Background: Biosimilar infliximab CT-P13 received EMA approval in June 2013 for all indications of the originator product and its use is mandatory in all anti-TNF naïve IBD patients in Hungary since May 2014. In the present study we aimed to prospectively evaluate the immunogenicity profile of the biosimilar infliximab and predictors of TDM in IBD during the first year of therapy in a nationwide, multicentre cohort.
Methods: Demographic data were collected and a harmonized monitoring strategy was applied. Clinical and biochemical activity were evaluated at weeks 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 during the induction treatment.
Results: 353 consecutive IBD patients (209 CD patients and 144 UC patients) were included in the present cohort. 23.4% of CD patients and 19.4% of UC patients had received previous anti-TNF therapy. None of the patients had received infliximab within 12 months prior to initiation of the biosimilar infliximab. 60/51% of CD/UC patients received concomitant immunosuppressives at baseline.
Mean TLs were 18.9, 17.3, 7.4, 4.3 and 5.3 μg/ml at weeks 2, 6, 14, 30 and 54 in CD and 19.1, 11.8, 5.0, 3.9 and 4.5 μg/ml UC. Previous anti-TNF therapy was associated with lower early TL-s in both CD (week 2, 14, and 30, p<0.05) and UC (week 2 and 6, p=0.03).
ADA positivity rates were 4.3%, 12.0%, 20.9% and 28.6% in naïve patients at weeks 0, 14, 30 and 54 (ntotal=266, 312, 290 and 210). ADA positivity at week 14 was associated with lower TLs in all CD (week 2, 14 and 30, p<0.007 for all) and UC (week 6, 14 and 30, p<0.001 for all) patients.
Concomitant IS use prevented ADA formation in anti-TNF naïve patients (week 14, 30 and 54, p=0.01, 0.02 and 0.004) in CD but not in UC and did not affect clinical remission or response rates.
32 (8.9%) patients had infusion reactions during induction or maintenance treatment, of which 16 patients had received previous infliximab treatment.
Conclusions: Drug TLs and ADAs in IBD patients until week 54 were in line with results reported for the originator in previous studies. Patients with previous exposure to anti-TNFs had lower early TL coupled with ADA positivity and were more likely to develop infusion reactions. Concomitant IS use prevented ADA development in anti-TNF naïve patients.