More biologics for patients with Crohn's disease

Be aware that biologics are typically given every 2 to 8 weeks for Crohn's, so delaying a dose during a hospital stay is likely okay....
Mahitab Hany, BS Pharm, PGDipClinPharm, PGDipClinNutrition

AS A HOSPITAL PHARMACIST, you will see more biologics on home medication lists for patients with Crohn's disease and some older medications falling out of favor. Be familiar with common treatments and optimize Crohn's maintenance therapy when patients are admitted for other reasons.

         BIOLOGICS. A "top-down" treatment approach includes earlier use of biologics, such as the TNF-alpha blockers; infliximab (Remicade), adalimumab (Humira), certolizumab (Cimzia), etc. These can lead to faster and longer remission in some high-risk patients (see Table 1 for doses). Be aware that biologics are typically given every 2 to 8 weeks for Crohn's, so delaying a dose during a hospital stay is likely okay. Consider a drug-induced cause when a patient taking a TNF-alpha blocker is admitted with an opportunistic infection or heart failure.

Table (1). Biologics for Crohn’s Disease
Drug Dosing (adult) Comments
Adalimumab or certolizumab can be used first-line for moderate or severe disease. Efficacy can be seen within two weeks. Before starting, screen for latent infection such as tuberculosis, hepatitis B, histoplasmosis, and blastomycosis. Hold in the event of serious infection. Vaccinate, ideally before treatment, against hepatitis A and B, pneumonia, human papilloma virus, flu, varicella, and zoster, but do not use live vaccines in patients using immunomodulatory or biologic therapy. Use caution in heart failure (Canadian labeling contraindicates use in NYHA Class III or IV heart failure); if history of recurrent bacterial or viral infection; or in women who are pregnant, lactating, or planning pregnancy. Combination therapy with infliximab and thiopurines (azathioprine or 6-mercaptopurine) is more effective than monotherapy in thiopurine-naive patients. Combining adalimumab or certolizumab with an immunomodulator is not well studied, but is likely to be beneficial and reduce anti-drug antibody formation.
Adalimumab (Humira)
Induction: 160 mg (single dose or divided [80 mg on days 1 and 2]), then 80 mg two weeks later.

Maintenance: 40 mg every-other-week.		 Given subcutaneously.

The most common adverse effect is mild to moderate injection site reactions (e.g., redness, irritation) in < 10% of patients.
Certolizumab (Cimzia)
Induction: 400 mg at weeks 0, 2, and 4.

If patient responds (e.g., reduction in CDAIa score of ≥ 100 points) by 8 weeks, give 400 mg every four weeks.		 Given subcutaneously.

The most common adverse effect is mild to moderate injection site reactions (e.g., redness, irritation) in < 10% of patients.
Infliximab (Remicade)
Induction: 5 mg/kg at weeks 0, 2, and 6.

If patient responds (e.g., reduction in CDAIa score of ≥70 points) by 14 weeks, give 5 mg/kg every eight weeks. Can increase further to 10 mg/kg if patient loses response.
 Given as an infusion; not for home use.

Can be given intermittently to address symptoms (5 mg/kg), but intermittent therapy poses a higher risk of antibody development.

May be the most effective TNF-alpha blocker for fulminant disease.

Biosimilars can be used, but there is insufficient information on the safety and efficacy of switching among infliximab products.

May cause acute or delayed infusion reactions. Infusion center must be prepared to treat serious reactions (have epinephrine, etc on hand).
    • Delayed reactions occur 24 hours to 14 days post-infusion and may include arthralgia, myalgia, fever, malaise, hives, angioedema, lymphadenopathy, or itching, or serious serum sickness reactions.
    • Consider cautious use of adalimumab or certolizumab for patients with a severe reaction.

IMMUNPMODULATORS. Azathioprine 1.5–2.5 mg/kg/day or mercaptopurine 0.75–1.5 mg/kg/day may be used in active CD as adjunctive therapy and as a steroid sparing agent. Methotrexate IM 25 mg weekly for up to 16 weeks followed by 15 mg weekly is effective for chronic active disease.

         Don't be surprised to see a biologic PLUS an immunomodulator (azathioprine, methotrexate, etc). The combo may be more effective than either one alone. Usually continue immunomodulators during a hospital stay. Double-check that methotrexate doses are scheduled weekly not daily. Think about lowering the dose or stopping these medications if you see bone marrow suppression or elevated liver enzymes or a severe infection. Stop azathioprine if you suspect it's causing acute pancreatitis.

5-AMINOSALICYLATES (5-ASA). Expect fewer Crohn's patients to use sulfasalazine 4 g daily or mesalamine > 2 g/day. The latest evidence suggests 5-ASAs aren't much more effective than placebo for Crohn's.

Help prevent flares in Crohn's patients by emphasizing smoking cessation, if indicated. And try to avoid NSAIDs, since they may exacerbate GI symptoms. For CD, nutrition should be considered an integral component of the management of all patients. Nutritional status (including body mass index) is best assessed. Monitor height and weight in children and adolescents. Specific attention should be paid to vitamin B12 status, especially after ileal resection.

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