Targeting Low Disease Activity in Elderly-Onset Rheumatoid Arthritis: Current and Future Roles of Biological Disease-Modifying Antirheumatic Drugs

Drugs & Aging, Jan 2016

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 acute-phase 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 non-TNF 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 pre-frail 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.

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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)


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Takahiko Sugihara, Masayoshi Harigai. Targeting Low Disease Activity in Elderly-Onset Rheumatoid Arthritis: Current and Future Roles of Biological Disease-Modifying Antirheumatic Drugs, Drugs & Aging, 2016, pp. 97-107, Volume 33, Issue 2, DOI: 10.1007/s40266-015-0341-2