PMID- 36807301 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20230619 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 38 IP - 6 DP - 2023 Jun TI - Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease. PG - 910-920 LID - 10.1111/jgh.16151 [doi] AB - 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 naive 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. CI - (c) 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Okuda, Hiroaki AU - Okuda H AD - Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. FAU - Hosomi, Shuhei AU - Hosomi S AUID- ORCID: 0000-0002-8808-5672 AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Itani, Shigehiro AU - Itani S AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Kurimoto, Noriyuki AU - Kurimoto N AD - Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. FAU - Kobayashi, Yumie AU - Kobayashi Y AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Nakata, Rieko AU - Nakata R AUID- ORCID: 0000-0001-9977-7239 AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Nishida, Yu AU - Nishida Y AUID- ORCID: 0000-0003-3369-5059 AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Ominami, Masaki AU - Ominami M AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Nadatani, Yuji AU - Nadatani Y AUID- ORCID: 0000-0001-7081-8746 AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Fukunaga, Shusei AU - Fukunaga S AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Otani, Koji AU - Otani K AUID- ORCID: 0000-0001-9075-6415 AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Kamata, Noriko AU - Kamata N AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Tanaka, Fumio AU - Tanaka F AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Nagami, Yasuaki AU - Nagami Y AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Taira, Koichi AU - Taira K AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Ohfuji, Satoko AU - Ohfuji S AD - Department of Public Health, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Fujiwara, Yasuhiro AU - Fujiwara Y AD - Department of Gastroenterology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. LA - eng GR - 19K17472/KAKENHI/ PT - Journal Article DEP - 20230308 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - FU77B4U5Z0 (Ustekinumab) RN - 0 (Chemokine CCL2) RN - 0 (Biological Products) SB - IM MH - Humans MH - Ustekinumab/therapeutic use MH - *Crohn Disease/drug therapy MH - Chemokine CCL2 MH - Remission Induction MH - *Biological Products/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Crohn's disease OT - Monocyte chemoattractant protein-1 (MCP-1) OT - Predictor OT - Ustekinumab EDAT- 2023/02/23 06:00 MHDA- 2023/06/19 13:08 CRDT- 2023/02/22 11:31 PHST- 2022/12/21 00:00 [revised] PHST- 2022/09/04 00:00 [received] PHST- 2023/01/18 00:00 [accepted] PHST- 2023/06/19 13:08 [medline] PHST- 2023/02/23 06:00 [pubmed] PHST- 2023/02/22 11:31 [entrez] AID - 10.1111/jgh.16151 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2023 Jun;38(6):910-920. doi: 10.1111/jgh.16151. Epub 2023 Mar 8.