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[O276]Onset Of Rheumatoid Arthritis

by Nathan Wei, Nat

Rheumatoid arthritis (RA) affects 2% of those 60 years old and older and is generally more common among women. When RA presents in patients past the age of 60, it may present with an acute onset, with significant inflammatory symptoms, and predominant upper extremity involvement, eg. shoulders. Inflammatory markers in the blood such as the erythrocyte sedimentation rate (ESR) may be greatly elevated.

Diagnostic testing is similar to that for diagnosing RA in younger individuals. Acute phase reactants for inflammation such as the ESR and CRP will invariably be abnormal. Serologic testing for rheumatoid factor and anti-cyclic citrullinated protein (anti-CCP) are helpful.

The diagnostic imaging procedure of choice is probably magnetic resonance imaging (MRI), although diagnostic ultrasound may be useful.

Other disease processes that need to be excluded include: calcium pyrophosphate deposition disease (CPPD), osteoarthritis, gout, polymyalgia rheumatica (PMR), arthritis associated with infections such as hepatitis B,C , and immunodeficiency virus. Tuberculosis and fungal infections such as histoplasmosis, coccidiomycosis, and blastomycosis can also present with inflammation of many joints.

Endocrine disorders such as diabetes and Cushing's disease may also present with diagnostic challenges.

Malignancy is another consideration. An inflammatory arthritis affecting many joints in a patient over the age of 60 should lead the physician to working up the patient for an underlying malignancy. Also, certain malignancies such as lymphoma are increased in incidence in patients with rheumatoid arthritis.

The treatment of EORA presents special challenges. First, a patient with RA past the age of 60 probably has other medical conditions. Second, they are probably on multiple medications. The diagnosis may be confounded by the fact the both ESR and rheumatoid factor can be elevated in older patients who don't have RA. Finally, treatment with medications needs to be tempered with the knowledge that potential side-effects may be increased in this population where drug metabolism is less certain than that of younger patients.

Nonetheless, the approach to therapy for patients with EORA is not substantially different from the treatment strategies employed for younger patients.

Non-steroidal anti-inflammatory drugs (NSAIDS) are often used early on in younger patients. However, in older patients who may develop kidney and liver toxicity with these agents, the use of NSAIDS is probably a strategy that has to be watched closely.

Low dose prednisone (5-10mgs) given as a single morning dose provides symptomatic relief and can serve as a “bridge” until the effects of second line agents begin. The potential complications of long-term prednisone therapy such as osteoporosis and cataracts, among others, will be more of a concern than for younger patients.

Second line agents consist of two groups. They are the disease-modifying anti-rheumatic drugs (DMARDS) and the biologic drugs.

Disease-modifying drugs such as methotrexate, hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine), and leflunomide (Arava) are all potentially useful. Obviously, with older patients, potential toxicities and drug interactions need to be monitored for carefully.

Biologic therapies can also be used for patients with EORA. TNF inhibitors such as etanercept (Enbrel), adalimumab (Humira), infliximab (Remicade, and the two newer agents golimumab (Simponi), and certolizumab (Cimzia) are all effective and well tolerated in the older population of patients with rheumatoid arthritis.

Second line biologics such as rituximab (Rituxan) and abatacept (Orencia) have also been used in patients with EORA with results comparable to that for younger patients.

Advancing age should not, by itself, be a contraindication to the use of biologic therapies. The aim for older patients, as it is with younger patients, is to establish remission. This may be even more important in older patients since independence is cherished more. Finally, since cardiovascular events are an established complication of rheumatoid arthritis and are also more common in older adults, every effort should be instituted to establish and maintain remission.

However, as with all therapies there are potential downsides. One of the risks that has been written extensively about is infections, particularly with TNF-α inhibitors. Examples of these drugs include Enbrel, Humira, and Remicade.

A recent study supports the notion that infections are not only increased in incidence but also are responsible for more hospitalizations in patients with rheumatoid arthritis.

Among patients with rheumatoid arthritis, treatment with tumor necrosis factor (TNF) antagonists is associated with a "small to moderate" increase in risk of hospitalization with infection. (Askling J, et al. Ann Rheum Dis 2007;66:1339-1344).

The authors state, "These findings add to the emerging evidence to suggest that anti-TNF treatment is indeed associated with an increased risk of infections," and they add, "since? closer monitoring for infections may be difficult to achieve in clinical practice, an increased awareness and increased patient information of this potential side effect of treatment may be indicated."

The investigators studied a total of 45,000 RA patients obtained from the Swedish Biologics Register and other national Swedish registers to determine the outcome, relative risks, and predictors of hospitalization with an infection in patients with rheumatoid arthritis.

They found that treatment with a first TNF inhibitor was associated with a significant 43% increased risk of hospitalization with infection during the first year of treatment. Infection risk during the second year and thereafter was not significantly increased.

The relative risk for infection was two times higher during treatment with a second TNF inhibitor, the researchers note.

Using additional data, other risk factors identified as being significant predictors for infection with TNF inhibitor treatment were older age, higher Health Assessment Questionnaire (HAQ) score, and disease-modifying anti-rheumatic drug (DMARD) treatment other than methotrexate.

When infections were assessed by type, only respiratory infection showed a slightly significant increase in relative risk in association with TNF antagonist treatment.

It is unclear so far as to whether the risk is due to one of the TNF inhibitor drugs more than another.

These findings, as well as other observational trials, mirror what was seen in the clinical trials that led to approval by the FDA for the treatment of RA.

Patients who are prospective candidates for this type of treatment need to be warned about this potential side effect.

In addition, they should be monitored carefully. In the future, it may be possible to identify high risk patients ahead of time so that other therapies might be offered instead of anti-TNF drugs.

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Nathan Wei has sinced written about articles on various topics from Arthritis Pain, Health and Arthritis Signs. Nathan Wei, MD FACP FACR is a nationally known board-certified rheumatologist. For more info: an. Nathan Wei's top article generates over 550000 views. to your Favourites.