Management of Inflammatory Rheumatic Conditions in the Elderly

Clément Lahaye; Zuzana Tatar; Jean-Jacques Dubost; Anne Tournadre; Martin Soubrier

Disclosures

Rheumatology. 2019;58(5):748-764. 

In This Article

Ways to Improve Care of the Elderly

Limit Inappropriate Prescribing

The lack of specific studies triggers fears of side effects or insufficient disease control by both the patient and prescriber, leading to innovative therapeutic strategies being least used in the elderly.[75] This results in an underuse of DMARDs, especially the biologics, at the cost of an excessive use of old treatments with uncertain risk/benefit balance (NSAIDs, GCs).[11,13,59,124,125] Though effective and inexpensive, GCs are potentially responsible for hypertension, insulin resistance, weight gain, osteoporosis, fractures, infections, gastric ulcers, adrenal suppression and mortality,[88] and NSAIDs can promote drug interactions, renal failure, cardiovascular events and gastrointestinal bleeding.[126] However, specific data in the elderly population are rare, and ongoing studies such as GLORIA (risk benefit of low dose steroids in elderly RA patients,[127]) will be needed to clarify the place of these molecules in elderly management.

Even though the prescription of boDMARDs has progressed in RA over the last decade, the use of these drugs remains less common in elderly patients,[13,59,124,125,128–132] despite comparable or even higher disease severity and activity.[24] Other common characteristics found in the elderly are associated with a lower likelihood of boDMARD initiation, including less education,[133] low income and living alone.[134] Elderly psoriasis patients tend to be treated with biologics less frequently than younger patients.[103,109,115] Even with an equivalent or higher severity of PsA, the elderly tend to be treated less with TNFi than young patients.[96]

As in other chronic diseases, polypharmacy is particularly frequent in IRD and can promote drug–drug interactions, ADRs and non-adherence.[135] Moreover, in the elderly, polypharmacy is also associated with cognitive impairment, falls and malnutrition.[136] Various strategies have been developed to minimize inappropriate prescribing in multimorbid older people, such as prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool for older people's prescriptions/screening tool to alert to right treatment) criteria, electronic prescribing and close liaison between clinical pharmacists and physicians.[137]

Look for Comorbidities to Refine the Prognosis

The elderly population is characterized by great heterogeneity. Thus, comorbidities and functional limitations are not only determinants of poor HR-QoL, dependency and excess mortality in the elderly,[138–140] but are relevant prognostic factors in the treatment response. Yun et al. reported that use of antidepressants, narcotics or GCs at a dose >7.5 mg at baseline in Medicare RA patients was associated with lower biologic effectiveness (TNFi and abatacept).[141] The biologic effectiveness was greater among non-disabled persons compared with disabled patients (RR = 18; 95% CI: 1.08, 1.28). These results are consistent with data from other studies showing that disability, low functional status and concomitant GC use are inversely associated with the clinical response to treatment with TNFi.[25,28] Other studies have revealed an inverse relationship between the number of comorbid conditions and the probability of attaining remission.[124,129]

In addition to lower efficacy, comorbidities and functional impairment are associated with more side effects. Renal insufficiency has been known for a long time to be a major determinant of MTX toxicity[18] due to impaired MTX elimination.[142] In a registry of 309 MTX-treated patients (first DMARD), the HAQ score (odds ratio = 1.84; 95% CI: 1.12, 3.01) was significantly associated with AEs at 1 year.[143] In retrospective cohorts of boDMARD-treated patients, the presence of comorbidities such as chronic pulmonary disease,[48,51] renal diseases[144] or diabetes mellitus[145] was associated with certain AEs, particularly infectious disease, whereas low functional status and concomitant GC use (>5 mg prednisolone per day) were associated with a higher incidence of AEs.[144,145] In the German biologics registry RABBIT, comorbidities and persistent, highly active disease (mean DAS 28 score >5.1) were significantly associated with increased mortality, even in patients >65 years of age.[146]

A Comprehensive Assessment Serving a Global Strategy

A comprehensive geriatric assessment is a systematic, multidimensional and multidisciplinary approach designed to collect data regarding the medical, nutritional, thymic, social and functional status of elderly patients. This assessment has proven very useful for building an integrated and personalized therapeutic project including pharmacological and non-pharmacological interventions, while preserving HR-QoL and autonomy and limiting mortality.[147] In particular, screening and preventing depression, denutrition and mobility limitations are efficacious ways of improving the HR-QoL and survival of the elderly.

A meta-analysis of 72 studies including 13 189 RA patients revealed that depression is highly prevalent (between 15 and 35% according to the type of criteria used), even if older patients seem to be at lower risk than younger subjects.[148] In a German longitudinal database, depression was present in 22% of the 1072 elderly RA patients (mean age 72 years), and dementia, cancer, osteoporosis, hypertension and diabetes were associated with a higher risk of developing depression.[149] Moreover, depression is associated with increased global mortality in RA,[150] suicide death in RA and PsA,[151] and reduced likelihood of joint remission in RA and PsA.[152,153] However, anti-depressants are frequently associated with side effects and have inconstant benefits in pain management or functional status.[154] More specific studies would be needed to evaluate the interest of pharmacological and non-pharmacological treatment for depressed elderly.[155]

Rheumatoid cachexia is characterized by an involuntary reduction in lean body mass (LBM) associated with normal or even increased fat mass,[156] and is observed in 26–71% of RA patients.[157] Low muscle function is often related to this low LBM, defining sarcopenia.[158] As bone and muscle are critically linked, low LBM and higher fat mass are associated with osteopenia, even after adjusting for age, race, gender and height.[159,160] Major fractures and sarcopenia are essential prognostic issues in the elderly for both HR-QoL and mortality.[161–163] In RA, the negative effect of low lean mass on walking speed is potentialized by ageing, depression, pain, cumulative GC exposure and non-treatment with DMARDs.[164] Adequate control of disease activity in combination with appropriate physical exercise and increased calcium/vitamin D and protein intake are efficient strategies for controlling rheumatoid cachexia, cardiovascular risk and risk of fracture, and preserving autonomy.[156,165,166] Thus, all types of physical activities, including walking or aerobic and strengthening exercises, have exhibited modest benefit in cardiovascular risk, disease-related outcomes, inflammation and HR-QoL in IRD, but without significant side effects.[167,168]

Concerning nutritional intervention, the effects of antioxidant-rich and omega-3 fatty acid-rich diets (e.g. Mediterranean diets) are inconsistent.[169] A high dose omega-3 regimen (3–5 g/day) has been shown to improve disease-related activity markers in RA.[170] Restrictive diets and fasting, although potentially effective on disease activity in healthy middle-aged patients, could be particularly deleterious in the aged subject and must be avoided. Thus, no study has been conducted specifically with elderly subjects.

Towards new Study Designs to Support Specific Recommendations

Although current studies are more interested in the elderly population, they continue to evaluate the benefits of interventions using tools best adapted to younger patients. Regarding the elderly, the actual value given to clinical/biological/radiological criteria for activity seems rather disproportionate. The clinical relevance of therapeutic strategies should be assessed by their impact on HR-QoL, autonomy and mortality related to cardiovascular diseases or cancers. This will require broader criteria and longer-term assessments. These new evaluation criteria should then be considered in management strategies, which currently almost exclusively consider the IRD activity criteria.[16]

Recent therapeutic developments have occurred rapidly, particularly when considering non-TNFi biologics. Their precise place among the therapeutic strategies needs to be re-evaluated: as second-line after relapse or as first-line in patients at risk of complications with conventional treatments. This issue appears to be particularly relevant for frail comorbid subjects. Therefore, further studies will be required to validate the most effective therapeutic strategies to best adapt the existing recommendations and guidelines.

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