Biologics Targeting in the Treatment of Inflammatory Bowel Disease: A Conundrum

Abstract

Inflammatory bowel disease is a chronic, gastrointestinal disorder which is classified into Crohns’ disease and ulcerative colitis. It has a strong effect on the quality of life and is characterized by chronic periods of exacerbation and remission. It has an unknown etiology but is driven due to excessive immune response in the gut wall. The triggered immune response causes overproduction of proinflammatory cytokines and adhesion molecules. Biological therapies are the monoclonal antibodies that are created in the laboratory to stop certain proteins in the body causing inflammation. These biologics have dramatically changed the therapeutic approach to inflammatory bowel disease. Biologics has three classes: anti-tumor necrosis factor (TNF), anti-integrins, and anti-interleukin (IL) 12/23. This article offers a critical evaluation of the efficacy and safety of biological agents in the management of inflammatory bowel disease. We compared different studies that were available in the PubMed database. All the biologics showed a better clinical response and mucosal healing than placebo. Infliximab has the highest efficacy, but it can make antibodies to infliximab that causes loss of response; then golimumab is effective in these patients. Certolizumab is more effective if it is used as a first-line drug. If corticosteroid and immunomodulator therapy has failed then vedolizumab is effective. As steroid therapy causes major adverse effects and involves the whole body, biological therapy should take over. Still, we need more studies to make biological therapy as a first option in the treatment of inflammatory bowel disease.

Biological Treatments in Inflammatory Bowel Disease: A Complex Mix of Mechanisms and Actions

“…It was later used also for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis. It binds both soluble and transmembrane forms of TNF-α and causes cell lysis of macrophages and T cells [51]. Infliximab induces and maintains clinical remission and mucosal healing in patients with IBD that are refractory or unresponsive to non-biologics treatment, and even works in the treatment of perianal fistulas [52,53].…”

“…It blocks the binding of TNF-α to its receptors in an identical manner to the natural human IgG1. This leads to the lysis of cells with transmembrane TNF-α [51]. With a longer half-life than infliximab, approximately 10-13 days, it requires less frequent administration, which is subcutaneous.…”

“…Results from some studies showed clinical benefits in patients refractory to other biological therapies [58]. Earlier studies showed more effectiveness when it is used as first-line agent [51].…”

“…The anti-integrin drug natalizumab is a recombinant humanized IgG4 that targets the α4 subunit of the integrins α4β1 and α4β7 on leukocytes. This drug stops the migration of inflammatory cells across the cell layers and needs to be administered for a long term to achieve positive results [51]. In the very beginning, this drug was approved by the FDA for multiple sclerosis treatment and later for CD, but it is only used in moderate to severe cases of CD due to its adverse effects [65], particularly progressive multifocal leukoencephalopathy (which is associated with the blockade of α4β1 integrin/VCAM-1 interactions by this drug in the central nervous system) [69,71].…”

“…However, its efficacy may be greater in IBD patients naïve to anti-TNF-α therapy [72,73]. It is very specific and could push IBD patients to remission [51]. This therapy seems to be more effective than anti-TNF-α therapy in the maintenance phase [74] but requires longer treatment times to exert its full effect [69].…”