The concept of rheumatoid arthritis (RA), a chronic progressive inflammatory disease of the synovial joints, as a disorder of middle age is changing to include patients outside the range of 40 to 60 years. In particular, the prevalence of RA is reported as 2% of the population older than 60 years and may actually be much higher.1
The increase in RA among the elderly can be attributed to two main factors: 1) patients diagnosed with young-onset RA (YORA) are living longer due to better management; and 2) increasing numbers of patients are being diagnosed with elderly-onset RA (EORA). In a 2017 retrospective study from Japan,2 investigators reported that the mean age of onset had rapidly increased over the previous decade from 55.8 years in 2002-2003 to 59.9 years in 2012-2013, with a corresponding shift in peak age from 50-59 to 60-69 years during that same period of time.
Causes Leading to Increasing Prevalence
One question clinicians and researchers alike have been asking is: “Does this represent different forms of the disease or a continuum of RA diagnosed at different stages?” In a 2007 review, authors Tutuncu and Kavanaugh1 suggested that “diagnostic imprecision” may be a factor in prevalence rates, as clinicians may have difficulty differentiating RA in the elderly from other common rheumatic diseases such as polymyalgia rheumatica, calcium pyrophosphate deposition disease, gout, and osteoarthritis.
In contrast, a 2017 review by Kobac and Bes3 found that the patient profile of EORA differed in important ways from YORA in the elderly. Later diagnosis (EORA) was associated with a more heterogeneous distribution according to sex, frequency of disease flares, and more frequent involvement of large joints, along with less consistency of rheumatoid factor (RF) positivity. At the same time, patients with EORA were likely to be diagnosed earlier in the disease course, leading to less erosive damage and little or no history of disease-modifying antirheumatic drug (DMARD) use at the same age as older patients with YORA.
Likewise, a 2016 cross-sectional study of 971 patients in the Ontario Best Practices Research Initiative by Ruban et al4 found basic differences in disease presentation, including higher swollen joint counts, increased C-reactive protein levels, and greater comorbidity burden in patients with EORA compared with those with YORA.
Are the Prognoses Different?
Prognostically, it is still not clear which group fares better.3 Studies using RF and anti-cyclic citrullinated peptide (anti-CCP) antibodies — standard prognostic markers for YORA — are not reliable for predicting outcomes in EORA. “The etiology of older-onset RA is likely very similar, but these patients have less likelihood of positive RF and anti-CCP,” explained Janet Pope, MD, MPH, FRCPC, division head in rheumatology at St. Joseph’s Health Centre, London, Ontario, Canada. “They also start more acutely (have shorter disease duration) and have higher inflammation on average at baseline.” She observed that the distinct pattern of EORA suggests that age does modify (on average) the presentation of the patient with new RA. Dr Pope cautions that it is still unknown, however, to what degree elderly patients with smoldering YORA are simply not being diagnosed or appropriately referred.
When considering differences in therapeutic responses, Dr Pope told Rheumatology Advisor: “The outcomes of response to therapy in early RA are similar in the oldest quartile of patients compared to the rest, if you adjust for baseline differences. Elderly patients present with more elevated inflammatory markers, are on more prednisone at baseline visits, and show slightly higher baseline disease activity, but their change in disease status is the same as younger patients. So if you start off a bit worse, you end up a bit worse.”
Targeting Therapy for the Elderly Patient With RA
Studies have suggested that patients with EORA may be less aggressively treated than they should be.1,4 The Ruban study reported that despite higher disease activity at diagnosis, patients with EORA were less likely to receive combination DMARD therapies or biologic agents compared with patients with YORA.4 Dr Pope, a coauthor of this study, explained that this may in part be due to access, as public payers take longer than private payers to recognize criteria for use and issue approval of advanced therapeutic agents.
“The purpose of treatment (target) may be different in a very old patient,” Dr Pope said. “For instance, an 80-year-old doesn’t have likely 20 years of future RA damage, whereas a 50-year-old does.” She reported that the goal for a very elderly person with RA may be to maintain function and independence now and in the short term, while for a young person with RA it is to help now and in the near future and long term (to prevent damage).
“There are not really any major studies that suggest age dramatically affects response to treatment in RA,” Dr Pope said. Elderly patients without comorbidities that would preclude specific treatment can be offered similar treatment as younger patients, and she noted that methotrexate is used in both younger and older patients with RA.
Which Agents Are Best?
“Everyone with active RA should be offered traditional DMARDs as soon as possible, unless there is a contraindication,” Dr Pope stated. “At any age, if these drugs do not work for a patient to meet the target (remission, low disease activity) or are not tolerated and the disease is still active, then other drugs should be offered if not contraindicated, such as advanced therapeutics (biologics, Janus kinase inhibitors).”
“After all the above are considered, then you may consider what is the most efficient and cost-effective approach to treating an individual patient,” Dr Pope suggested. “I have patients who are in their late 80s and older where, if they are well controlled, I only lower their DMARD treatment for safety reasons (such as lowering methotrexate dose, as kidney function declines with age).”
- Tutuncu Z, Kavanaugh A. Rheumatic disease in the elderly: rheumatoid arthritis. Rheum Dis Clin North Am. 2007;33(1):57-70.
- Kato E, Sawada T, Tahara K, et al. The age at onset of rheumatoid arthritis is increasing in Japan: a nationwide database study. Int J Rheum Dis. 2017;20(7):839-845.
- Kobak S, Bes C. An autumn tale: geriatric rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018;10(1):3-11.
- Ruban TN, Jacob B, Pope JE, Keystone EC, Bombardier C, Kuriya B. The influence of age at disease onset on disease activity and disability: results from the Ontario Best Practices Research Initiative. Clin Rheumatol. 2016;35(3):759-763.