Targeting Low Disease Activity in Elderly-Onset Rheumatoid Arthritis: Current and Future Roles of Biological Disease-Modifying Antirheumatic Drugs
Drugs Aging
Targeting Low Disease Activity in Elderly-Onset Rheumatoid Arthritis: Current and Future Roles of Biological Disease-Modifying Antirheumatic Drugs
Takahiko Sugihara 0 1 2
Masayoshi Harigai 0 1 2
Key Points 0 1 2
0 Department of Epidemiology and Pharmacoepidemiology, Institute of Rheumatology, Tokyo Women's Medical University , 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054 , Japan
1 Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital , 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015 , Japan
2 Masayoshi Harigai
Elderly rheumatoid arthritis (RA) is classified into two clinical subsets, elderly-onset RA (EORA) and younger-onset elderly RA. With the improvement of life expectancy in the general population and advent of the super-aging society, the number of patients with EORA is anticipated to increase. Both large and small joints are affected initially at onset, and individuals with early EORA have higher scores of disease activity and levels of acutephase reactants than those with early younger-onset RA. EORA is a progressive disease similar to younger-onset RA. Tumor necrosis factor (TNF) inhibitors are equally or slightly less effective in elderly patients than in younger patients with RA, and disease duration may have a greater impact on disease outcomes than age. Evidence of nonTNF biological disease-modifying antirheumatic drug use in EORA is limited. TNF inhibitors may not increase the risk for infection in elderly patients any more than methotrexate; however, increasing age is an independent and strong risk factor for serious infections in patients with RA. Treatment choice in patients with EORA is strongly influenced by comorbidities, especially cardiovascular disease, chronic lung disease, and frailty. To prevent progression to irreversible geriatric syndromes, non-frail patients with EORA, who are aging successfully should undergo intensive treatment using the treat-to-target strategy, and pre-frail and frail patients with EORA should be treated with the aim of returning to a non-frail or prefrail stage, respectively. An appropriate treatment strategy for EORA and younger-onset elderly RA should be developed in the next decade using a multi-disciplinary approach.
1 Introduction
Over the past decade, the clinical development and
approval of various types of biological disease-modifying
antirheumatic drugs (bDMARDs) along with new
classification criteria [
1
] and a novel treatment strategy has
brought about tremendous changes in the outcomes of
treatment for rheumatoid arthritis (RA). Early diagnosis
and immediate initiation of treatment with conventional
synthetic DMARDs (csDMARDs), primarily methotrexate
(MTX), constitute the mainstream treatment for
middleaged patients with RA. Treating RA to target is a consensus
strategy in this population [
2, 3
]; prospective cohort studies
and randomized controlled trials (RCTs) showed that
aiming at remission or low disease activity (LDA) by
strategic switching of DMARDs is a realistic and
practicable approach in patients with RA [
4–7
] and conveys
better outcomes than routine care [
8
].
In the treatment of RA with treat-to-target strategy,
bDMARDs are indispensable. The European League
against Rheumatism (EULAR) Task Force recommended
that in patients responding insufficiently to MTX and/or
other csDMARDs, with or without glucocorticoids, a
bDMARD [tumor necrosis factor (TNF) inhibitor, T-cell
costimulation inhibitor or interleukin-6 receptor-blocking
monoclonal antibody, and under certain circumstances,
anti-B-cell agent] should be commenced [
9
]. A 2014
update of recommendations on treating RA to target
emphasized that the choice of the composite measure of
disease activity and the target value is influenced by
comorbidities, patient factors, and drug-related risks [
3
].
Such influencing factors are frequently observed in patients
with elderly RA, which makes treatment of this patient
population very challenging. In this article, we review the
clinical features of elderly-onset RA (EORA),
effectiveness and safety of bDMARDs in elderly RA, and obstacles
that prevent rheumatologists from providing standard
treatment to EORA patients as well as the
countermeasures, and discuss priorities for future research in this
growing field of rheumatology.
2 EORA
2.1 Definition
Elderly RA is categorized into two clinical subsets; EORA
and younger-onset elderly RA [
10
]. Onset after 60 years of
age is mainly adopted as the classical definition of EORA
in the literature. This definition of EORA has been used
throughout this review unless otherwise specified, although
we recognize that elderly individuals are generally
healthier in the current aging society than ever and the
definition of elderly-onset should be validated or modified
in future.
2.2 Epidemiology
Previous epidemiological studies showed a declining trend
in the incidence rates of RA in the period 1955–1994 [
11
].
However, the incidence rate o (...truncated)