415. Celecoxib remained the lowest costing treatment over all categories of GI risk. Celecoxib generated 115 expected adverse events per 1000 patients per 6 months, followed by NSAID + PPI (119), NSAID + H2RA (154), NSAID + misoprostol (202), diclofenac/misoprostol (203), and NSAID alone (220), again for the base case. The cost per adverse event averted for celecoxib compared with NSAIDs alone was estimated in a stochastic version of the model using Monte Carlo simulation. In 95% of 500 iterations, celecoxib was predicted to save both costs and adverse events, thus dominating NSAIDs alone; the maximum cost per adverse event averted was SwF440. CONCLUSIONS: Celecoxib is predicted to be the most cost effective of the treatments considered for managing arthritis patients in Switzerland. A policy of switching patients from NSAIDs to celecoxib is predicted to be cost saving for public health insurers, while reducing the burden of iatrogenic GI side effects. Greater cost savings would be realised when patients are switched from NSAIDs used with gastroprotective agents. Models such as this can provide a useful but simplified view of treatment outcomes and predicted results require prospective validation in clinical practice.

The burden of arthritis and nonsteroidal anti-inflammatory treatment. A European literature review.

The purpose of this literature review is to summarise data available from publications describing the burden of osteoarthritis and rheumatoid arthritis in Europe, and to highlight gaps in the literature. On the basis of extensive literature research, the epidemiology of arthritis, its treatment costs, and iatrogenic costs related to nonsteroidal anti-inflammatory drug (NSAID) treatments are described, differentiating results by country. The review shows that, as well as having a significant impact on healthcare budgets, arthritis also affects patients and caregivers. For those countries where data were available, indirect costs were found to be of comparable magnitude to direct costs. Additionally, it was found that the iatrogenic costs related to the treatment of NSAID-induced adverse events are a significant component of the total costs of arthritis. The number of publications on the burden of arthritis in Europe is rather small in comparison with what is available for the US. Comparison of national results shows wide variations between countries, which may be partly due to discrepancies in the methodology applied to estimate the burden of arthritis, the cost items included in the analysis, and the data sources used to gather cost information. Additionally, comparing the burden of arthritis by country across Europe is difficult because of the variety of ways in which results are presented, e.g. on a per-patient basis, or for the whole population. To better understand the burden of illness of arthritis in Europe, not only is more research required, but the methodology to be applied in burden-of-illness analyses must also be standardised.

[Cost-effectiveness analysis: radioiodine or antithyroid medication in primary treatment of immune hyperthyroidism]. / Kosten-Effektivitäts-Analyse: Radioiod oder thyreostatische Medikation bei der Primärbehandlung der Immunhyperthyreose.

AIM: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. METHOD: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq 1-131 residual activity. RESULT: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. CONCLUSION: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake).

[Costs of coronary heart diseases over the remaining life time in coronary heart disease cases--an analysis of the current status of coronary heart disease cases in Germany from the social perspective]. / Kosten koronarer Herzkrankheiten über die verbleibende Lebenszeit von KHK-Fällen--Eine Analyse des aktuellen Bestandes an KHK-Fällen in Deutschland aus gesellschaftlicher Perspektive.

UNLABELLED: Cardiovascular diseases are the major cause of death not only in Germany. Coronary heart diseases result in substantial disability and loss of productivity and contribute to escalating costs of health care. OBJECTIVE: It was our objective to estimate the costs of CHD for the German population from the perspective of the society. The characteristic of this approach is the calculating of costs until the approximated end of life. METHODS: In the study, all health care costs concerning CHD in Germany were allocated to age, sex, health care sector and primary diagnosis on the basis of comprehensive data on morbidity, mortality, direct and indirect costs. For the estimate of indirect costs the human capital approach was taken. Considered as cases were all patients hospitalized in the reference year (1996). The costs of this cohort in 1996 and up to their protected end of life were estimated. It was taken into account that, in comparison to the general population, life expectancy of cases with risk factors or CHD would have been reduced. In calculating indirect costs, gender and age specific unemployment rates were considered. All future costs were discounted by 4% from the reference year onward. RESULTS: Direct costs are approximately 39 billion DM discounted at 4%, indirect costs total 73 billion DM. The average cost per case (including morbidity and mortality) until the approximated end of life is nearly 125,000 DM. CONCLUSION: In our cost analysis, the indirect costs are higher than the direct costs. For the future, it will be important to estimate the costs of prevalent cases until the end of life and to compare the influence of different interventions on these parameters and on the whole budget of the social security system.