Age is an inherent dimension of inflammatory rheumatic disease (IRD), with the incidence of rheumatoid arthritis (RA) shown to increase with age.1 In addition, patients with RA have a higher risk of developing other comorbidities than those without RA,2 leading to higher morbidity with advancing age. The dual effects of age and IRD can create overlapping disease manifestations that amplify and complicate each other, and pose unusual challenges for both diagnosis and treatment in an older population. As the global population ages, understanding and meeting the challenges in this patient group is becoming more important.

Challenges of Aging With IRD

Individuals in the general population aged 65 years and older are at an increased risk of developing multifactorial conditions, often referred to as geriatric syndromes,3 which do not correspond to distinct disease entities.

One example is frailty, which incorporates factors that overlap with other geriatric syndromes, such as sarcopenia, exhaustion, and low physical activity. Other important geriatric syndromes include malnutrition, susceptibility to falls, cognitive impairment, and incontinence. Multimorbidity occurs as patients accrue these syndromes and later-life disorders, such as cardiovascular conditions. Managing these mutually reinforcing problems can lead to polypharmacy.1,3


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In a similar manner, the phenotype of IRD can include exhaustion and low activity. Multimorbidity and polypharmacy are hallmarks of IRD regardless of patient age. However, IRD can broadly affect the aging process. Frailty is more common in older adults with IRD than without IRD.1 Polypharmacy in older adults with RA carries higher than usual risk of aggravating organ stress, falling risk, and possibly infection.4 Often cardiovascular disease (CVD) risk is higher,5 with elevated risk for myocardial infarction and mortality. Risk prediction models for CVD in the general population inaccurately predict adverse events in patients with IRD.5 In addition, cognitive impairment risk is elevated in patients with systemic lupus erythematosus (SLE), and may also be higher in patients with RA.6 Increasing age may amplify the effect of IRD, leading to more profound cognitive functional deficits.

Aging itself also affects IRD, with the disease phenotype in older adults with IRD being different from that in younger patients. For example, falls appear to be relatively common in RA, but especially among older adults. Joint involvement is more severe in late- than in early-onset psoriatic arthritis (PsA). Nonspecific inflammatory markers, such as interleukin (IL)-6, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), are often higher in patients with late-onset RA and PsA compared with patients with early-onset RA and PsA. More specific markers such as tumor necrosis factor (TNF) α, rheumatoid factor, and anticitrullinated protein antibody (ACPA) are lower in patients with late-onset RA and PsA compared with patients with early-onset RA.3

Despite such distinctions, diagnosis can be challenging in older adults with IRD. For example, clinical characteristics of seronegative late-onset RA tend to overlap with polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema.7 With advancing age, severe digital osteoarthritis also becomes more difficult to distinguish from RA.

Measuring Deficits and Risk

A variety of specialized assessment tools exist to identify and measure frailty in older adults; some of these may apply to those also with IRD. They fall into categories informed by either a “phenotype perspective”8 or a “cumulative-deficit perspective.”9 The “Fried phenotype” frailty screening method, for example, incorporates primarily physical variables, such as grip strength, low activity, and exhaustion. Screenings of this type, primarily suited to identify risk for adverse events,1 are relatively easy to administer. These tools typically do not incorporate data in the cognitive, psychologic, social functioning, or nutritional domains, and do not suggest treatment options. In contrast, more complex processes, such as comprehensive geriatric assessment (CGA), in addition to medical history and physical status, incorporate a broader range of psychosocial and functional data. As in the case of CGA, they may extend beyond a purely diagnostic process to inform treatment decisions.10

Treatment Considerations

Patients, their caregivers, and treating rheumatologists must discuss and harmonize priorities for interventions, with a focus on alleviation of symptoms and independent functioning. Treatment goals between patient and provider may not completely overlap, suggesting protocols for tight disease control. However, early qualitative survey research suggests that some rheumatologists actively incorporate patient perspectives, by giving a higher priority, when appropriate, to preserving function at a patient-selected level rather than a treat-to-target approach.11

Given the challenges posed by multimorbidity and polypharmacy, rheumatologists may also consider co-management with a geriatrician. Leveraging the expertise of a geriatrician can facilitate treatment aligned with the “geriatric 5M” dimensions: mind, mobility, medications, multicomplexity, and “matters most” (ie, identifying priorities and preferences of patients and caregivers). Including the perspective of a geriatrician can also facilitate completion of a CGA.10

Barriers and Gaps in Knowledge

There is a lack of literature on the CGA process outcomes and collaborative care models, specifically for older adults with IRD. Further research is needed to identify the conditions under which co-management would most benefit patient outcomes. Meanwhile, barriers to implementing a formal collaborative model may include limited specialist availability and lack of reimbursement, such as for outpatient social work, pharmacy, and nutrition services. It is known that CGA requires only a small amount of time and availability of professionals to administer and coordinate testing.10

Treatment guidance is still evolving regarding risk for CVD in older adults with IRD. For example, the European Alliance of Associations for Rheumatology (EULAR) task force5 guidelines have suggested that CVD risk estimates should be modified for patients with IRD, such as by applying a multiplier of 1.5. However, these recommendations have not been stratified by age. It also remains unclear whether target values for blood lipids or blood pressure should differ across disease phenotypes regarding age, such as for patients with late-onset disease or in older adults with early-onset disease. Similarly, current consensus documents for physical activity and other lifestyle factors in IRD do not have many recommendations specifically for older adults.5

Gaps also remain in knowledge of the burden of cognitive impairment in later-life rheumatic diseases. For example, it is uncertain whether risk for cognitive decline is elevated in PsA or ankylosing spondylitis, as it appears to be in RA and SLE. In part, this reflects the additional limitation that much of the scientific literature on the impact of aging on IRD is specific to RA. As with the broader aging population, there is also little consensus regarding how to mitigate additional cognitive impairment secondary to rheumatic disease.6 However, amid these uncertainties, as the effects of diverse rheumatic diseases are recognized, the challenges of preserving both physical and cognitive function is taking on new urgency in aging societies.

References

  1. Salaffi F, Farah S, Di Carlo M. Frailty syndrome in rheumatoid arthritis and symptomatic osteoarthritis: an emerging concept in rheumatology. Acta Biomedica Atenei Parm. 2020;91(2):274-296. doi:10.23750/abm.v91i2.9094
  2. England BR, Roul P, Yang Y, et al. Burden and trajectory of multimorbidity in rheumatoid arthritis: a matched cohort study from 2006 to 2015. Ann Rheum Dis. 2021;80(3):286-292. doi:10.1136/annrheumdis-2020-218282
  3. van Onna M, Boonen A. Challenges in the management of older patients with inflammatory rheumatic diseases. Nat Rev Rheumatol. Published online 2022:1-9. doi:10.1038/s41584-022-00768-6
  4. Widdifield J, Bernatsky S, Paterson JM, et al. Serious infections in a population‐based cohort of 86,039 seniors with rheumatoid arthritis. Arthritis Care Res. 2013;65(3):353-361. doi:10.1002/acr.21812
  5. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28. doi:10.1136/annrheumdis-2016-209775
  6. Meade T, Manolios N, Cumming SR, Conaghan PG, Katz P. Cognitive impairment in rheumatoid arthritis: a systematic review. Arthritis Care Res. 2018;70(1):39-52. doi:10.1002/acr.23243
  7. Bajocchi G, La Corte R, Locaputo A, Govoni M, Trotta F. Elderly onset rheumatoid arthritis: clinical aspects. Clin Exp Rheumatol. 2000;18(4; SUPP/20):S-49.
  8. Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M157. doi:10.1093/gerona/56.3.M146
  9. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal. 2001;1:323-336. doi:10.1100/tsw.2001.58
  10. Ward KT, Reuben DB. Comprehensive geriatric assessment. In: UpToDate, Waltham, MA. Vol 4. Accessed April 29, 2022:09-21.
  11. Nawrot J, Boonen A, Peeters R, Starmans M, van Onna M. Rheumatologists’ views and experiences in managing rheumatoid arthritis in elderly patients: a qualitative study. J Rheumatol. 2018;45(5):590-594. doi:10.3899/jrheum.170773