Background: Therapeutic drug monitoring (TDM) measuring drug trough levels (TL) and antidrug antibodies (ADA) may aid the therapeutic decision in patients with inflammatory bowel disease (IBD) who loose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response to adalimumab therapy and the role of the therapeutic drug monitoring to predict the loss of response in adalimumab treated IBD patients.
Methods: 112 IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years, mean duration of adalimumab therapy CD/UC: 157.8/70.1 weeks) were enrolled in this consecutive cohort from two referral IBD centres in Hungary. Demographic data were comprehensively collected and a harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity at the time of the TL and ADA measurement were recorded. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were done by commercial ELISA (LISA TRACKER, Theradiag, France).
Results: Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%.The probability of ADA positivity and low TL (<4.0 μg/mL) was 12.1% and 17.8% in the first year and 17.3% and 29.5% and in the second year after start of adalimumab therapy in Kaplan-Meier analysis. Dose intensification was needed in 29.5% during the study period. There was an association between female gender, ADA positivity and LOR (female gender: p<0.001, OR: 7.770 CI95%: 2.483–24.315, ADA positivity: p=0.007 OR: 3.616 CI95%: 1.374–9.518)), while no other parameters, including TL was associated with LOR or dose intensification.
Conclusions: Our results suggest that ADA development, low TL and need for dose intensification are frequent during adalimumab therapy and support the use of routine TDM assessment in IBD patients. Female gender, and ADA positivity were predictors of loss of response.