Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease.

Abstract

BACKGROUND AND AIMS:

Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease.

METHODS:

Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay.

RESULTS:

Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment.

CONCLUSIONS:

Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.

• Authors: Hiroaki Okuda, Shuhei Hosomi, Shigehiro Itani, Noriyuki Kurimoto, Yumie Kobayashi, Rieko Nakata, Yu Nishida, Masaki Ominami, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Noriko Kamata, Fumio Tanaka, Yasuaki Nagami, Koichi Taira, Satoko Ohfuji, Yasuhiro Fujiwara
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 38 Issue 6 Pg. 910-920 (Jun 2023) ISSN: 1440-1746 [Electronic] Australia
• PMID: 36807301 (Publication Type: Journal Article)
• Copyright: © 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Chemical References

• Ustekinumab
• Chemokine CCL2
• Biological Products

Topics

• Humans
• Ustekinumab (therapeutic use)
• Crohn Disease (drug therapy)
• Chemokine CCL2
• Remission Induction
• Biological Products (therapeutic use)
• Treatment Outcome