Do Ustekinumab Trough and Antidrug Antibody Levels Post Induction Predict Treatment Failure?
McCrossan MA(1), O’Moráin N(1, 2), Kumar L(1, 2), Murphy B(2), Rowan C(1), Sheridan J(1), Cullen G(1, 2), Doherty G(1, 2).
1. Centre for Colorectal Disease, St. Vincent’s University Hospital, Elm Park, Dublin 4. 2. School of Medicine, University College Dublin, Dublin 4.
Ustekinumab (UST), a monoclonal antibody that blocks interleukins IL-12 and IL-23, is increasingly used in the treatment of Crohn’s disease and Ulcerative Colitis. While there is an established role for therapeutic drug monitoring [TDM] in other biologic agents, there is a paucity of data regarding the clinical utility of TDM for UST.
To determine whether loss of response (LOR) and treatment failure (TF) can be predicted by post UST-induction serum trough concentrations and antibody (ADA) levels.
A retrospective observational study of patients who received subcutaneous induction of UST, following LOR to anti-TNF, for treatment of Crohn’s disease in 2016 was performed. Drug trough levels had previously been measured post induction. Frozen serum samples used for this measurement were retrospectively tested for ADA levels using ELISA. Our IBD database and admissions data were analysed (2016-2022). Treatment failure was defined as switch to another biologic and/or surgery.
A total of 10 patients (female=1, mean age 38.5 y) had trough and ADA levels measured. During the 6 year follow-up period, 3 patients failed treatment (mean age 30 y) while 7 remained on UST (mean age 42 y). There was no difference in Crohn’s phenotype or smoking status between groups. Lower median trough (2.9mcg/ml vs 5.8mcg/ml, p=0.49) and higher median ADA levels (6.57 AU/ml vs 5.87 AU/ml, p=0.16) were noted in the TF group compared to those who continued on UST. All patients required dose escalation. All treatment failure patients were switched to alternative biologic agents, with 1 patient requiring surgery.
Ustekinumab trough and ADA levels may be useful in predicting LOR and TF. Further studies are required to determine whether this is clinically significant.