A 55-year-old woman comes for evaluation of persistent morning stiffness. She was diagnosed with rheumatoid arthritis 4 months ago and was prescribed methotrexate. The patient currently takes the maximum tolerated dose, along with folic acid and as-needed naproxen. Vital signs are normal. On examination, swelling, tenderness, and pain on range of motion are found at the metacarpophalangeal and proximal interphalangeal joints and wrists bilaterally. Treatment with etanercept is considered. Which of the following tests should be performed before beginning treatment with this agent?
Tumor necrosis factor-alpha (TNF-α) inhibitors are large-molecule anti-inflammatory agents ("biologics") commonly used to treat moderate to severe rheumatoid arthritis, particularly in patients who have failed methotrexate therapy. Etanercept is a fusion protein with domains derived from the Fc portion of IgG1 and TNF receptor 2. It functions as a decoy receptor for TNF-α. Other TNF-α inhibitors are anti-TNF monoclonal antibodies (eg, infliximab, adalimumab).
Inhibition of TNF-α leads to impaired cell-mediated immunity. In particular, TNF-α is necessary for effective sequestration of mycobacteria within granulomas. As a result, TNF-α inhibitors promote reactivation of latent tuberculosis and can increase the risk of disseminated disease. All patients being considered for TNF-α inhibitor therapy should have a baseline tuberculin skin test or interferon-gamma release assay to screen for latent tuberculosis. TNF-α inhibitors also increase susceptibility to other infectious agents, including fungi and atypical mycobacteria, and should not be used in any patient with an underlying infection.
(Choice A) CT is effective in diagnosing a variety of infections of the central nervous system, including disseminated tuberculosis. However, a baseline CT scan is not needed in rheumatoid arthritis in the absence of suspicious symptoms.
(Choice B) Baseline assessment of left ventricular function with echocardiogram or radionuclide ventriculography is recommended prior to treatment with anthracycline antineoplastic drugs (eg, doxorubicin).
(Choice C) Patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are at increased risk for peptic ulcer. Fecal occult blood testing should be performed in patients taking NSAIDs whenever there is a clinical suspicion of gastrointestinal bleeding.
(Choice D) Pulmonary function tests may be important in patients taking medications known to cause pulmonary fibrosis, such as amiodarone. Methotrexate can cause both lung and liver toxicity, and a baseline chest x-ray and liver function tests are recommended.
(Choice F) Irreversible retinal damage can occur with long-term use of hydroxychloroquine. Patients starting hydroxychloroquine should have baseline and regular follow-up ophthalmologic examinations.
Educational objective:
Tumor necrosis factor-alpha (TNF-α) inhibitors impair cell-mediated immunity. All patients beginning treatment with TNF-α inhibitors should be evaluated for latent tuberculosis.