Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 22-year-old woman is evaluated for a flare of Crohn disease. A colonoscopy performed 6 months ago showed moderate, patchy, left-sided colitis extending from the descending colon to the splenic flexure. She responded to therapy with prednisone but declined maintenance therapy in advance of conceiving. She is now 12 weeks pregnant and for the past 2 weeks has experienced bloody diarrhea and left-sided abdominal pain.
On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 110/66 mm Hg, and pulse rate is 76/min. Abdominal examination reveals left-sided abdominal tenderness without guarding or rebound.
Flexible sigmoidoscopy shows recurrent left-sided patchy colitis, and stool studies are negative for Clostridium difficile infection.
Which of the following is the most appropriate treatment?
A. Certolizumab
B. Ciprofloxacin and metronidazole
C. Controlled ileal-release budesonide
D. Mesalamine
E. Methotrexate
MKSAP Answer and Critique
The correct answer is A. Certolizumab.
The most appropriate treatment is certolizumab. The previously used treatment approach for Crohn disease (CD) was to 1) initiate therapy with 5-aminosalicylate drugs such as mesalamine at diagnosis; 2) begin thiopurine therapy with azathioprine or 6-mercaptopurine if a patient requires repeated courses of glucocorticoids; and 3) begin therapy with anti–tumor necrosis factor (anti-TNF) agents if these other therapies are unsuccessful. This paradigm has been challenged by newer studies showing that 5-aminosalicylates have only minimal, if any, efficacy in CD, and the success of treatment is significantly higher when anti-TNF therapy is begun alone or in combination with thiopurines earlier in the disease course. Many experts have abandoned the use of 5-aminosalicylates entirely for CD except perhaps for those with mild Crohn colitis. The decision to use thiopurine or anti-TNF monotherapy versus combination therapy is based on an individual patient’s severity of symptoms and risk factors for developing complications of their disease balanced against the potential side effects of these treatments. This patient with new-onset CD is in her first trimester of pregnancy. Treatment with an anti-TNF agent is effective for induction and maintenance of remission in CD and is generally considered to be safe during pregnancy (FDA pregnancy category B). The three anti-TNF agents approved for CD are infliximab, adalimumab, and certolizumab. Because certolizumab is pegylated, it should have very little, if any, placental transfer and therefore is favored by some clinicians in a pregnant patient over the other two agents. Although endoscopic procedures are generally avoided in pregnant patients unless absolutely necessary, flexible sigmoidoscopy is safer than colonoscopy, and in this patient it was useful to confirm that her symptoms are due to active CD before committing her to expensive immunosuppressive medications.
Antibiotics are generally not recommended for induction of remission in CD because no particular class of drug can be endorsed based on available data. Furthermore, ciprofloxacin (pregnancy category C) should be used in pregnancy only if the potential benefits outweigh the risk to the fetus. Metronidazole is a pregnancy category B drug.
Controlled ileal-release budesonide is effective for ileocolonic CD, but it would not be effective in this patient with left-sided colitis. In addition, it is classified as category C for use during pregnancy.
Mesalamine may be used to treat ulcerative colitis, but it is not effective in most patients with CD.
Methotrexate may be effective for inducing and maintaining remission in CD, but it is contraindicated during pregnancy. Methotrexate is a classified as category X for use in pregnancy because it may cause fetal death and/or congenital abnormalities.
Key Point
- Treatment with an anti–tumor necrosis factor agent is effective for induction and maintenance of remission in Crohn disease and is generally considered to be safe during pregnancy (FDA pregnancy category B).
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