Serum Ustekinumab Concentrations Are Associated With Remission in Crohn's Disease Defined by a Serum-Based Endoscopic Healing Index

Margaret Walshe; Krzysztof Borowski; Robert Battat; David Hudesman; Douglas C Wolf; Lauren Okada; Anjali Jain; Mark S Silverberg

doi:10.1093/crocol/otab032

Serum Ustekinumab Concentrations Are Associated With Remission in Crohn's Disease Defined by a Serum-Based Endoscopic Healing Index

Crohns Colitis 360. 2021 Jun 9;3(3):otab032. doi: 10.1093/crocol/otab032. eCollection 2021 Jul.

Authors

Margaret Walshe^{1

2}, Krzysztof Borowski^{1

2}, Robert Battat³, David Hudesman⁴, Douglas C Wolf⁵, Lauren Okada⁶, Anjali Jain⁶, Mark S Silverberg^{1

2}

Affiliations

¹ Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
² Division of Gastroenterology, Mount Sinai Hospital, Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
³ Jill Roberts Center for IBD, Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, New York, USA.
⁴ Inflammatory Bowel Disease Center, NYU Langone Health, New York, New York, USA.
⁵ Atlanta Gastroenterology Associates, Atlanta, Georgia, USA.
⁶ Prometheus Biosciences, San Diego, California, USA.

Abstract

Background: Optimal ustekinumab levels (UST) in Crohn disease (CD) treatment have not been defined. We set out to define the optimal UST to differentiate between remission and active CD, as defined using the serum-based endoscopic healing index (EHI).

Methods: Paired serum UST and EHI tests were analyzed. Remission was defined as EHI <20. Active disease was defined as EHI ≥50. The proportion of patients in remission was compared across UST quartiles. UST in subjects with EHI <20 and EHI ≥50 were compared. An area under receiver operating characteristic curve was generated to identify an optimal UST to differentiate between active disease and remission.

Results: A total of 337 unique patients were identified; median UST and EHI were 5.0 µg/mL [interquartile range (IQR) 2.7-9.1] and 37 (IQR 26-53), respectively. EHI <20 (remission) was found in 57 (16.9%) patients. EHI ≥50 (active disease) was found in 97 (28.8%) patients. Higher proportions of subjects were in remission for increasing UST quartiles, P = 0.01. Median UST in patients with EHI <20 and EHI ≥50 were 7.5 µg/mL (IQR 4.6-10.9) and 3.1 µg/mL (IQR 1.8-6.6), respectively, P < 0.001. An UST threshold of 3.75 µg/mL optimally differentiated between active disease and remission (area under the curve 0.725). UST levels >3.75 µg/mL were associated with a lower proportion of subjects with active disease (EHI ≥50; 18.9%) compared with UST levels ≤3.75 µg/mL (45.6%, P < 0.001).

Conclusions: Using the EHI, we identified a threshold UST level of 3.75 µg/mL to optimally differentiate between active and quiescent CD. These data suggest that UST serum concentrations of >3.75 µg/mL are optimally associated with endoscopic remission in CD.

Keywords: Crohn disease; endoscopic healing index; therapeutic drug monitoring; ustekinumab.