ORIGINAL RESEARCH ARTICLE
Investigation into the Impact of Aging on Serious Adverse Events
Associated with Antirheumatic Agents Using the Japanese
Adverse Drug Event Report Database
Published online: 2 June 2018
Ó Springer International Publishing AG, part of Springer Nature 2018
Background With the aging of the population, it is
expected that the number of elderly people with inﬂam-
matory rheumatic diseases will continue to increase.
Objective The purpose of this study was to provide useful
information for risk minimization of antirheumatic agents
using the Japanese Adverse Drug Event Report database
through investigation of the inﬂuence of aging on adverse
events (AEs) in patients treated with tumor necrosis factor-
a inhibitors (TNF-Is) or methotrexate (MTX).
Methods Infections and malignant tumors were selected as
typical serious AEs for antirheumatic agents, which are
indicated in the treatment guidelines for rheumatoid
arthritis. The relationship between age and AEs in patients
treated with TNF-Is or MTX was evaluated by using an
adjusted reporting odds ratio, using the 50–59 years age
group as the reference group.
Results The relative reporting ratio of infections associated
with patients treated with TNF-Is was higher in the group
of patients [ 70 years of age, and lower in the group of
patients \ 50 years of age, compared with the reference
group. The relative reporting ratio of malignant lymphoma
associated with patients treated with MTX was higher in
the group of patients 70–79 years of age compared with the
Conclusion For infections associated with patients treated
with TNF-Is, physicians should take a patient’s age into
consideration when making their observations, with more
careful observation in elderly patients.
The incidence of infections increased with age in
patients treated with antirheumatic agents.
The Japanese Adverse Drug Event Report (JADER)
database is considered to reﬂect actual clinical
practice in the postmarketing stage.
The information from JADER is expected to
contribute to the risk minimization of drugs, and to
be useful for physicians when prescribing a drug
Rheumatoid arthritis (RA) is a chronic inﬂammatory dis-
ease of the joints that causes joint destruction and dis-
ability. In recent years, the treatment of RA has shifted to a
proactive approach using a combination of a biological
product, such as tumor necrosis factor-a inhibitors (TNF-
Is), and conventional synthetic disease-modifying anti-
rheumatic drugs, and it is now possible to control disease
activity and improve function.
As of October 2016, the total population of Japan was
126.7 million, including 34.5 million people over the age
of 65 years. In the total population, the proportion of
elderly was 27.3%, which has been increasing every year
& Yomei Matsuoka
Department of Clinical Medicine (Pharmaceutical Medicine),
Graduate School of Pharmaceutical Sciences, Kitasato
University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641,
Pharm Med (2018) 32:209–217