SAN DIEGO—Older adults with rheumatoid arthritis (RA) comprise two groups: those who have lived with diagnosed RA since an early age (young-onset RA) and those who have new-onset RA diagnosed at an older age (≥65 years), known as late-onset RA or, formerly, as elderly onset RA.1 Individuals with late-onset RA have more acute and systemic presentation of symptoms than individuals with young-onset RA.1 The more striking and concerning difference, from a treatment perspective, is that individuals with late-onset RA are less likely than individuals with young-onset RA to be treated with disease-modifying anti-rheumatic drugs (DMARDs), which are the standard of care for RA.
RA treatment guidelines recommend a treat-to-target approach, with early, aggressive use of DMARDs to prevent chronic deformity and disability.2 Although we lack age-specific guidelines, studies have shown that treat to target is effective and achievable in late-onset RA, with an acceptable safety profile.
Evidence suggests, however, that we are far from achieving this goal in usual care for older adults. Lee and colleagues [Editor’s note: research by one of the authors] found that less than 30% of older Medicare beneficiaries with a new diagnosis of late-onset RA are started on some form of DMARD within a year of diagnosis.3 This is in contrast to 70–80% of younger adults with RA receiving DMARDs. Other studies have also reported that older adults receive less aggressive RA care.4
Why is DMARD utilization in late-onset RA low? Are we mistreating older adults, or do barriers exist in the real world that prevent DMARD utilization in older adults? Several real-world challenges were reviewed in the session titled Are You Ready for the Silver Tsunami? at ACR Convergence 2023, which we summarize here.
DMARDs in the Real World
Physiologic challenges
Aging is a physiologic process associated with changes in dynamic biological, environmental, psychological, behavioral and social processes that lead to irreversible functional decline across all biologic systems.5 The multisystem decline in function affects drug pharmacokinetics and pharmacodynamics. For example, renal blood flow and glomerular filtration rates are reduced with aging, even in the absence of any underlying pathology.6 Thus, serum creatinine as a sole measure of renal function can be inadequate and misleading in older adults. It is best to calculate the creatinine clearance to inform medication dosing in older adults, especially those medications that are excreted renally. Methotrexate, the first-line DMARD for moderate to severe RA, almost exclusively has renal excretion. It is no surprise that studies of methotrexate use in older adults report use of lower doses (~10 mg/weekly).7
Similar physiologic declines occur in other systems in older adults, namely changes in the gastrointestinal tract, leading to altered absorption; changes in the hepatic system, leading to altered metabolism; and altered body composition, affecting drug distribution.
The 5 Ms
The need for aging-sensitive care led our colleagues in geriatrics to develop essential guiding principles to systematically identify and address the complexity of the rapidly growing older adult population: the 5 Ms—mind, mobility, multimorbidity, medications (i.e., polypharmacy) and what matters most (i.e., patient preference).8 The guiding principles of the 5 Ms can inform how we optimize DMARD use in older adults with RA and manage the greater burden of geriatric conditions that can impact outcomes.
Conditions of the mind (e.g., cognitive impairment and dementia) present unique challenges in DMARD utilization in older adults. Those with mild cognitive impairment living in the community may have difficulty managing their medications, coming in for follow-up visits and getting timely blood work to monitor for toxicity associated with DMARD use in RA.
Those with moderate to severe dementia pose practical and ethical dilemmas: Can we accurately assess disease activity when patients cannot communicate their symptoms? Can we really push for treat to target in RA patients with moderate to severe dementia?
Similarly, late-onset RA patients in the community with preexisting mild to moderate mobility limitations face challenges in managing DMARD therapy. Such patients need resources for medication management and transportation for follow-up visits. In addition to functional limitations, frailty, propagated by age and inflammation, can have an impact on mobility and health outcomes in older adults with late-onset RA, creating another dilemma for initiating aggressive DMARD therapy: multimorbidity and polypharmacy (medications), common in older adults and a natural consequence of aging, complicate the choice of DMARD due to increased risks of drug-drug and drug-disease interaction.
The final M, matters most, refers to patient preference. Often, patient preference is clouded by ageist biases toward themselves. An older adult may decline DMARD initiation stating, “I’m too old for aggressive treatment.” A patient’s family members and caregivers may share a similar philosophy and prefer a treatment that relieves pain rather than one that treats the underlying disease.
Physicians may also harbor ageist biases, mostly stemming from fear of causing harm. Some evidence suggests that DMARDs may be associated with increased toxicity in older adults, especially biologic DMARDs, fueling caution to avoid harming these patients.9 Of concern, despite growing evidence of the risks of glucocorticoid use, older adults with late-onset RA are commonly prescribed long-term glucocorticoids—with or without DMARDs.
In Sum
Many real-world challenges interfere with efforts to optimize the utilization of DMARD therapy for patients with late-onset RA. A need exists for increased clinical and research experience in older adults to provide data-driven practice for patients with late-onset RA. Dedicated geriatric rheumatology clinics with elements of the 5Ms incorporated within the practice will provide clinical experience. Dedicated trials and longitudinal observational studies will provide much-needed, nuanced evidence for best practice to improve the care of older adults with late-onset RA.
Devyani Misra, MD, MS, is board certified in rheumatology and geriatrics. She is affiliated with Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
Jiha Lee, MD, MHS, is a rheumatologist at the University of Michigan, Ann Arbor.
References
- van Schaardenburg D, Breedveld FC. Elderly onset rheumatoid arthritis. Semin Arthritis Rheum.1994 Jun; 23(6):367–378.
- Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2021 Jul;73(7):1108–1123.
- Lee J, Martindale J, Makris UE, et al. Initiation of disease-modifying antirheumatic drugs in older medicare beneficiaries with new diagnosis of late-onset rheumatoid arthritis. ACR Open Rheumatol. 2023 Dec;5(12):694–700.
- Schmajuk G, Schneeweiss S, Katz JN, et al. Treatment of older adult patients diagnosed with rheumatoid arthritis: Improved but not optimal. Arthritis Rheum. 2007;57(6):928–934.
- Guo J, Huang X, Dou L, et al. Aging and aging-related diseases: From molecular mechanisms to interventions and treatments. Signal Transduct Target Ther. 2022 Dec;7(1):391.
- Aymanns C, Keller F, Maus S, et al. Review on pharmacokinetics and pharmacodynamics and the aging kidney. Clin J Am Soc Nephrol. 2010 Feb;5(2): 314–327.
- Tutuncu Z, Reed G, Kremer J, Kavanaugh A. Do patients with older-onset rheumatoid arthritis receive less aggressive treatment? Ann Rheum Dis. 2006; 65(9):1226–1229.
- Molnar F, Frank CC. Optimizing geriatric care with the geriatric 5 Ms. Can Fam Physician. 2019 Jan;65(1):39.
- Dalal DS, Duran J, Brar T, et al. Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to young: A systematic review and meta-analysis. Semin Arthritis Rheum. 2019 Apr;48(5):799–807.
