P308 Predictors of loss of response to adalimumab therapy: the importance of therapeutic drug monitoring in inflammatory bowel diseases
Z. Kurti*1, Z. Vegh1, M. Rutka2, L. Gonczi1, K. Farkas2, K. Gecse1, P. A. Golovics1, B. Szalay3, T. Molnar2, P. Lakatos1
1Semmelweis University, First Department of Medicine, Budapest, Hungary, 2University of Szeged, First Department of Medicine, Szeged, Hungary, 3Semmelweis University, Department of Laboratory Medicine, Budapest, Hungary
Therapeutic drug monitoring (TDM) may aid the therapeutic decision in patients with inflammatory bowel disease (IBD) who loose response to anti-tumour necrosis factor (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.
In total, 74 IBD patients (94 TDM measurements, Crohn’s disease [CD]/ulcerative colitis [UC] 59/15; male/female, 32/42 age; CD/UC, 38/31years; mean duration of adalimumab therapy CD/UC, 147.6/43.7 weeks) were enrolled in this consecutive cohort from 2 referral IBD centres in Hungary. Demographic data were comprehensively collected and a harmonised monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity at the time of trough level (TL) and antidrug antibody (ADA) measurement were recorded. Patients were evaluated either at the time of suspected loss of response (LOR) or during follow-up. TDM measurements were done by commercial ELISA (LISA TRACKER, Theradiag, France).
Amongst 74 IBD patients, the probability of ADA positivity and low TL (< 4.5 μg/mL) was 8.1% and 13.8% in the first year and 11.4% and 28.8% in the second year after start of adalimumab therapy in Kaplan–Meier analysis. The frequency of previous and current steroid and azathioprine exposure were 95.9%/29.7% and 73.3%/53.3%, and previous anti-TNF therapy was present in 74% (in CD 69% and in UC 93.3%) in the IBD cohort. Dose intensification was needed in 38.7% during the study period. The combination of normal TL and no ADA, normal TL and high ADA, low TL and no ADA, and low TL and high ADA were observed in 63.5%, 6.8%, 23% and 6.8% at TDM measurement. Predictors of the dose intensification were female gender (p = 0.06, HR 2.1), concomitant steroid therapy (p = 0.01, HR 2.57), and ADA positivity (p = 0.005, HR 3.26) with Cox regression model (p < 0.05). Predictors of loss of response were female gender (p = 0.004, HR 4.9), dose intensification (p = 0.009, HR 3.75), and there was a positive trend for concomitant steroid therapy (p = 0.06, HR 2.71) and previous anti-TNF therapy (p = 0.15, HR: 2.39). Predictors remained unchanged if the 94 TDM episodes were analysed separately.
Our results suggest that ADA development, low TL, and need for dose intensification are frequent during adalimumab therapy, and they support the use of routine TDM assessment in IBD patients. Female gender, concomitant steroid therapy, and ADA positivity were predictors of dose intensification, and female gender and dose intensification predicted loss of response.
Figure 1. Probability of ADA positivity during adalimumab therapy.