Scientific Exchange Tour NL -  Professor Shomron Ben-Horin – June 2018

Anti-TNF treatment optimization  

Prof. Ben-Horin is specialized in Crohn’s disease and ulcerative colitis and is the Director of the inflammatory bowel disease (IBD) service at the Gastroenterology Department of Sheba Medical Center, Israel and also heads the Gastro-Immunology Laboratory. He is a senior lecturer at the Sackler School of Medicine of the Tel-Aviv University and a member of the steering committee of the Israeli Gastro Association. His main research focus is drug mechanisms and response to biologic antibody drugs in IBD, as well as opportunistic infections in IBD.

Prof. Ben-Horin has been a distinguished invited speaker in many international medical conferences and has authored more than 110 medical articles and is an Associate Editor of the European Journal of Crohn’s & Colitis (JCC). In June 2018, prof. Ben-Horin will visit The Netherlands for the scientific exchange tour which aims to educate Dutch HCPs on anti-TNF treatment optimization.

During the past decades with the introduction of anti-TNF agents, the treatment of IBD has shifted from treating symptoms to  the prevention of functional intestinal damage and future disease complications2. The new treatment goal of IBD treatment is achieving (deep) clinical remission. To achieve this, optimization of therapy is essential, taking into account pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body does to the drug). A significant proportion of IBD patients lose response to their treatment while they initially responded to the treatment1. Literature studies found that loss of response (LOR) to anti-TNF agents after 12 months of therapy occurs in 23-46% of the patients when judged by dose intensification, or 5-13% when judged by drug discontinuation rates1. It is important to know the underlying mechanism for the LOR (disease characteristics, immunogenicity, treatment related factors).  Anti-TNF treatment optimization can regain response in patients with a primary non-response to anti-TNF, secondary non-response to anti TNF and patients who have previously failed on anti-TNF.

If the LOR is a result from the formation of anti-drug antibodies, concomitant use of an immunomodulator drug can help in regaining of clinical response and the elimination of the anti-drug antibodies. Retrospective studies have shown that combination therapy (anti-TNF with azathioprine) can prevent LOR and lower the risk of treatment cessation and surgeries.  Other studies have shown that switching patients with a LOR within anti-TNF class, 41-84% and 19-68% of the patients regained response on the short and long term respectively5,6. The same results were found for patients with LOR where dose escalation was applied.  

As with all drugs, it is assumed that anti-TNF agents need to be available in sufficient quantity in vivo to exert their effect. Studies have shown that low levels of anti-TNF are associated with loss of efficacy and worsened clinical outcome3 and higher anti-TNF concentrations at trough have been associated with improved outcomes in IBD (TAXIT trial). In addition, higher levels of anti-drug antibodies can be the reason for LOR.  Hence, in order to maintain remission in IBD patients, adequate serum levels are required and therapeutic drug monitoring (TDM), measurement of levels of drug and anti-drug antibodies, can be a valuable tool to gain insight around LOR. Depending on the measurements, various interventions can be undertaken in order to regain clinical response.

During the scientific exchange meetings with prof. Ben-Horin, expert in this field, it will be discussed how treatment optimization with anti-TNF agents in IBD treatment can be applied in order to improve treatment efficacy, prevent the formation of anti-drug antibodies, reduce side effects, discontinue unnecessary treatment and manage costs. Participants will be asked to bring their own cases and/or practical examples to the meeting to allow for proactive discussions.

Ben-Horin, S. & Chowers, Y. (2011). Review article: loss of response to anti-TNF treatments in Crohn’s disease. Alimentary Pharmacology and Therapeutics 33: 987-995.

Ben-Horin, S. (2015). Drug Level-based Anti-Tumor Necrosis Factor Therapy: Ready for Prime Time? Gastroenterology 148:1268-1281.

Ben-Horin, S. & Chowers, Y. (2014). Tailoring anti-TNF therapy in IBD: drug levels and disease activity. Nature reviews Gastroenterology & Hepatology 11, 243-255.

Strik, A.S., Bots, S.J., D’Haens, G. & Löwenberg, M. (2016). Optimization of anti-TNF therapy in patients with Inflammatory Bowel Disease. Expert Review of Clinical Pharmacology 9: 429-439.

Sandborn, W. J. et al. Ann. Intern. Med. 146, 829–838 (2007).

Ma, C. et al. Aliment. Pharmacol. Ther. 30, 977–986 (2009).

Dignass, A., Van Assche, G., Lindsay, J.O., Lémann, M., Soderholm, J., Colombel, J.F., Danese, S., D’Hoore, A., Gassull, M., Gomollón, F., Hommes, D.W., Michetti, P., O’Morain, O., Oresland, T., Windsor, A., Stange, E.F. & Travis, S.P.L. for the European Crohn’s and Colitis Organisation (ECCO). (2010) The second European evidence-based Consensus on the Diagnosis and management of Crohn’s disease: Current management. Journal of Crohn’s and Colitis (4): 28-62.