Abstract | BACKGROUND & AIMS: METHODS: We collected data from 2 phase 3 trials (1 induction and 1 maintenance), in which patients with moderate to severe ulcerative colitis received an intravenous induction dose of ustekinumab (130 mg, n = 320; or approximately 6 mg/kg, n = 322). Responders were assigned randomly to groups that received subcutaneous maintenance ustekinumab (90 mg) every 8 weeks (n = 176) or 12 weeks (n = 172), or placebo (n = 175). We evaluated the association between ustekinumab concentration and efficacy, serum based on clinical effects (Mayo score), histologic features, and inflammation (measurement of C-reactive protein, fecal calprotectin, and fecal lactoferrin), as well as safety ( infections, serious infections, and serious adverse events), during induction and maintenance therapy. Optimal serum concentrations of ustekinumab were identified using receiver operating characteristic curve analyses. RESULTS: In patients with ulcerative colitis, dose-proportional serum concentrations of ustekinumab, unaffected by prior biologic or concomitant immunomodulator therapy, reached steady state by the second maintenance dose; the median trough concentration for dosing every 8 weeks was approximately 3-fold that of dosing every 12 weeks. Serum concentrations were associated with clinical and histologic features of efficacy and normalization of inflammation markers. The week-8 concentration threshold for induction of response was 3.7 μg/mL. A steady-state trough serum concentration of 1.3 μg/mL or higher was associated with a higher rate of clinical remission compared with patients who had lower serum concentrations. Serum concentrations of ustekinumab were not associated with infections, serious infections, or serious adverse events. CONCLUSIONS:
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Authors | Omoniyi J Adedokun, Zhenhua Xu, Colleen Marano, Chris O'Brien, Philippe Szapary, Hongyan Zhang, Jewel Johanns, Rupert W Leong, Tadakazu Hisamatsu, Gert Van Assche, Silvio Danese, Maria T Abreu, Bruce E Sands, William J Sandborn |
Journal | Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
(Clin Gastroenterol Hepatol)
Vol. 18
Issue 10
Pg. 2244-2255.e9
(09 2020)
ISSN: 1542-7714 [Electronic] United States |
PMID | 31816446
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antibodies, Monoclonal
- Ustekinumab
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Topics |
- Antibodies, Monoclonal
- Colitis, Ulcerative
(drug therapy)
- Crohn Disease
(drug therapy)
- Humans
- Remission Induction
- Treatment Outcome
- Ustekinumab
(adverse effects)
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