The influence of ageing on the development and management of rheumatoid arthritis

Abstract

The population of elderly individuals with rheumatoid arthritis (RA) is expanding, due mainly to increasing life expectancy. A variety of theories have been proposed to explain the ageing process, including accumulation of DNA damage and resultant changes in biological processes. Such changes can influence the development and/or course of disease. Furthermore, alterations in biological function determine the biological age-as opposed to chronological age-of an individual, which strongly influences their ability to cope with disease. Moreover, comorbidities are more frequent in elderly individuals. Together, these factors complicate treatment of disease and necessitate careful patient management. Indeed, although evidence from clinical trials suggests that DMARDs and biologic agents have good efficacy and are well tolerated in elderly patients with RA, such individuals are often undertreated and inadequately managed. Unfortunately, insufficient data are available for the development of evidence-based guidelines for this population, as elderly patients are often excluded from clinical trials owing to age restrictions or comorbidities. Thus, additional clinical studies in elderly patients are warranted, with treatment regimens tailored according to vitality or frailty parameters. This Review focuses on the pathophysiological aspects of ageing and their implications for the management of RA in elderly patients.

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

“…Interestingly, RA is characterized by accelerated signs of immunosenescence, regardless of disease duration or the age of onset [11]. Changes observed in the immune system of RA patients are similar to those in the elderly, leading ultimately to breach of self-tolerance.…”

“…The CD4+CD28-cells may acquire NK-like functionalities [16], produce more proinflammatory cytokines and become resistant to apoptosis [17]. These cells are prone to react with self-antigens and it comes as no surprise that CD4+CD28-populations are increased in several auto-immune diseases, RA in particular [11]. The CD8+CD28-cells become unable to produce cytokines, but acquire the ability to suppress antigen-presenting function of DCs.…”

“…This affects both the innate as well as the adaptive arms of the immune system and results in a decreased capacity to resolve infections, but also in pro-inflammatory changes and breaks in self-tolerance. The aging of the innate immune system leads to the dysregulation of dendritic cells (DCs), neutrophils, Natural Killer (NK) cells and macrophages with increased production of pro-inflammatory cytokines and higher circulating levels of TNF, IL-6, C-reactive protein (CRP) and other pro-inflammatory molecules, creating a pro-inflammatory environment [11,13]; this process is described sometimes as "inflammaging" [14] .…”

“…Elderly patients with RA suffer more from comorbidities such as hypertension, diabetes mellitus, chronic obstructive pulmonary and cardiovascular disease 5 than younger patients [10], often resulting in polypharmacy and an increased risk of drug interactions. Specific geriatric conditions, such as cognitive impairment, depression, malnutrition, sensory limitations, mobility restrictions and incontinence result in decreased functional capacity and reduced ability to withstand or compensate for acute or chronic illness [11]. The concept of frailty is used to define an inevitable multifactorial progression toward functional decline.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Also mainly due to increasing life expectancy, the population of elderly individuals with rheumatoid arthritis (RA) is expanding [20]. This is noteworthy because people with RA die at a younger age than people without the disease, whereas age exerts an exponentially increasing effect on CVD risk in RA patients [21].…”