A 35-year-old woman comes to the physician with pain and stiffness of her wrists and hand joints for the last several months. Her morning stiffness lasts for more than an hour. She also complains of joint swelling. Her past medical history is significant only for a similar episode a year ago, which resolved with over-the-counter ibuprofen. Joint examination shows mild redness, warmth, swelling, and tenderness in the proximal interphalangeal and metacarpophalangeal joints and wrists. X-rays show periarticular osteopenia and erosions of the proximal interphalangeal and metacarpophalangeal joints. The patient began taking indomethacin, which provides good relief, but symptoms recur if she skips a dose. Which of the following is the most appropriate next step in management of this patient?
This patient's presentation is consistent with moderate-to-severe rheumatoid arthritis (RA). RA is a chronic, systemic inflammatory disorder with progressive erosion of the bone and cartilage and significant joint destruction and deformity. Patients typically present with joint findings (eg, pain, stiffness, swelling), morning stiffness, involvement of proximal interphalangeal and metacarpophalangeal joints, and radiographic evidence of erosions and/or periarticular osteopenia. Treatment goals in RA are to induce and maintain early remission, control synovitis, and prevent progression of joint damage.
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All patients diagnosed with RA should be started on disease-modifying antirheumatic agents (DMARDs) as soon as possible as joint damage begins early in its course (Choice G). Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors (eg, celecoxib) are adjunctive therapies for symptomatic relief but do not reduce disease progression. Glucocorticoids can also relieve symptoms and short-term radiographic progression but are also not effective in preventing eventual joint destruction. In fact, they can result in generalized bone loss (ie, osteoporosis).
DMARDs include nonbiologic agents (eg, methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, azathioprine) and biologic agents (eg, etanercept, infliximab, adalimumab, tocilizumab, rituximab). Methotrexate is the preferred initial DMARD in patients with moderately to severely active RA due to its efficacy and long-term safety profile. Patients should be tested for hepatitis B and C before starting therapy. Methotrexate should not be used in patients who are pregnant or are planning to become pregnant in the near future and those with severe renal insufficiency, liver disease, or excessive alcohol intake. Patients who do not respond after 6 months may require biologic DMARDs such as tumor necrosis factor-alpha inhibitors (eg, etanercept, infliximab) as step-up therapy (Choices C and E).
(Choice A) Azathioprine is an immunosuppressive agent that has been used to treat RA. However, it is not as efficacious as other DMARDs and is associated with significant hematologic and gastrointestinal toxicity.
(Choices B and D) This patient notes improvement with indomethacin and does not require additional symptomatic treatment with celecoxib or glucocorticoids.
Educational objective:
All rheumatoid arthritis (RA) patients should receive disease-modifying antirheumatic drugs (DMARDs) as early as possible in the disease course. Methotrexate is the initial DMARD of choice in most patients with active RA. Nonsteroidal anti-inflammatory drugs or glucocorticoids should be used for initial temporary symptomatic relief while awaiting response to DMARD therapy.