tofacitinib and Demyelinating-Diseases

With a rapidly evolving complement of advanced targeted therapies in inflammatory bowel disease, additional safety and side effect concerns emerge. It is the purpose of this review to consider various risks with biologic therapies in inflammatory bowel disease and discuss mitigating strategies.. Two recently approved monoclonal antibodies (vedolizumab and ustekinumab) and a Janus kinase inhibitor small molecule (tofacitnib) have introduced a number of novel safety and risk considerations. We review the clinical trial and real-world safety data to date on these agents as well as review new data and considerations with anti-tumor necrosis factor agents. New vaccines for varicella zoster virus, hepatitis B virus, and high-dose influenza have been studied, and we discuss the clinical importance of these findings. Lastly, we make management recommendations in the event of particular side effects or complications. Understanding the risks of new agents in inflammatory bowel disease, potential mitigating strategies, and management considerations is important to achieving and maintaining clinical outcomes in IBD patients.

Topics: Antibodies, Monoclonal, Humanized; Biological Products; Demyelinating Diseases; Deprescriptions; Drug Substitution; Gastrointestinal Agents; Humans; Infections; Inflammatory Bowel Diseases; Lymphoma; Melanoma; Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Risk; Risk Assessment; Skin Neoplasms; Tumor Necrosis Factor-alpha; Ustekinumab

Iatrogenic demyelination is a distinct clinical subtype of central nervous system inflammatory disorders. The Janus kinase inhibitor, tofacitinib, is an oral disease-modifying antirheumatic drug that has shown contradictory effects on multiple sclerosis in animal models. In this report, we describe a novel case of reversible multifocal CNS demyelination in a patient with seropositive rheumatoid arthritis on tofacitinib. Although the mechanism is not completely understood, activation of T17 cells by tofacitinib and the subsequent increased production of interleukin-17 could be the cause. Moreover, a link between TNF-α and JAK/STAT pathways has been suggested, which may further explain the occurrence of iatrogenic demyelination in this case.

Topics: Animals; Demyelinating Diseases; Humans; Piperidines; Pyrimidines; Pyrroles