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* = Presenting author

DOP033 Immunogenicity profile and predictors of TLs and ADA development of biosimilar infliximab during the first 6 months of the therapy: results from a prospective nationwide cohort

B. Lovasz*1, Z. Kurti1, M. Rutka2, Z. Vegh1, K. Gecse1, K. Farkas2, J. Banai3, L. Bene4, B. Gasztonyi5, T. Kristof6, L. Lakatos7, P. Miheller8, K. Palatka9, A. Patai10, A. Salamon11, T. Szamosi3, Z. Szepes12, E. Biro13, G.T. Toth14, A. Vincze15, T. Molnar2, P. Lakatos1

1Semmelweis University, First Department of Medicine, Budapest, Hungary, 2University of Szeged, First Department of Medicine, Szeged, Hungary, 3Military Hospital, State Health Centre, Department of Gastroenterology, Budapest, Hungary, 4Peterfy Hospital, First Department of Medicine, Budapest, Hungary, 5Zala County Hospital, Second Department of Medicine, Zalaegerszeg, Hungary, 6B-A-Z County and University Teaching Hospital, Second Department of Medicine, Miskolc, Hungary, 7Csolnoky F. Province Hospital, Department of Medicine, Veszprem, Hungary, 8Semmelweis University, Second Department of Medicine, Budapest, Hungary, 9University of Debrecen, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary, 10Markusovszky Hospital, First Department of Medicine and Gastroenterology, Szombathely, Iceland, 11Tolna County Teaching Hospital, First Department of Gastroenterology, Szekszard, Hungary, 12University of Szeged, First Department of Internal Medicine, Szeged, Hungary, 13Semmelweis University, Department of Laboratory Medicine, Budapest, Hungary, 14Janos Hospital, Department of Gastroenterology, Budapest, Hungary, 15University of Pécs, First Department of Medicine, Pécs, Hungary

Background

Biosimilar infliximab CT-P13 received EMA approval in June 2013 for all indications of the originator product. Its use has been mandatory in all anti-TNF naïve IBD patients in Hungary since May 2014. In the present study, we aimed to evaluate prospectively the immunogenicity profile of the biosimilar infliximab and predictors of trough levels and anti-drug antibody development in IBD in a nationwide, multicentre cohort.

Methods

Demographic data were collected, and a harmonised monitoring strategy was applied. Clinical and biochemical activity were evaluated at week 14, 30, and 54. Routine therapeutic drug monitoring (TDM) was applied. Trough level (TL) and anti-drug antibody (ADA) concentration were measured by ELISA (LT-005, Theradiag, France) at baseline and at 2, 6, 14, 30, and 54 weeks, right before anti-TNF administration.

Results

In total, 291 consecutive IBD patients (184 CD patients and 107 UC patients) were included in the present cohort. 24.5% of CD patients and 14% of UC patients had received previous anti-TNF therapy. None of the patients had received infliximab within 12 months before initiation of the biosimilar infliximab. Further, 60%/52% of CD/UC patients received concomitant immunosuppressives at baseline. Mean TLs were 20.1, 14.7, 5.1, and 3.9 μg/ml at weeks 2, 6, 14, and 30, respectively. Early TLs were higher in CD compared with UC at weeks 2 (19.1 vs 15.1 μg/ml, p = 0.05) and 6 (16.7 vs 12.1 μg/ml, p = 0.046) with no significant differences in TLs thereafter at week 14 and 30. ADA positivity rates were 3.8%, 16.1%, and 24.1% in naïve patients at weeks 0, 14, and 30 (n total = 229, 192, and 143). TLs were lower at week 2 and 6 (p = 0.02 and p = 0.005) in patients with prior infliximab exposure, but not at week 14 or 30 in patients with previous anti-TNF exposure, as compared with naïve patients, which was coupled with higher ADA positivity. Concomitant IS use prevented early ADA formation in anti-TNF naïve patients (24.6% vs 11.2%, p = 0.03) by week 14, but this effect was lost by week 30 (29.8% and 21.2%, p = ns). 21 (7.2%) patients had infusion reactions during induction or maintenance treatment, of which 13 patients had received previous infliximab treatment.

Conclusion

Drug TLs and ADAs in IBD patients at weeks 0, 2, 14, and 30 were in line with results reported for the originator in previous studies. Early TLs were slightly lower in UC compared with CD. Patients with previous exposure to anti-TNFs had lower early TL coupled with ADA positivity and were more likely to develop infusion reactions. Concomitant immunosuppressives prevented early but not later ADA development.