Inflammatory bowel disease caused by anti-TNFα and anti-interleukin

Post by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Inflammatory bowel disease is a chronic disease of the gastrointestinal tract. It is generally believed that inflammatory bowel disease is the result of an abnormal immune response to a dysbiosis of the gut microbiota in a genetically susceptible individual. Inflammatory bowel disease caused by anti-TNFα and anti-interleukins is called secondary enteritis.

Anti-TNFα inhibitors are molecules that counteract the proinflammatory TNFα and they alter TNFα-mediated immune signaling in inflammatory pathways. Some examples of these agents are infliximab, adalimumab, and etanercept. They have been used to treat various immune-mediated rheumatic disorders, inflammatory bowel disease or extraintestinal manifestations associated with inflammatory bowel disease, such as ankylosing spondylitis, uveitis , erythema nodosum and pyoderma. Treatment of one autoimmune condition can sometimes lead to another due to altered immune homeostasis. Interestingly, people exposed to an anti-TNF agent can develop new-onset inflammatory bowel disease or a drug-induced form of inflammatory bowel disease. Similarly, new-onset psoriasis or eczema has been reported following exposure to anti-TNF agents. For example, the use of infliximab for the treatment of inflammatory joint diseases associated with inflammatory bowel disease and not related to inflammatory bowel disease has been shown to induce autoimmune conditions such as drug-induced lupus, autoimmune hepatitis, and autoimmune disease. multiple sclerosis. In some cases, a paradoxical reaction was observed following administration of the drug, in which individuals without prior inflammatory bowel disease with inflammatory bowel disease developed joint disease associated with new-onset inflammatory bowel disease
Etanercept Etanercept , an anti-TNFα agent, has been widely used to treat rheumatoid arthritis, while ineffective in the treatment of inflammatory bowel disease. In fact, the use of this agent has been shown to be associated with the development of new-onset inflammatory bowel disease in many clinical observations. In a large case series of patients receiving etanercept for various rheumatic disorders, 49 developed new-onset inflammatory bowel disease. The median duration of treatment before the onset of symptoms was 3.58 months. Its use has also been associated with the precipitation of pre-existing ulcerative colitis.
In a French study, the mean frequency of etanercept-related new-onset inflammatory bowel disease was approximately 0.15%. In the same study, two patients treated with infliximab developed inflammatory bowel disease. In another large study of 17018 patients with auto-immune disorders, some were receiving etanercept, infliximab, or adalimumab. People on etanercept showed a significantly increased risk of developing new-onset ulcerative colitis or Crohn's disease, but did not see the same effect with infliximab or adalimumab. In one case report, a 56-year-old man with psoriasis treated with adalimumab developed new-onset ulcerative colitis. His ulcerative colitis reacted to the anti-IL-12/23 agent, ustekinumab.
Issues to be Explored The phenomenon of paradoxical responses to agents such as infliximab, adalimumab, or etanercept leading to the development of new-onset inflammatory bowel disease needs further exploration. The authors hope that ongoing research can identify individual disease genetic pathways for each patient, which will help select their appropriate therapeutic agent and pave the way for personalized medicine in the care of inflammatory bowel disease. Another emerging aspect of IBD therapy is the use of biosimilars, which need further investigation for their ability to induce new-onset inflammatory bowel disease leading to inflammatory bowel disease.

Anti-TNFα agents such as infliximab and adalimumab have become the preferred therapy for the treatment of inflammatory bowel disease. Recently, an anti-interleukin agent, ustekinumab (anti-IL-12/23) was approved for the treatment of Crohn's disease and ulcerative colitis. This agent has been successfully used to treat psoriasis and other rheumatic diseases over the past decade. Other anti-interleukins have been formulated to have anti-inflammatory effects; and they include, but are not limited to; secukinumab, an anti-IL-17A agent used to treat psoriasis, and tocilizumab, an anti-IL-6R inhibitor used to treat rheumatoid arthritis. In a separate study, both agents were found to be associated with exacerbation of pre-existing inflammatory bowel disease. These agents may even cause new-onset inflammatory bowel disease in at-risk individuals. The authors therefore recommend that novel agents, which may have potential for the treatment of immune-mediated disorders such as inflammatory bowel disease, should be thoroughly investigated for their immunogenicity and association. them with the development of new-onset inflammatory bowel disease.

Reference
Ray G. Inflammatory bowel disease in India - Past, present and future. World J Gastroenterol. 2016;22:8123-8136. [PubMed] [DOI] [Cited in This Article: 1] [Cited by in CrossRef: 23] Ghouri YA, Tahan V, Shen B. Secondary causes of inflammatory bowel diseases. World J Gastroenterol 2020; 26(28): 3998-4017 [PMID: 32821067 DOI: 10.3748/wjg.v26.i28.3998]