Michiel Voskuil

Course: MSc in Medicine, University of Groningen

Intern in: Departments of Genetics and Gastroenterology and Hepatology

Period: May - November 2015

Supervisors: Prof. R.K. Weersma, Dr. E.A.M. Festen and Drs. L.M. Spekhorst

Predicting response to anti-TNF therapy in Inflammatory Bowel Disease

Summary

Patients with severe inflammatory bowel disease (IBD) or disease refractory to immuno­modulation may require anti-TNFα therapy, which is the most effective medical therapy for IBD. However, in approximately 30% of patients there is no effect from induction therapy and longer term, sustained response rates are as low as 21-48%. Furthermore, the use of these agents is extremely expensive and they have a considerable risk of severe side effects. It would therefore be very useful to be able to identify those patients who are at risk of being a non-responder.

During my internship, I built a database consisting of all the IBD patients who have received anti-TNFα therapy in the University Medical Center Groningen. Outcome of therapy was determined according to clinical evaluation by the treating physician and by levels of inflammatory markers in blood and faeces. Patients with loss of response had significantly higher baseline CRP levels (p = 0.021). Crohn’s disease (p < 0.001, OR = 3.5) significantly predicted a maintained remission and patients in this group had significantly lower CRP (p = 0.028) and higher albumin (p = 0.014) levels after induction. Minor allele carriership of FAS, rs1800682 (p = 0.007, OR = 2.5) and FCGR2A, rs12142756 (p = 0.01, OR = 2.5) was significantly associated with a less favourable clinical response. Furthermore, carriers of the minor alleles of TNFRS1A, rs984337 (p = 0.016), FAS, rs7898005 (p = 0.04) and FASLG, rs10458360 (p = 0.009) were associated with a less favourable biochemical response (as measured by change in CRP).

Our promising associations with response to anti-TNFα therapy need tto be replicated in independent cohorts, but these findings could aid clinical decision-making regarding individualised treatment options for IBD patients in the future.

My experience

I did my mandatory research internship during the final year of my MSc course in Medicine. Since I’m very interested in gastroenterology, I approached Rinse Weersma to discuss the possibilities for a research internship. I knew his group focussed on IBD and genetics: IBD is one of the fields in gastroenterology I’m very interested in, but I had little experience with genetics.

However, I believe being detached to the genetics department worked out very well for me. Apart from their enormous expertise and willingness to help, I experienced a proper ‘research atmosphere’. This really encouraged me to work hard and it eventually led me to take up a PhD position, which will keep me in the genetics department for at least the next two years. I would highly recommend doing an internship in the Department of Genetics to anyone.