The introduction of anti-tumor necrosis factor-alpha agents has improved treatment options for patients with inflammatory bowel disease. However, these agents can also lead to increased vulnerability to infections, development of autoimmune diseases, malignancies, and decreased immunogenicity of vaccinations.
The introduction of anti-tumor necrosis factor-alpha (anti—TNF-α) agents has significantly improved treatment options for patients with inflammatory bowel disease (IBD), especially when their disease is refractory to or who cannot tolerate conventional therapies. The East Asian medical market currently offers 3 anti–TNF-α agents for the treatment of IBD: infliximab, adalimumab, and golimumab, which have been shown to be effective for inducing and maintaining long-term remission of IBD.
In addition, an infliximab biosimilar, CT-P13 (Inflectra, Remsima), which is approved in The Republic of Korea, the European Union, and the United States, has been shown in a Korean study to be well tolerated in IBD patients:
However, anti—TNF-α agents can also lead to increased vulnerability to infections, development of autoimmune diseases, malignancies, and decreased immunogenicity of vaccinations, notes Jae Hee Cheon, MD, PhD, in the July 2017 issue of the Journal of Gastroenterology and Hepatology. Cheon reviews anti—TNF-α treatments and their potential complications in East Asian patients, and urges clinicians to use customized treatment strategies to optimize therapy and minimize complications. He reminds clinicians that different genetic backgrounds and environmental exposures can result in discrepancies in therapeutic responses and occurrences of complications in IBD populations in Asian versus in Western countries.
Since TNF-α plays a crucial role in maintaining granulomas and immune responses against viral or intracellular bacterial pathogens, inhibition of this protein can lead to an increased risk of infection, such as reactivation of latent tuberculosis (TB), hepatitis B, and varicella zoster virus infection. Because infectious diseases such as TB, hepatitis, and influenza remain major health problems in East Asia, a more cautious use of biologics is needed, Cheon argues. Ideally, all IBD patients should receive vaccinations at the time of diagnosis to prevent a number of infectious diseases during immunosuppressive treatment. Some studies suggest that IBD patients are inadequately vaccinated, however, and there are concerns that anti—TNF-α agents may interfere with the immune response to vaccines. Thus, attention to proper and timely vaccinations for IBD patients is critical.
IBD itself involves risk factors for the development of intestinal malignancy, which is associated with the extent and duration of the disease, and age at diagnosis. Theoretically, the administration of anti—TNF-α agents also raises concerns for the development of malignancies, such as lymphoma, although TNF-α has been shown to limit the growth of tumors in some animal models. Treatment with biologics can also raise the risk of melanoma, Cheon points out, noting that although regular dermatological screening and protection against ultraviolet radiation are recommended in Caucasians, no such guideline exists for Asian patients with IBD. Guidelines for malignancy in Asian patients instead focus on the surveillance of colorectal cancer. “Guidelines for IBD patients must be established for other types of cancers that are prevalent in Asia, such as gastric cancer or thyroid cancer,” he says.
Other adverse events associated with anti—TNF-α treatment include hypersensitivity reactions, dermatological complications, arthralgia, cytopenia, congestive heart failure, demyelinating disease, a lupus-like syndrome, autoimmune liver injury, the induction of autoantibodies, and other systemic side effects.
In summary, while anti—TNF-α agents, including biosimilar CT-P13, have significantly improved clinical outcomes in many patients with IBD, the decision to use these agents should include a risk-benefit analysis of the drugs’ clinical efficacy and potential complications. Close monitoring and identification of individual risk factors for complications are important principles in biologic therapy, and tailoring treatment strategies to suit patients of specific ethnic groups is advised.