Dataset Information

Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

ABSTRACT: To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/noncase study was performed among individual case safety reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while noncases were ICSRs without HSRs. NSAIDs were categorized into (i) NSAIDs with high COX-2 selectivity (coxibs), (ii) noncoxib NSAIDs with COX-2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified 13 229 cases and 106 444 noncases. In the first 5 years after marketing, poor-selectivity NSAIDs and acetic acid derivatives were associated with the highest ROR of HSRs (age- and sex-adjusted ROR 2.12, 95% CI 1.98-2.28; and ROR 2.21, 95% CI 1.83-2.66, respectively) compared with coxibs, and sulfonamide NSAIDs were associated with the highest ROR of HSRs compared with nonsulfonamide NSAIDs (age- and sex-adjusted ROR 1.38, 95% CI 1.29-1.47). After the first 5 years of marketing, most of the RORs returned to approximately 1.

SUBMITTER: Bakhriansyah M

PROVIDER: S-EPMC6850345 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

Bakhriansyah Mohammad M Meyboom Ronald H B RHB Souverein Patrick C PC de Boer Anthonius A Klungel Olaf H OH

Fundamental & clinical pharmacology 20190422 5

To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/nonc ...[more]

PMID: 30860620

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Project description:BackgroundDifferences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor (coxib) are affected by drug, dose, duration, outcome definition, and patient gastrointestinal and cardiovascular risk factors. We calculated the absolute risk for each effect.MethodsWe sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal (complicated upper gastrointestinal perforations, ulcers, or bleeds, but not symptomatic or endoscopic ulcers) and serious cardiovascular outcomes (antiplatelet trial collaborators - APTC - outcome of fatal or nonfatal myocardial infarction or stroke, or vascular death).ResultsMeta-analyses and large randomised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data. In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure. Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs; serious cardiovascular events occurred at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events. In the overall comparison, for every 1000 patients treated for a year with coxib rather than NSAID, there would be eight fewer complicated upper gastrointestinal events, but one more fatal or nonfatal heart attack or stroke. Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons. For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications, and two fewer fatal or nonfatal heart attacks or strokes. For rofecoxib there would be six fewer upper gastrointestinal complications, but three more fatal or nonfatal heart attacks or strokes. For lumiracoxib there would be eight fewer upper gastrointestinal complications, but one more fatal or nonfatal heart attack or stroke.ConclusionCalculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs, serious cardiovascular events occur at approximately equal rates. For each coxib, the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events.

Project description:IntroductionIn the treatment of the individual patient, a vision is to achieve the best possible balance between benefit and harm. Such tailored therapy relies upon the identification and characterisation of risk factors for adverse drug reactions. Information relevant to risk factor considerations can be captured in adverse event reports and could be utilised in statistical signal detection.ObjectiveThe aim of this study was to explore whether statistical screening of a broad range of risk factors within a global database of adverse event reports could uncover signals of risk groups for adverse drug reactions.MethodsSubgroup disproportionality analysis was applied to 15.4 million reports entered in VigiBase, the World Health Organization (WHO) global database of individual case safety reports, up to August 2017. Disproportionality analyses for drug-adverse event pairs were performed (1) in the full database and (2) across a range of subgroups defined by the following covariates: patient age, sex, body mass index, pregnancy, underlying condition, reporting country, and geographical region. Drug-adverse event pairs disproportionately over-reported in such subgroups, but not in the full database, and with a substantial difference between the two observed-to-expected ratios, were highlighted as statistical signals. These were further prioritised, through filtering and sorting, for clinical assessment, whereafter clinically relevant signals were communicated to the pharmacovigilance community and the public.ResultsAssessments were performed for 354 prioritised statistical signals, resulting in seven communicated signals describing previously unrecognised potential risk groups related to age (elderly), sex (male and female), body mass index (underweight and obese), and geographical region (Asia), all except one for already established adverse drug reactions. Important aspects considered in the assessments included an evaluation of the disproportionate over-reporting in the subgroup by reviewing alternative explanations and reporting patterns for similar drugs/adverse events/subgroups, and a search for plausible mechanisms to support the risk hypothesis.ConclusionsThis study reveals that it is possible to uncover signals of risk groups for adverse drug reactions through incorporation of broad risk factor screening into statistical signal detection in a global database of adverse event reports. Our findings suggest the potential to use such statistical methodologies for risk characterisation in subpopulations of concern.

Project description:IntroductionFaecal blood loss has been measured using autologous erythrocytes labelled with radioactive chromium for several decades, using generally similar methods. We conducted a systematic review of studies employing this technology to determine the degree of blood loss associated with use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 selective inhibitors (coxibs).MethodsA systematic search of PubMed and the Cochrane Library (to December 2006) was conducted to identify randomized trials in which treatment with aspirin, NSAIDs, or coxibs was continued for at least 7 days, and with at least 7 days of washout for crossover trials. Rates of faecal blood loss associated with these agents were determined in the randomized trials identified. Comparators were placebo, active, or no treatment. Outcomes of interest were mean daily faecal blood loss, and the number or proportion of individuals recording faecal blood above 5 ml/day and above 10 ml/day.ResultsForty-five reports of 47 trials were included, including 1,162 individuals, mostly healthy volunteers and predominantly young men. Only 136 patients (as opposed to healthy volunteers; 12%) were included, and these were mostly older people with an arthritic condition. Most NSAIDs and low-dose (325 mg) aspirin resulted in a small average increase in faecal blood loss of 1 to 2 ml/day from about 0.5 ml/day at baseline. Aspirin at full anti-inflammatory doses resulted in much higher average levels of blood loss of about 5 ml/day. Some individuals lost much more blood than average, at least for some of the time, with 5% of those taking NSAIDs having daily blood loss of 5 ml or more and 1% having daily blood loss of 10 ml or more; rates of daily blood loss of 5 ml/day or 10 ml/day were 31% and 10%, respectively, for aspirin at daily doses of 1,800 mg or greater.ConclusionAt baseline, or with placebo, faecal blood loss is measured at 1 ml/day or below. With low-dose aspirin and some NSAIDs, average values may be two to four times this, and anti-inflammatory doses of aspirin result in much higher average losses. A small proportion of individuals respond to aspirin or NSAIDs with much higher faecal blood loss of above 5 ml/day or 10 ml/day. There are significant limitations regarding the quality and validity of reporting of these studies, such as limited size and inclusion of inappropriate participants. The potential for blood loss and consequent anaemia requires more study.

Dataset Information

Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

Publications

Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase.

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