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ACP develops three different types of clinical recommendations:

Clinical Practice Guidelines, Clinical Guidance Statements, and Best Practice Advice. ACP's goal is to provide clinicians with recommendations based on the best available evidence; to inform clinicians of when there is no evidence; and finally, to help clinicians deliver the best health care possible.

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Our goal is to help clinicians deliver the best health care possible.

The American College of Physicians (ACP) established its evidence-based clinical practice guidelines program in 1981. The ACP clinical practice guidelines and guidance statements follow a multistep development process that includes a systematic review of the evidence, deliberation of the evidence by the committee, summary recommendations, and evidence and recommendation grading.

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A 36-year-old woman is evaluated for a 2-month history of pain and swelling in the fingers and wrists. She reports increased fatigue and has stopped going to the gym. She takes over-the-counter ibuprofen, which provides temporary and incomplete relief.

On physical examination, temperature is 36.7°C (98.0°F), blood pressure is 130/70 mm/Hg, and pulse rate is 87/min. Examination of the joints shows swelling of the second, third, and fifth proximal interphalangeal joints and wrists bilaterally. There is no heart murmur, and the lungs are clear. There is no rash.

Laboratory studies:

Erythrocyte sedimentation rate

48 mm/h


10.8 g/dL (108 g/L)

C-reactive protein

17.8 mg/dL (178 mg/L)

Rheumatoid factor

260 U/mL (260 kU/L)

Anti-cyclic citrullinated peptide antibodies


Radiographs of the hands and wrists show periarticular osteopenia at the carpus bilaterally.


Which of the following is the most appropriate treatment?

The most appropriate treatment for this patient diagnosed with rheumatoid arthritis (RA) is methotrexate. This nonbiologic disease-modifying antirheumatic drug remains the first choice for the treatment of RA because of its efficacy, ease of use, availability, cost, and low incidence of side effects. Using methotrexate initially after making the diagnosis of RA is the standard of care worldwide. It is effective for most patients in reducing pain and swelling of the joints and in slowing, and sometimes halting, the progression of destructive bony changes that can result from uncontrolled disease. These changes, including joint-space narrowing and erosions, can be seen on plain radiographs, and, if present at the time of diagnosis, can help confirm the diagnosis.

Although tumor necrosis factor (TNF)-α inhibitors such as etanercept are approved for use in RA as initial treatment and as monotherapy, their cost is substantially greater than that of methotrexate. Furthermore, TNF-α inhibitors have generally been found to have greater efficacy when used in combination with methotrexate. Thus, in the absence of a contraindication to the use of methotrexate, a TNF-α inhibitor should not be the first choice in therapy.

Leflunomide is approved for use in the treatment of RA, either as monotherapy or in combination with methotrexate. However, it is used primarily in patients who do not respond adequately to methotrexate and who are not eligible for other treatment approaches. It is not generally the first choice for treatment of women of childbearing age because it requires a cumbersome procedure to accelerate drug elimination if the patient were to become pregnant because it is contraindicated in pregnancy.

Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes B cells and is approved to treat RA in patients already taking methotrexate who have had an inadequate response to TNF-α inhibitors. It also requires intravenous administration and is costly. Rituximab is therefore not appropriate for this patient.

Tofacitinib is a JAK kinase inhibitor that decreases signalling by a number of cytokine and growth factor receptors and is reserved for those who have had an inadequate response to methotrexate. Because of potential side effects, it is not an appropriate treatment choice for initial therapy in this patient.

Key Point

  • The nonbiologic disease-modifying antirheumatic drug methotrexate is the initial therapy of choice for patients diagnosed with rheumatoid arthritis
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