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P441. Influence of combination therapy with immune modulators on anti-TNF trough levels and antibodies in IBD patients

T. van Schaik, R.K. Roopram, P.W. Maljaars, M.H. Verwey, N. Ipenburg, J.C. Hardwick, R.A. Veenendaal, A.E. van der Meulen-de Jong, Leiden University Medical Center, Gastroenterology and Hepatology, Leiden, Netherlands


Patients with inflammatory bowel disease (IBD) are often treated with anti-TNF [infliximab (IFX) or adalimumab (ADA)]. It is important to identify factors that can reduce the incidence of immunogenicity against this medication. The objective of our study was to evaluate the influence of co-treatment with immune modulators on anti-TNF trough levels (TL) and antibodies against anti-TNF.


The records of all IBD patients at the Leiden university medical center who received either ADA or IFX in the year 2011 and/or 2012 (n = 352) were retrospectively evaluated with respect to assessment of TL and antibodies. A normal TL was defined as 3–7 µg/mL, a low TL as <3 µg/mL and a high TL as >7 µg/mL. Antibodies were positive if >12 AE/mL. Optimal dose of immunomodulator was defined as a normal TGN level (460–900 pmol/8x108 RBC) or daily doses of 2–2.5 mg/kg for azathioprine, 1–1.5 mg/kg for mercaptopurine or weekly >15 mg MTX. Combination therapy with immune modulators was defined as patients treated for a period of at least 10 weeks before assessment of TL and antibodies.


A total of 217 patients were included (108 patients IFX; 109 patients ADA). TL was known in 211 patients and antibodies in 203 patients (in 197 patients both TL and antibodies were assessed). The TL of ifx was low in 43 patients (42.6%), normal in 25 patients (24.8%) and high in 33 patients (32.7%). For ada the numbers were 10 (9.2%), 26 (23.9%) and 73 (67.0%) respectively. In 17 patients (15.7%) with IFX the antibodies were positive and in the ada group 21 patients (19.3%).

Mean TL in the infliximab group was higher in the combination therapy group (n = 56) compared to the monotherapy group (n = 46); 4.6 vs. 7.5 µg/mL; P = 0.04. In the ada group the difference was not significant (11.5 vs. 13.1 µg/mL). In patients with ifx monotherapy (n = 53), incidence of antibody formation was higher compared to patients with combination therapy (n = 47) (29.8% vs. 5.7%, P = 0.001). IFX patients with a subclinical dose immune modulator (n = 27) had a higher TL compared to patients who were optimally dosed (n = 29); P = 0.02. No differences in TL were observed for patients who immediately started with an immune modulator with those who did not. The incidence of antibody formation was lower in ifx patients who immediately started with immune modulators compared to patients who did not so (33.3% vs. 66.7%, P = 0.04).


Patients with IBD who were treated with ifx combination therapy were more likely to have higher trough levels and a lower incidence of antibodies. The dose of immune modulator was not of influence on the TL or presence of antibodies. For ada we did not see any difference.