Key Clinical Updates in Inflammatory Bowel Disease
Clinical remission and endoscopic improvement at 1 year were seen in significantly more patients with ulcerative colitis treated with vedolizumab than with adalimumab.
In light of a 2019 FDA black box warning, tofacitinib is restricted to second-line therapy in patients with ulcerative colitis who have not responded or have lost response to anti-TNF therapy.
The term “inflammatory bowel disease” includes ulcerative colitis and Crohn disease. In the United States, there are approximately 1.6 million people with inflammatory bowel disease with adjusted annual incidences of 12.2 cases/100,000 and 10.7 cases/100,000 person-years for ulcerative colitis and Crohn disease, respectively. Ulcerative colitis is a chronic, recurrent disease characterized by diffuse mucosal inflammation involving only the colon. Ulcerative colitis invariably involves the rectum and may extend proximally in a continuous fashion to involve part or all of the colon. Crohn disease is a chronic, recurrent disease characterized by patchy transmural inflammation involving any segment of the gastrointestinal tract from the mouth to the anus.
Crohn disease and ulcerative colitis may be associated in 50% of patients with a number of extraintestinal manifestations, including oral ulcers, oligoarticular or polyarticular nondeforming peripheral arthritis, spondylitis or sacroiliitis, episcleritis or uveitis, erythema nodosum, pyoderma gangrenosum, hepatitis and sclerosing cholangitis, and thromboembolic events.
Although ulcerative colitis and Crohn disease appear to be distinct entities, several pharmacologic agents are used to treat both. Despite extensive research, there are still no specific therapies for these diseases. The mainstays of therapy are 5-aminosalicylic acid derivatives, corticosteroids, immunomodulating agents (such as mercaptopurine or azathioprine and methotrexate), and biologic agents.
A. 5-Aminosalicylic Acid (5-ASA)
5-ASA is a topically active agent that has a variety of anti-inflammatory effects. It is used in the active treatment of ulcerative colitis and Crohn disease and during disease inactivity to maintain remission. It is readily absorbed from the small intestine but demonstrates minimal colonic absorption. A number of oral and topical compounds have been designed to target delivery of 5-ASA to the colon or small intestine while minimizing absorption. Commonly used formulations of 5-ASA are sulfasalazine, mesalamine, and azo compounds. Side effects of these compounds are uncommon but include nausea, rash, diarrhea, pancreatitis, and acute interstitial nephritis.
1. Oral mesalamine agents
These 5-ASA agents are coated in various pH-sensitive resins (Asacol, Apriso, and Lialda) or packaged in timed-release capsules (Pentasa). Pentasa releases 5-ASA slowly throughout the small intestine and colon. Asacol, Apriso, and Lialda tablets dissolve at pH 6.0–7.0, releasing 5-ASA in the terminal small bowel and proximal colon. Lialda has a multi-matrix system that gradually releases 5-ASA throughout the colon.
Sulfasalazine, balsalazide, and olsalazine contain 5-ASA linked by an azo bond that requires cleavage by colonic bacterial azoreductases to release 5-ASA. Absorption of these drugs ...