View the Table: Safety of Drugs for IBD in Pregnancy

Ulcerative colitis (UC) and Crohn's disease (CD), referred to collectively as inflammatory bowel disease (IBD), are chronic immune-mediated inflammatory conditions. Guidelines for treatment of UC and CD have been updated in recent years

View the Table: Some Drugs for Inflammatory Bowel Disease

The oral sphingosine 1-phosphate (S1P) receptor modulator ozanimod (Zeposia – Bristol Myers Squibb) has been approved by the FDA for treatment of adults with moderately to severely active ulcerative colitis. It is the first S1P receptor modulator to be approved for treatment of ulcerative colitis. Ozanimod was approved in March 2020 for use in adults with relapsing forms of multiple sclerosis.

Management of both ulcerative colitis (UC) and Crohn's disease (CD) is based on disease severity. Disease location (proctitis, left-sided colitis, or extensive colitis) also plays a role in drug selection. Some drugs for induction and maintenance of remission of inflammatory bowel disease (IBD) are listed in Table 1.

View Expanded Table: Some Drugs for Inflammatory Bowel Disease

Aminosalicylates are effective for induction and maintenance of remission in mild to moderate ulcerative colitis. They are not recommended for treatment of Crohn's disease.

FORMULATIONS — Oral mesalamine is rapidly absorbed in the small intestine and most of the drug does not reach the colon. Pentasa releases mesalamine gradually throughout the gastrointestinal tract. Delzicol, Asacol HD, Lialda, and Apriso delay the release of the drug until it reaches the distal ileum and colon. Sulfasalazine (Azulfidine, and generics), balsalazide (Colazal, and others), and olsalazine (Dipentum) are prodrugs; mesalamine is azo-bonded to a second moiety and released in the colon following bacterial cleavage of the bond. Mesalamine is also available as an enema (Rowasa, and generics) and as a rectal suppository (Canasa).

Inflammatory bowel disease (IBD) is generally classified as either Crohn’s disease (CD) or ulcerative colitis (UC). More detailed guidelines on their treatment are available from the American College of Gastroenterology.

Inflammatory bowel disease (IBD) is either Crohn's disease or ulcerative colitis. Drug selection is guided by disease type (Crohn's versus ulcerative colitis), severity and location and whether the goal is induction or maintenance of remission. Table 1 on page 66 lists the drugs used to treat IBD with their formulations and cost. Table 2 on page 68 lists the drugs of choice and their doses for different indications. Table 3 on page 71 lists the drugs' adverse effects and recommendations for monitoring. More detailed guidelines are available from the American College of Gastroenterology.

Apriso (Salix) is a new formulation of mesalamine (5-aminosalicylic acid; 5-ASA) approved by the FDA for maintenance of remission in mild to moderate ulcerative colitis (UC). Mesalamine is a locally acting antiinflammatory agent that is widely used both to maintain and induce remission in inflammatory bowel disease. Various mesalamine formulations have been developed to target drug delivery to areas of the small intestine and colon. Most of these agents require frequent dosing and have a high pill burden. The newest products - Lialda, introduced in 2007,1 and now Apriso - can be dosed once daily.

The May 5, 2008 article (Med Lett Drugs Ther 2008; 50:34) on the approval of natalizumab (Tysabri) for treatment of Crohn's disease in the "Adverse Effects" section on page 35 included the statement: "post-marketing hepatotoxicity, sometimes fatal or requiring liver transplantation, has occurred." Actually, no fatal hepatotoxicity or liver transplantation has been reported to date. The FDA warning about post-marketing hepatotoxicity with Tysabri that was the basis for our statement said: "The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to [emphasis added] death or the need for a liver transplant in some patients." Also, in the last sentence of the Conclusion, we should have said: "Because of the risk of serious hepatic toxicity and the rare but even more serious risk of developing progressive multifocal leukoencephalopathy, it should be used only in patients who have not responded to other drugs, including a TNF inhibitor." The italicized words should be substituted for "it is FDA-approved for use."

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Natalizumab (Tysabri - Elan and Biogen) is a monoclonal antibody approved for induction and maintenance treatment of moderate to severe Crohn's disease (CD) refractory to conventional therapies and inhibitors of tumor necrosis factor (TNF). Initially approved in 2004 for the treatment of multiple sclerosis (MS), natalizumab was temporarily withdrawn from the market after 3 patients developed progressive multifocal leukoencephalopathy (PML). It is now available for treatment of both MS and CD through a restricted distribution program.

A once-daily oral formulation of mesalamine (Lialda - Shire) was recently approved by the FDA for induction of remission in patients with mild to moderate ulcerative colitis.

Budesonide (Entocort EC — AstraZeneca), a locally active glucocorticosteriod widely used for inhalation treatment of allergic rhinitis and asthma (Medical Letter 2000; 42:19), has been approved for oral treatment of mild to moderate active Crohn's disease involving the ileum and/or ascending colon. Both oral budesonide and budesonide enemas have been available for years in Europe and Canada for treatment of inflammatory bowel disease.

Balsalazide disodium (Colazal), a prodrug of mesalamine, was marketed in the US this year for oral treatment of mildly to moderately active ulcerative colitis. Oral formulations of mesalamine have been available in the US for nine years for treatment and maintenance of remissions and olsalazine, which is a dimer of mesalamine, is marketed for maintenance of remissions but not for treatment. Balsalazide has been available in Europe for four years.

An oral formulation of mesalamine (5-aminosalicylic acid, 5-ASA, Asacol - Proctor & Gamble), was recently approved by the US Food and Drug Administration (FDA) for treatment of mildly to moderately active ulcerative colitis; it has not been approved for maintenance of remissions. Olsalazine (Dipentum), a similar drug (Medical Letter, 32:105, 1990), is approved for maintenance of remissions but not for treatment.