Rheumatoid arthritis (RA) is a chronic disease of complex pathophysiology occurring in immunogenitically susceptible hosts. Uncertainties about the pathogenesis of RA, the variability of its course and diversity of its prognosis make management difficult. In part two of this two part article, Professor Yasser El Miedany discusses the management of RA in the elderly, and reviews the different treatment options
First published in February 2006, updated May 2021
Rheumatoid Arthritis (RA) is a chronic disease of complex pathophysiology occurring in immunogenitically susceptible hosts. Uncertainties about the pathogenesis of RA, the variability of its course and diversity of its prognosis, as well as the disease’s effect on the patients’ lives make management and therapeutic interventions a relatively difficult matter.
This challenge becomes even more complicated in the older adult who might be suffering from comorbidity masking or mimicking systemic effects of RA. Apart from drawing up a treatment plan, the physician has to consider the implications the disease and its treatment might have on the patient’s independence, their quality of life, their and their family’s social life and last but not least their financial situation. The chronicity of RA often necessitates long-term follow up and sometimes warrants changes to the management plan, which are only feasible if cognitive function is not impaired.
Treatment of RA in the elderly
Treatment of RA is a complex procedure. The chronicity of the disease, its variable expression with remissions and exacerbations and its implications for the patient’s life must be taken into account and the therapeutic decision must be adapted to the individual patient at any particular time. The initial steps in the management of RA are to establish the diagnosis, perform a baseline evaluation and estimate the prognosis. Setting of the goals of therapy must logically precede the development of the individual management strategy. In general the main goals should include:
- Relieve patient’s pain and other articular symptoms
- Improve mobility and function
- Alter the long-term progression of the disease.
However, in some instances, a limited goal such as regaining the ability to walk by hip or knee prosthesis may be more useful for the patient than a modest reduction in the general severity of the disease.
Non-pharmacologic treatment of RA
Optimal management of RA involves more than pharmacologic therapy. Early in the course of the disease, the patient needs to learn to accept that he or she will be living with RA and will need to become involved in the process of making decisions about treatment. If treatment does not fully control the disease, the patient may struggle emotionally as well as physically in adjusting to this chronic disease, its flares and the concomitant loss of function. Geriatricians, rheumatologists, their office staff and their primary care colleagues play important roles in educating the patient and the patients’ family about the disease and providing longitudinal supervising care. Instruction in joint protection, conservation of energy and a home programme of joint range of motion and strengthening exercises are important in achieving the treatment goal of maintaining joint function. Physical and occupational therapy may help the patient who is compromised in activities of daily living. Regular participation in dynamic and even aerobic condition exercise programmes improves joint mobility, muscle strength, aerobic fitness and function as well as psychological well being without increasing fatigue or joint symptoms1–4.
Pharmacologic treatment of RA
Older adults are particularly susceptible to adverse drug reactions. In one study5, three per cent of hospital admissions for older adults resulted from adverse reactions related to anti-inflammatory therapy either as a direct consequence of the medication such as gastrointestinal (GI) bleeding or indirectly by exacerbating an underlying medical condition, such as worsening congestive heart failure or renal insufficiency.
The initial strategy for treating older patients with RA is to palliate the pain caused by the inflammatory synovitis. Although Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are among the first line treatment in younger RA patients, the high daily doses that are required to provide pain relief cause considerable toxicity in older patients including renal insufficiency, hypertension, oedema, exacerbation of congestive heart failure and mental status changes6. One survey showed that older adults taking six different medications were 14 times more likely to have adverse reactions than a younger person taking the same medications7,8. Therefore, it must be clarified to the patient that this is not a long-term therapy but to help to ease the pain as a temporary option until the arthritis gets controlled.
Although the risk of bleeding is markedly reduced with the cyclo-oxygenase-2 (COX-2) inhibitors, all of the above mentioned side effects are still seen with these agents. Furthermore, the recall of rofecoxib (Vioxx) by its manufacturer (Merck) raised the attention to the cardiovascular safety of COX-2 inhibitors. This concern has recently been extended to involve all NSAIDs both traditional and selective, based on the fact that both groups of drugs inhibit COX-2 enzyme. Thus, in providing treatment for this vulnerable group of patients, care should be given to assess the risk and avoid treatment that can cause worse complications than the disease for which they are prescribed. A simple way to assess for the risk related to NSAIDs (including COX-2 inhibitors) is using the non-steroidal anti-inflammatory risk assessment questionnaire that can be completed by the patients or their carers while they are waiting for their assessment.
If musculoskeletal pain is not well controlled with an appropriate dose of NSAIDs or if anti-inflammatory therapy was contraindicated for other systemic affection, other strategies may be considered. The American Pain Society 2002 guidelines recommended the use of tramadol plus acetaminophen therapy when NSAID are insufficient. The combination of tramadol and acetaminophen has been shown pharmacologically to have a faster onset of action (17 minutes versus 51 minutes for tramadol alone) and a longer duration of action (five hours versus two hours for tramadol and two hours for acetaminophen) than either agent alone9.
Some patients may still not have adequate pain control using NSAIDs or combination therapy, or may have co-morbid conditions precluding the use of such agents10. Opioid analgesics may offer significant relief for these patients. Initial dosing of narcotic agents should be preferentially lower than that given to a younger patient, with longer dose intervals and slower dose increment increases.
Effective treatment of chronic joint pain may be enhanced by sustained delivery of opioids from a transdermal system. Buprenorphine is one of the good options available especially in its low doses (5µg/h). The advantage of buprenorphine is that it is available in the form of skin patches administered every seventh day. However, careful physician follow-up and assessment of side effects is essential with opioid therapy, with particular attention to more common and problematic toxicities such as constipation, excessive sedation and confusion. Given the propensity of these drugs to cause constipation, timely and prophylactic use of laxatives is often needed with the initiation of a narcotic agent11.
Disease Modifying AntiRheumatic Drug Therapy (DMARDs)
Over the past decade there have been significant changes in the medical management of RA. It started with the increasing use of DMARDs especially early in the RA disease course, then a new era in the management started with the introduction of biologic therapy. In fact, the introduction of the novel biologic response modifiers or targeted therapy has set new standards in the treatment of all rheumatic diseases. These agents not only modify disease (hence the name) in terms of influencing its signs and symptoms, achieving high responder rates, and retarding radiographic progression12-17, but have also made it possible to translate recent pathogenetic insights into clinical practice18,19.
The main biologics approved for use are the Tumor Necrosis Factor-alpha (TNF-ƒ) inhibiting agents (infliximab, etanercept and adalimumab) and interleukin-1 receptor antagonist (anakinra). They were marketed for RA patients as clinical studies showed that these agents have been efficacious particularly for patients who failed to show improvement with prior DMARD therapy. Interestingly, recent studies demonstrated similar positive efficacy in other rheumatic diseases raising the question of the role of TNF-ƒ in the pathogenesis of rheumatic diseases20.
Although these agents are being used more widely in younger patients with early onset disease, where they have been shown to slow disease progression and limit joint damage, in elderly patients the benefits versus risks should be weighed carefully on individual basis. Adverse effects related to the biologic therapy include severe infections especially tuberculosis, as well as sepsis, congestive heart failure and malignancies particularly lymphomas21-23.
Because many older RA patients are Purified Protein Derivative (PPD) positive, have known malignancies in remission (such as breast, prostate or melanoma), may have underlying cardiac dysfunction as well as chronic sources of infection (e.g. venous stasis ulcers, recurrent urinary tract infections), these agent might be potentially more hazardous in this population than in younger RA patients. Table 1 shows doses, route of administration and recommendations for using the anti-rheumatoid agents in the elderly patient with RA.
Mono-articular synovitis or pain can be treated with intra-articular steroid injections. Although this does not modify disease course, it can be an ameliorating measure and provide symptom relief for a period of time, with fewer side effects than the systemic therapy. It is generally not advisable to do more than four joint injections per joint per year, because of concern regarding accelerated osteoarthritis and corticosteroid-induced cartilage loss. However, it must be added here, that the proper management of the inflamed joints is through readjustment of the DMARD or biologic therapy dose and not in re-injecting it without controlling the disease activity.
When medical therapy has failed and a patient is still experiencing intolerant pain or severe disability, surgical options should be considered. Orthopedic surgeons and their patients have experienced significantly successful outcomes with joint replacement surgery24. One study evaluating a group of 80-year old men and women undergoing knee replacement surgery found 83 per cent to be ambulating pain-free five years after the procedure.
Nevertheless, surgery is not without risks. Three per cent of patients over 80 years had prolonged rehabilitation stays following surgery, most often related to delirium and cognitive impairment.
Patients must be selected carefully for surgery based on their co-morbid medical conditions as well as their expected functional level following the intervention. Also it should be clear when the patient should be referred for surgery. Late referral when the joint is severely affected is usually associated with muscle weakness and wasting. This would have negative impact on the outcome of surgery.
As in other areas of geriatric medicine, providing good care for the older patients with RA often requires a careful multi-disciplinary approach with emphasis placed on adequate treatment for comorbid conditions, limitation of extraneous and superfluous medications to diminish polypharmacy and lastly vigilant attention to adverse drug reactions and drug-drug interactions.
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