Risks and benefits of combining immunosuppressives and biological agents in inflammatory bowel disease: is the synergy worth the risk?
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Hospital,Chicago, IllinoisUSA
- Correspondence to:
Stephen B Hanauer
MD, Professor of Medicine and Clinical Pharmacology, and Chief, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Hospital, 5841 S. Maryland Ave., MC 4076, Chicago, Il 60637, USA;
- Crohn’s disease
- biologic therapy
- anti-tumour necrosis factor
- immunosuppressive agents
Since the introduction of infliximab to treat Crohn’s disease, combination therapy with immunosuppressants has reduced immunogenicity, without impacting efficacy. The availability of novel anti-TNF agents and potential combined toxicities question the risk/benefit of combination therapies.
Vermeire and colleagues have furthered our understanding of the effectiveness of concomitant immunosuppressive therapy in suppressing formation of antibodies to infliximab in Crohn’s disease (see page 1226).1 The Leuven group has continued to demonstrate that immunosuppressive therapy reduces antibody formation to infliximab when the biological agent is administered on an episodic basis, and that antibody formation against infliximab correlates with lower infliximab blood levels and an increased risk of infusion reactions. In a year in which we can anticipate the introduction of two additional biological agents targeting tumour necrosis factor (TNF)α (adalimumab and certolizumab) and, possibly, a third monoclonal antibody targeting α4 integrins (natalizumab) for the treatment of Crohn’s disease in the USA and Europe, the benefits and risks of combination therapy have become a primary focus of both efficacy and toxicity studies.
Monoclonal antibodies targeting TNFα are highly effective therapies for the treatment of Crohn’s disease (and, as shown with infliximab, ulcerative colitis). The initial studies of these biological agents have been performed in patients who have active Crohn’s disease despite ongoing treatment with aminosalicylates, corticosteroids and immmunosuppressants.2–4 In these short-term trials, response to the induction dosing has been independent of the concomitant therapy. However, in this patient population (refractory disease despite ongoing therapy) short-term treatment without maintenance dosing of the biological therapy has not translated into long-term results without maintenance dosing.5–8 Furthermore, scheduled maintenance dosing of infliximab has been more effective than episodic therapy.9 Whether maintenance therapy with a biological versus an immunosuppressive will be necessary after induction therapy with a biological10 in different patient …