Analysis of possible drug interactions with mirikizumab

From a pharmacological perspective, as a therapeutic monoclonal antibody, Mirikizumab's potential drug interaction mechanism is significantly different from traditional small molecule drugs. It is not cleared directly by the hepatic metabolic enzyme system and is therefore unlikely to produce the classic metabolic interactions seen with oral small molecule drugs.

However, in chronic inflammatory diseases such as ulcerative colitis (UC) and Crohn's disease (CD), the long-standing inflammatory state itself may have indirect effects on drug metabolism. Research shows that in a chronic inflammatory environment, the levels of a variety of pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α, and interferon) increase, which may inhibit the expression and activity of cytochrome P450 (CYP450) enzymes in the liver, thereby affecting the metabolism rate of certain drugs.

When biologics such as militizumab are used that target the IL-23 pathway, as the inflammatory response is controlled and the levels of pro-inflammatory cytokines in the body decrease, the originally inhibited CYP450 enzyme activity may gradually recover. This change may lead to a decrease in the exposure level of CYP450-related substrate drugs in the body, thereby affecting their therapeutic effect. For patients who are taking concomitant CYP450 substrate drugs, there is a theoretical need to pay attention to changes in the efficacy of these drugs when initiating or discontinuing militizumab treatment.

Therefore, in the case of combined medication, it is usually clinically recommended to observe the efficacy or blood concentration of the relevant drugs and adjust the dosage if necessary. This interaction is not a direct drug antagonism, but more of an indirect metabolic effect caused by changes in inflammatory status, reflecting the systemic role of biological agents in overall immune regulation.

Reference: https://www.ema.europa.eu/en/documents/product-information/omvoh-epar-product-information_en.pdf