P517 Ustekinumab monitoring levels predict the need for intensification in patients with inflammatory bowel disease.
Ramos Lopez, L.(1);Ramos-Díaz, R.(2);Alonso-Abreu, I.(1);Mourani-Padron, I.(2);Carrillo-Palau, M.(1);Reygosa, M.C.(1)*;Medina-Chico, S.(1);Gutierrez-Nicolas, F.(3);Nazco-Casariego, G.J.(3);Hernandez-Guerra, M.(4);
(1)Hospital Universitario De Canarias, IBD Unit. Gastroenterology Department, La Laguna, Spain;(2)Hospital Universitario de Canarias, Fundación Canaria Instituto de Investigación Sanitaria de Canarias FIISC, La Laguna, Spain;(3)Hospital Universitario de Canarias, Hospital Pharmacy Department, La Laguna, Spain;(4)Hospital Universitario de Canarias, Gastroenterology Department, La Laguna, Spain;
Background
Therapeutic drug monitoring (TDM) is a valuable tool to optimize anti-TNF biologics in inflammatory bowel disease (IBD). However, for the non-anti-TNF agents (such as Ustekinumab-UST- an anti-IL12/23) TDM value and evidence in real-world IBD patients is scarce although emerging data suggest that higher drug concentration (>4.5 µg/ml) of these biologics agents predicts better clinical outcomes. We evaluated associations between UST levels and clinical outcomes in real-world IBD patients.
Methods
A cross-sectional study was performed in IBD patients who received maintenance therapy (≥16 weeks) with UST and followed in our IBD unit between June 2020 and May 2021. UST trough concentration was assessed at the time of inclusion and clinical outcome were reviewed by starting UST use (PRE), at the time of blood extraction (inclusion-EXT), and after 6 months of follow-up (POST). Clinical response was determined by Harvey-Bradshaw Index (HBI) (clinical remission; HBI≤4 points or pMayo ≤2 points) and biochemical response by fecal calprotectin (FC) (biochemical response CF>50 % reduction from basal value and biochemical remission CF <150 g/kg). The need for surgery, intensification, or change of treatment at the end of the follow-up was registered.
Results
A total of 62 patients (53.2% male; mean age 46 (41-50) years; Crohn’s disease n=57/ ulcerative colitis n=3/indeterminate colitis n=2) were included. The time from diagnosis to initiation of UST treatment was 149 (122-176) months. 35.5% of patients received co-treatment with immunosuppressors and 95,6% had received previous biologic agents (15,6% more than 2 previous biologics). The mean time of UST use was 13 (10-16) months. The mean UST level was established at 7.1 µg/ml (SD 4.3) with higher levels in intensified patients (UST every 4 weeks; n=17) at the time of extraction (9.4 µg/ml (4.3) vs. 6.2 µg/ml (4.0); p= 0.03). However, no differences were found in UST levels between patients achieving clinical remission (n=52,83.9%)) compared to non-responders (7.2 µg/ml (4.4) vs. 6.7 µg/ml (4.4), respectively; p=0. 71); nor in those achieving biological remission at 6 months (n= 31, 56.4%)) compared to non-responders ((7.0 µg/ml (4) vs 6.6 µg/ml (4.5), respectively; p= 0.7). Only 2 patients discontinued UST treatment and 7 patients needed to intensify treatment every 4 weeks during follow-up. In logistic regression analysis, the UST level lower than 4.5 µg/ml showed an independent predictive value for the need for UST intensification in the subsequent 6 months (OR 5.7, 95% CI 1.01-32.9).
Conclusion
UST is an effective drug for achieving clinical and biological remission in patients with IBD. UST level (<4.5 µg/ml ) may guide the need for treatment intensification at 6 months.