Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Apr 3;30(4):660-670.
doi: 10.1093/ibd/izad065.

Systematic Review and Meta-analysis: The Association Between Serum Ustekinumab Trough Concentrations and Treatment Response in Inflammatory Bowel Disease

Abhinav Vasudevan  1 , Vivek Tharayil  1 , Laura H Raffals  1 , David H Bruining  1 , Michelle Becker  2 , Mohammad Hassan Murad  3 , Edward V Loftus Jr  1
Affiliations
Meta-Analysis

Systematic Review and Meta-analysis: The Association Between Serum Ustekinumab Trough Concentrations and Treatment Response in Inflammatory Bowel Disease

Abhinav Vasudevan et al. Inflamm Bowel Dis. .

Abstract

Background: Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease.

Methods: A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission.

Results: We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn's disease) or endoscopic remission (290 patients, all with Crohn's disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations.

Conclusion: Based on the results of this meta-analysis primarily relating to patients with Crohn's disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.

Keywords: Crohn’s disease; biologics; monoclonal antibodies; therapeutic drug monitoring; ulcerative colitis.

Plain language summary

This meta-analysis of 14 observational studies found an association between better clinical outcomes and higher trough ustekinumab levels for maintenance treatment in inflammatory bowel disease.

PubMed Disclaimer

Conflict of interest statement

A.V., V.T., M.B., M.H.: none to declare

L.R.: Advisory boards: Janssens Pharmaceuticals, Fresenius Kabi

D.B.: Consulting: Janssens Pharmaceuticals

E.V.L.: Consulting for AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, CALIBR, Celgene, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Scopes, Janssen, Morphic, Ono Pharma, Pfizer, Protagonist, Sun Pharma, Surrozen, Sun Pharma, Takeda, UCB; research support from AbbVie, Bristol-Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, UCB.

Figures

Figure 1.
Figure 1.
Study selection process.
Figure 2.
Figure 2.
Meta-analysis of mean ustekinumab trough concentration for remission and nonremission.
Figure 3.
Figure 3.
Meta-analysis of clinical and endoscopic remission based on ustekinumab trough concentration quartiles in Crohn’s disease (CD) and ulcerative colitis (UC).
Figure 4.
Figure 4.
Meta-analysis of clinical remission rates based on ustekinumab trough concentration cutoff value in Crohn’s disease (CD) for (A) clinical remission and (B) endoscopic remission.
See this image and copyright information in PMC

References

    1. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-9.e3. - PubMed
    1. Cheifetz AS, Abreu MT, Afif W, et al. A comprehensive literature review and expert consensus statement on therapeutic drug monitoring of biologics in inflammatory bowel disease. Am J Gastroenterol. 2021;116(10):2014-2025. - PMC - PubMed
    1. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. - PMC - PubMed
    1. Feagan BG, Sandborn WJ, Gasink C, et al. ; UNITI–IM-UNITI Study Group. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946-1960. - PubMed
    1. Adedokun OJ, Xu Z, Gasink C, et al. Pharmacokinetics and exposure response relationships of ustekinumab in patients with Crohn’s disease. Gastroenterology. 2018;154(6):1660-1671. - PubMed