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DOP062. Predictors of formation of antibodies to infliximab (ATI) and secondary loss of response in IBD patients treated with infliximab

B. Ungar1, U. Kopylov1, M. Yavzori1, E. Fudim1, O. Picard1, A. Lahat1, B. Avidan1, A. Lang1, B. Weiss2, Y. Chowers3, R. Eliakim1, S. Ben-Horin1, 1Chaim Sheba Medical Center, Gastroenterology, Ramat Gan, Israel, 2Chaim Sheba Medical Center Tel-Hashomer, Edmond & Lily Safra Children's Hospita, Ramat Gan, Israel, 3Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Gastroenterology department, Haifa, Israel

Background

Recent data suggest that antibodies to infliximab (ATI) develop in approximately 45% of IBD patients even when receiving scheduled infliximab therapy. The formation of ATI is associated with lower serum infliximab levels, infusion reactions and loss of clinical response (LOR). Pre-infusion steroids and concomitant immunomodulator therapy are known to decrease the risk of immunogenicity, whereas episodic therapy has the opposite effect. However, while various clinical and demographic factors have been linked with infliximab serum levels and clinical response, none have been systematically mapped out for ATI formation.

Objective: To investigate which clinical and demographic factors predict ATI formation (primary outcome) and secondary LOR (secondary outcome).

Methods

155 infliximab-treated IBD patients were followed prospectively between 2009 and 2013. Trough levels of infliximab and ATI were measured before each infusion by anti-lambda ELISA. Patients were monitored for disease activity by clinical activity indexes and for dose-intensification or infliximab cessation. Patients were stratified according to ATI formation and clinical response. The clinical and demographic parameters were analyzed for their association with the designated outcomes.

Results

1490 sera were tested during the course of treatment of these 155 patients. On multivariate analysis, episodic therapy was positively associated with developing ATI (OR 3.07, 95% CI 1.1–8.65, p = 0.034), whereas concomitant immunomodulator therapy was negatively associated with ATI formation (OR 0.38 95% CI 0.17–0.85, p = 0.017). All other variables including weight, smoking status, gender, type of IBD (CD vs. UC) or disease duration did not differ between patients who developed ATI and those who did not. With respect to secondary LOR, smoking at induction was predictive of LOR to infliximab (OR 7.9, 95% CI 1.77–35.3, p = 0.007). In addition, patients who did not develop LOR were younger than those who did (29.8±13.5 vs. 36.2±14, p = 0.008).

Conclusion

Formation of ATI is not associated with any individual patient characteristics, except for episodic therapy and concomitant immunomodulator therapy. Smoking is an independent risk factor for clinical LOR, while young age is a protective one. Since both were not associated with ATI formation, their effect on clinical response is probably not immunologically mediated.