NOD2 and inflammatory bowel disease: Although the exact mechanism of IBD development in patients with AS who are on TNF inhibitors is unknown, it may involve a cytokine imbalance caused by these drugs. In genetically predisposed patients, such as those with NOD2/CARD15 gene mutations, TNF inhibition can activate autoreactive T cells, altering the inflammatory cytokine environment and leading to IBD. Additionally, since patients have a higher risk of IBD, paradoxical inflammatory conditions induced by TNF inhibition may unmask an underlying inflammatory disease [26-28].