TNF Inhibitors for IBD may Increase Risk of Immune-Mediated Inflammatory Diseases

Inflammatory bowel disease (IBD) patients treated with Tumor necrosis factor (TNF) inhibitors may face a surprising risk, according to a large national study. Researchers from Denmark and France analyzed data from over 100,000 individuals with IBD and found that TNF inhibitor use was associated with a 76% increase in the risk of developing other immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, psoriasis, and hidradenitis suppurativa.

The study, published in Clinical Gastroenterology and Hepatology, analyzed pooled data from the first 24 weeks of treatment, including cohorts from Denmark (HR 1.66) and France (HR 1.78), suggesting the findings were robust. The analyses were adjusted for various factors, including sex, IBD subtype and severity, IBD-related procedures, comorbidities, and medications.

Further comparisons between TNF inhibitors and another drug, azathioprine, showed that TNF inhibitors were associated with a significantly higher risk of IMIDs (HR 2.94). The study's lead author, Daniel Ward, PhD, from Aalborg University, and colleagues urged further research into the mechanisms causing this paradoxical effect of anti-TNF, which could have serious clinical implications.

While caution is advised in interpreting the results, as the study does not establish a causal relationship, the findings raise questions about the effects of TNF inhibitors on IMIDs. Joseph Feuerstein, MD, from Beth Israel Deaconess Medical Center, highlighted that patients should not discontinue their anti-TNF treatment based on this study. Additional research is needed to understand the implications of these findings on disease management.

"Our findings are unexpected and warrant further research into the mechanisms behind the paradoxical anti-TNF-caused occurrence of diseases that are normally indications for anti-TNF," Ward and colleagues wrote. "If correct, the paradoxical effect of anti-TNF could have serious clinical implications."

The researchers hypothesized that altering the immune system with TNF inhibitors might trigger the development of these IMIDs in susceptible individuals. They also noted that TNF inhibitors may dysregulate the immune system through altered paracrine signaling.

The study's limitations included a lack of information on smoking, an important risk factor for psoriasis in patients with IBD. Despite this, the findings suggest that TNF inhibitors could have an unexpected impact on the development of other inflammatory diseases. Further cohort studies involving patients with rheumatoid arthritis or psoriasis exposed to anti-TNF treatments are necessary to better understand this phenomenon.

Reference:

Clinical Gastroenterology and Hepatology Ward D, et al "Tumour necrosis factor inhibitors in inflammatory bowel disease and risk of immune mediated inflammatory diseases" Clin Gastroenterol Hepatol 2023; DOI: 10.1016/j.cgh.2023.06.025.