The advent of biologic therapy has greatly accelerated the understanding and therapy of inflammatory bowel disease (IBD) and other diseases. The first biologic agent approved by the U.S. Food and Drug Administration (FDA) for use in IBD was infliximab in 1998. Since that time there has been substantial advancement in biologic therapies for the management of IBD, and numerous biologic agents are currently in trials.

Biologic therapies for IBD target specific pathways involved in the immune response and down regulate or prevent T-cell activation, induce T-cell apoptosis, interfere with leukocyte trafficking, and have other effects on the immune system that are still being unraveled. This chapter reviews current available biologic agents and those in advanced stages of clinical evaluation. As biologic agents become available and new data are obtained, the “when and how” to use biologic therapy has to be continuously re-evaluated and requires conscientious consideration of effectiveness, safety and cost, as well as the implications for future treatment options, bearing in mind that Crohn’s disease (CD) and ulcerative colitis (UC) are lifelong diseases. Current recommendations are to avoid use of combined therapy with two biologics. More controversial is the need, or lack thereof, for combined immunomodulator therapy along with a biologic agent. Data to help guide therapy on this issue will be forthcoming and will require careful appraisal.

Biologic therapies are divided into five classes: (i) natural or modified preparations of biologic origin such as blood products and vaccines consisting of live, attenuated, or dead organisms; (ii) recombinant peptides or proteins, such as erythropoietin, growth hormone, or cytokines; (iii) antibody-based therapies; (iv) nucleic acid-based therapies; and (v) cellular and gene therapies (1). A complete nomenclature has been established for monoclonal antibodies that end in the suffix “mab,” which gives some indication as to the origin and proposed mechanisms of the antibodies as well as other traits (2). Briefly, generic names containing the prefix “xi” in front of “mab,” such as infliximab or rituximab, denote chimeric products, whereas those containing “zu,” such as natalizumab, denote humanized products, and those without a “z” but still containing the “u,” such as adalimumab, are fully human.

Tumor necrosis factor-alpha (TNF-α) is a 51-kd trimeric cytokine consisting of three 17-kd inactive monomers (3). It exerts its proinflammatory property via a series of intracellular events that ultimately activate two major transcription factors, nuclear factor-κB and c-Jun. These activated transcription factors, in turn, trigger genes responsible for the components of the inflammatory response (4). The importance of TNF-α in the pathogenesis of IBD was not appreciated until dramatic responses were observed in CD patients treated with infliximab. We will discuss
three TNF-α antagonists (infliximab, adalimumab, and certolizumab pegol) and review their safety profile. The current data suggest that there is little difference in the efficacy (remission or response) between these anti-TNF agents in CD. The response and remission rates for infliximab in ACCENT I, adalimumab in CHARM, and certolizumab pegol in PRECiSE 2 trials are shown in Figure 8.1.