1. Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources.
- Author
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Curtis JR, Perez-Gutthann S, Suissa S, Napalkov P, Singh N, Thompson L, and Porter-Brown B
- Subjects
- Aged, Arthritis, Rheumatoid mortality, Cardiovascular Diseases chemically induced, Cardiovascular Diseases epidemiology, Chemical and Drug Induced Liver Injury epidemiology, Europe, Female, Gastrointestinal Diseases chemically induced, Gastrointestinal Diseases epidemiology, Humans, Incidence, Japan, Male, Middle Aged, Survival Rate, United States, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Arthritis, Rheumatoid drug therapy, Clinical Trials as Topic statistics & numerical data, Product Surveillance, Postmarketing statistics & numerical data
- Abstract
Objectives: To evaluate the magnitude of serious adverse events (SAEs) observed in postmarketing reports of tocilizumab (TCZ) for rheumatoid arthritis (RA) in relation to SAEs observed in TCZ clinical trials and external epidemiology data., Methods: A total of 64,000 patient-years (PY) of TCZ exposure was needed to determine, with 90% power, whether rates of SAEs of interest (eg, death, hepatic, gastrointestinal, and cardiovascular) were ≥50% higher (agreed with the Food and Drug Administration) than expected. Reporting rates were calculated for spontaneously reported SAEs, open-label or unblinded postmarketing clinical trials (phase 3b/4), and a Japanese postmarketing surveillance program in the global postmarketing safety database. Event rates were calculated for the registrational placebo-controlled trials and long-term extension data. External comparators for anti-tumor necrosis factor (aTNF)-treated RA patients were derived from a US-based health care insurance claims database or published literature., Results: The global postmarketing safety database provided 65,099 PY of TCZ exposure; the aTNF external comparator population provided 53,360 PY. Spontaneous reporting rates per 100 PY (95% confidence interval) were 8.3 (8.1, 8.5) SAEs, 0.39 (0.34, 0.44) deaths, 0.06 (0.04, 0.08) serious hepatic events, 0.15 (0.12, 0.18) serious gastrointestinal events, 0.09 (0.07, 0.12) serious myocardial infarctions, 0.15 (0.12, 0.18) serious strokes, and 0.07 (0.05, 0.09) cardiac deaths in the global postmarketing safety database. These were of similar magnitude to corresponding rates from registrational clinical trials, the aTNF external comparator population, and published literature., Conclusions: SAE rates observed among postmarketing TCZ users were similar to those of various comparison populations. Predetermined design of studies to compare postmarketing AEs using multiple data sources is a useful strategy that can be applied to other medications., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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