Incidence and risk estimate of drug‐induced agranulocytosis in Hong Kong Chinese. A population‐based case–control study

Abstract

Purpose Drug‐induced agranulocytosis is a rare but life‐threatening adverse drug reaction. Its epidemiology in Chinese is largely unknown. This study aimed to estimate the incidence, mortality, and risk of the drugs associated with agranulocytosis in Hong Kong Chinese. Methods A population‐based case–control study was conducted using the Clinical Data Analysis and Reporting System, a database managed by the Hong Kong Hospital Authority. Patients with drug‐induced agranulocytosis from 1 January 2004 to 31 December 2013 were identified. World Health Organization causality assessment was used to evaluate the possible drug aetiology of each case. Odd ratios (ORs) of the drug exposure were calculated using exact conditional logistic regression. Results A total of 155 cases of drug‐induced agranulocytosis were identified. Mean age was 51.4 years, and 95 cases were female. Incidence rate was estimated to be 2.2 cases per million person‐years, and the all‐cause mortality of patients with drug‐induced agranulocytosis was 3.9%. Among the cases, the most common associated drug groups were antithyroid drugs (41.9%), antimicrobials (20%), anticonvulsants (10.3%), and antipsychotics (6.5%). Carbimazole had the highest risk of agranulocytosis (adjusted OR 416.7, 95% confidence interval (CI) 51.5–3372.9) with an incidence of 9.2 (95%CI 6.9–12.1) per 10 000 users and 3.6 (95%CI 2.7–4.8) per 10 000 user‐years. Other drugs with significant risk included cephalosporins, clozapine, penicillins, phenytoin, and propyl thiouracil. Conclusions The incidence and mortality in Hong Kong Chinese were relatively low compared to Caucasians. Antithyroid drugs were the most common implicated drug class, and carbimazole had the highest risk of agranulocytosis. Copyright © 2017 John Wiley & Sons, Ltd.

Challenges in diagnosis and management of neutropenia upon exposure to immune-checkpoint inhibitors: meta-analysis of a rare immune-related adverse side effect

“…Data for increased IDR in patients who received ICI are not available, but patients are possibly at a higher risk for IDR when their ability to immune tolerance is altered [46]. Drug-induced agranulocytosis seems to occur in 95% of the cases within the first 60 days of treatment [47]. Adapted to our second case, ICI and not metamizole-mediated neutropenia seems to be more probable, because of the timepoint of occurrence (between the third and fourth ICI therapy cycle) and because metamizole was taken continuously in maximal doses for a long period of time, namely 87 days.…”

Hematopoiesis and the bacterial microbiome

“…Cytopenias, including neutropenia, anemia, thrombocytopenia, and pancytopenia, have been reported for a wide range of antibiotics. [30][31][32][33][34][35] For example, a retrospective analysis found that 5% to 15% of patients developed neutropenia (defined as ,1000 neutrophils per cubic millimeter) after 10 or more days of b-lactam antibiotic treatment. 36 Of the patients that developed neutropenia, 94% recovered neutrophil counts after stopping antibiotic treatment.…”

“…Importantly, hematologic abnormalities due to antibiotics are not limited to a single class of antibiotics. 30,[32][33][34][35][36][37][38][39][40] Indeed, neutropenia was one of the most common adverse drug-related effects of outpatient parenteral antimicrobial therapy (OPAT) in pediatric patients regardless of the antibiotic agent used. [41][42][43][44] Confirming this finding, Fernandes et al 45 found that leukopenia developed in 6% of pediatric patients on OPAT for a median of 30 days.…”

Clozapine and hematologic adverse reactions: Impact of the Risk Evaluation and Mitigation Strategy program

“…The historical and pre-REMS reporting rates from our study were similar to others in the literature. A population-based case control study 22 conducted in Hong Kong reported a crude odds ratio of 36.0 (95% CI 4.6-284.2) for agranulocytosis with clozapine from January 2004 through December 2013. Another case control study, 23 conducted in Berlin from 2000 through 2010, reported an odds ratio of 49.7 (95% CI 6.0-999.0) for agranulocytosis with clozapine after adjusting for age and sex.…”