Category: Monday Poster Session

P1314 - Association of Ustekinumab Concentrations Using Anser® UST Mobility Shift Assay and Clinical Response in Crohn’s Disease

Monday, Oct 16
10:30 AM – 4:00 PM

Category: IBD       

Brigid S. Boland, MD1, Kelly Hester, PhD2, Jared Salbato, MS2, Kevin Chon, BS2, Raymond Christie, BS2, Elisabeth Evans, MSN, FNP3, Mark Renshaw, PhD2, Larry Mimms, PhD2, Anjali Jain, PhD2, William J. Sandborn, MD4
1University of California San Diego, La Jolla, CA; 2Prometheus Laboratories, Inc., San Diego, CA; 3UC San Diego Health Care System, La Jolla, CA; 4University of California, La Jolla, CA
Introduction: Ustekinumab (UST), a monoclonal antibody to the p40 subunit shared by interleukins-12 and -23, is approved for treatment of patients with Crohn’s disease (CD). Concentrations of other monoclonal antibodies to tumor necrosis factor alpha (TNFa) have been associated with clinical and endoscopic outcomes in CD. The aim of this study was to measure UST concentrations and antibodies to UST (ATU) in sera from patients with Crohn’s disease using a commercial grade, drug tolerant test ANSER®UST.

Methods: A homogenous mobility shift assay (HMSA) was developed and validated for measuring UST and ATU concentrations in human serum samples. Serum specimens (N=19) from anti-TNFα refractory CD patients receiving UST maintenance treatment were analyzed (Table 1). Clinical response was defined as >50% reduction in symptoms based on physician global assessment (scores of 0-3: ranging from 0 indicating a lack of response to 3 indicating complete response). Mucosal healing was defined as the absence of ulcers on endoscopy. Serum concentrations of CRP and TNFa were measured using electrochemiluminescent and immunoassays, respectively. Two-sample t-test and Fisher’s Exact test were used for the statistical analysis. P-value < 0.05 was considered significant.

Results: Dynamic range for the quantitation of ANSER®UST test was 1.56-25 µg/mL (UST) and 1.56-100 U/ml (ATU), inter- and intra-assay precision was < 10% CV and accuracy was within 20%. A wide range of serum UST concentrations were observed in the analyzed patient cohort (min: 0.78 µg/mL, max: 20.85 µg/mL), but ATU was not detected in any patient. The median drug concentrations for clinical responders were significantly higher than the non-responders (5.8 µg/mL vs 2.2 µg/mL, p=0.0025) while the median CRP concentrations were lower (2.8 µg/mL vs 10.2 µg/mL, p=0.03) (Figure 1). Patients with mucosal healing had numerically higher median UST concentrations (4.6 µg/mL vs 3.9 µg/mL, p=0.16); however, this was not statistically significant.

Discussion: Using a drug-tolerant ANSER®UST test, serum UST concentration was associated with clinical response in a real world biologic-experienced CD patient population. Though the number of patients was small, this study demonstrated the utility of serum UST monitoring. A larger cohort of patients will be needed to determine the optimal clinical cut-offs of serum UST that may predict UST responsiveness.

Supported by Industry Grant: Yes

Disclosures: Does Disclose

Brigid Boland: Abbvie – Consultant. Janssen – Grant/Research Support. Takeda – Grant/Research Support.
Kelly Hester: Prometheus Laboratories – Employee.
Jared Salbato: Prometheus Laboratories – Employee.
Kevin Chon: Prometheus Laboratories Inc. – Employee.
Raymond Christie: Prometheus – Employee.
Elisabeth Evans: Abbvie – Speaker's Bureau. Janssen – Speaker's Bureau. Takeda – Speaker's Bureau. UCB – Speaker's Bureau.
Mark Renshaw: Prometheus Laboratories – Employee.
Larry Mimms: Prometheus Laboratories – Employee.
Anjali Jain: Prometheus Laboratories Inc. – Employee.
William Sandborn: Janssen – Consultant. Prometheus Labs – Consultant.

Table 1. Patient Characteristics

Subjects (N) 19
Age (median in years [IQR]) 37.5 [21-60]
% Male 68%
% Concomitant immune modulator 84%
>/= 1 Prior surgery 63%
% Prior TNF antagonists 100%
% Prior integrin inhibitor 53%
Median UST treatment duration (months [IQR]) 8.7 [3-40]

Serum UST and CRP Concentrations in Clinical Responders and Non-Responders

Citation: . ASSOCIATION OF USTEKINUMAB CONCENTRATIONS USING ANSER® UST MOBILITY SHIFT ASSAY AND CLINICAL RESPONSE IN CROHN’S DISEASE. Program No. P1314. World Congress of Gastroenterology at ACG2017 Meeting Abstracts. Orlando, FL: American College of Gastroenterology.

Brigid S. Boland

Assistant professor
University of California San Diego
La Jolla, California