Newer Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease
Daniel C. Baumgart et al.
Crohn’s disease and ulcerative colitis, together referred to as inflammatory bowel disease (IBD), are chronic systemic inflammatory disorders.1 These conditions target primarily the gastrointestinal tract but can affect many organ systems through extraintestinal manifestations (e.g., peripheral and axial arthritis, episcleritis, primary sclerosing cholangitis, or pyoderma gangrenosum).2 Ulcerative colitis is restricted to the colon, whereas Crohn’s disease is characterized by involvement of the gastrointestinal tract from mouth to anus in a discontinuous fashion, with the development of strictures, abscesses, or fistulas that penetrate neighboring organs or the perianal skin. The initial clinical presentation depends on the extent and activity of the disease and may include abdominal pain, diarrhea (frequently nocturnal in addition to diurnal) with passage of blood and mucus, fever, and clinical signs of bowel obstruction, as well as anemia and elevated measures of laboratory markers of inflammation. With no cure, an increased risk of various digestive and other malignant processes associated with uncontrolled inflammation,3 and possible involvement of virtually the entire human body, IBD requires lifelong care to prevent or delay progression, with close collaboration between generalists and specialists. An improved understanding of the complex pathogenesis of Crohn’s disease and ulcerative colitis4 has led to a therapeutic strategy (Fig. 1) focused on hard end points (e.g., clinical and endoscopic remission)5 and precise molecular targeting of inflammatory cascades. Since the 1997 report on the use of infliximab6 (a monoclonal antibody against tumor necrosis factor α [TNF-α]) in patients with Crohn’s disease, three additional anti–TNF-α antibodies, two anti-integrin antibodies, a biologic agent against the p40 subunit of interleukin-12/23, a Janus kinase (JAK) inhibitor, and a sphingosine-1-phosphate (S1P)–receptor modulator have been approved for the treatment of IBD, expanding therapeutic options but complicating initial choices and subsequent treatment. In this review, we discuss how to initiate, switch, combine, and terminate such therapies.