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With the introduction of biologic therapies for inflammatory bowel disease, significant questions have arisen regarding their best optimization. Although initial recommendations were to combine immunosuppressives with biologics to reduce immunogenicity, trials with 3 different anti-tumor necrosis factor agents (infliximab, adalimumab, and certolizumab) and a humanized monoclonal antibody that targets alpha-4 integrins (natalizumab) have failed to demonstrate the clinical superiority of combination therapy when high-dose induction and scheduled maintenance therapy was prescribed for up to 1 year. However, immunosuppressive agents should be considered with episodic biologic therapy to decrease immunogenicity and secondary loss of response. The issue of whether induction with biologics and maintenance therapy with immunosuppressives as monotherapy is as safe and effective as induction and maintenance with biologics alone still remains to be addressed. Further, with the use of concomitant immunosuppressives and biologics, evolving data raise concerns for an increase in adverse events, including opportunistic infections, neurological disorders, and cancer. Specific therapeutic decisions need to be individualized and the clinician must help the patient weigh quality-of-life issues with readiness to assume possible risks.

Diarrhea continues to be a prevalent symptom in patients with inflammatory bowel disease (IBD), requiring a wide differential diagnosis to define the pathophysiologic mechanisms in individual patients. It is essential that physicians properly evaluate complaints of diarrhea by assessing both patient symptoms and potential physiologic impacts on fluid and electrolyte status. Underlying mechanisms of diarrhea with IBD are the location, extent, and severity of inflammation; malabsorption; altered motility; and iatrogenic causes such as medications, diet, and antibiotic-associated colitis (eg, Clostridium difficile). When treating diarrhea, physicians need to control inflammatory activity using appropriate treatment algorithms. Therapies include aminosalicylates, corticosteroids, immune modifiers, and, most recently, biologic treatment. Other medications, including loperamide, diphenoxylate, codeine sulfate, and tinctures of opium, slow motility and increase the absorption of fluids and nutrients. For iatrogenic issues, medications that cause diarrhea should be withdrawn and individual diets modified. Not all diarrheas in the IBD patient are the same; therefore, it is essential to tailor therapies according to presumed etiologies. Antidiarrheal agents are not recommended in extremely ill patients and those with known hypersensitivity or evidence of obstruction or colonic dilation, fever, or abdominal tenderness. Concomitant use of loperamide with diphenoxylate and atropine should be avoided in early pregnancy.