Conventional treatment in inflammatory bowel disease--recent trends. Immunosuppressants and biologic agents: should they or need they be used together? How to use immunosuppressive therapy better (and safer) tomorrow?

Abstract

Although the use of concomitant immunosuppressants (IS) with biologics has been demonstrated to reduce the immunogenicity of chimeric (infliximab), humanized (natalizumab), human (adalimumab) antibodies and antibody fragments (certolizumab pegol), to date concomitant IS with biologics has not impacted on the short or intermediate responses in the treatment of Crohn's disease in most induction and maintenance trials. The optimal strategy to reduce antibodies to infliximab is to use an induction and maintenance strategy rather than episodic therapy. Any potential benefit of concomitant IS use with biologic agents needs to be balanced against the risk of combination therapy including serious infections and the risk of neoplasia. The discovery of genetic polymorphism for production of thiopurine methyltransferase (TPMT), a key enzyme in the metabolism of thiopurine antimetabolites, has made it possible to rationalize therapy in terms of patient and dosage selection. TPMT screening prior to initiation of thiopurine antimetabolites is currently recommended to avoid treating patients with low or absent TPMT activity with potentially toxic doses of thiopurines. Routine monitoring of blood counts and liver enzymes is recommended even in individuals with normal TPMT activity. The ability to monitor thiopurine metabolites may make it possible to optimize therapeutic response by guiding clinicians on dose escalation.