Original article
Alimentary tract
Association Between Plasma Concentrations of Certolizumab Pegol and Endoscopic Outcomes of Patients With Crohn's Disease

https://doi.org/10.1016/j.cgh.2013.10.025Get rights and content

Background & Aims

Monitoring plasma concentrations of anti–tumor necrosis factor agents could optimize treatment of patients with Crohn's Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD.

Methods

We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n = 80) and 54 (n = 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively.

Results

Higher concentrations of CZP at week 8 were associated with endoscopic response (P = .0016) and remission (P = .0302) at week 10 (n = 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P = .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P = .0014 and P = .0373, respectively).

Conclusions

Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti–tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.

Section snippets

Materials and Methods

The methods and results of the MUSIC trial (Clinicaltrials.gov identifier: NCT00297648) have been reported previously.9 MUSIC was a 54-week, multicenter, single-arm, open-label study assessing endoscopic improvement in patients with moderate to severe CD receiving CZP. Adult patients aged 18 years and older (N = 89) with active CD (CD Activity Index [CDAI] ≥220 and <450 scored during the 7 days before study drug initiation) for 3 or more months' duration were enrolled. Patients had to have at

Patient Disposition and Demographics

Demographics and baseline characteristics of the analysis set are listed in Table 1. A total of 80 patients had both baseline characteristic data and CZP plasma concentration determined at week 8. At week 10, a total of 45 patients who had an endoscopic measurement available also had a CZP trough measurement available at week 8; these patients had received a CZP 400-mg loading dose at weeks 0, 2, and 4. At week 54, after the maintenance dose of 400 mg CZP every 4 weeks, 18 patients had an

Discussion

This post hoc analysis of data from the MUSIC trial was designed specifically to evaluate the associations between CZP plasma concentrations and endoscopic and clinical outcomes, and to identify baseline factors associated with CZP plasma trough levels at week 8 after a loading dose and at 1 year (week 54) after maintenance therapy with CZP 400 mg every 4 weeks.

In this study, the geometric mean CZP plasma concentrations at week 8 (range, 11.1 ug/mL to 19.8 ug/mL) were generally lower than those

Conclusions

Endoscopic response and remission were associated with higher concentrations of CZP. The highest CZP plasma concentration quartiles were associated with higher rates of endoscopic response and remission at week 10. At week 54, the rates of endoscopic remission were correlated significantly with the CZP plasma concentration. Higher body weight and CRP concentrations were associated with lower CZP concentrations. The significant inverse relationship between CZP plasma concentration and baseline

Acknowledgments

Editorial assistance was provided by a contract medical writer (Ann P. Tighe, PhD, of PPSI [a PAREXEL company]), funded by UCB Pharma and by Matladi Ndlovu, PhD, of UCB Pharma.

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    Conflicts of interest These authors disclose the following: Jean-Frédéric Colombel has served as a consultant, advisory board member, or speaker for AbbVie, Amgen, Bristol Meyers Squibb, Celltrion, Ferring, Genentech, Giuliani SPA, Given Imaging, Merck & Co, Millenium Pharmaceuticals, Inc, Nutrition Science Partners, Ltd, Pfizer Inc, Prometheus Laboratories, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma, Vertex, and Dr. August Wolff GmbH & Co; William Sandborn has served as a consultant for Abbott Laboratories, AstraZeneca, LP, Centocor, Elan Pharmaceuticals, Inc, Ferring Pharmaceuticals A/S, Procter & Gamble, Prometheus Laboratories, Salix Pharmaceuticals, Inc, Schering-Plough Corporation, Shire Pharmaceuticals, Tillotts Pharma AG, and UCB Pharma; and has received financial research support from Abbott Laboratories, Astra Zeneca, LP, Centocor, Elan Pharmaceuticals, Procter & Gamble, Salix Pharmaceuticals, Schering-Plough Corporation, Shire Pharmaceuticals, Tillotts Pharma AG, and UCB Pharma; Matthieu Allez has served as a consultant for Abbott, UCB Pharma, Ferring, Merck Sharp and Dohme, Corp, TcLand, TxCell, Novo Nordisk, Pfizer, and GlaxoSmithKline; has received lecture fees from Merck Sharp and Dohme, Corp, Ferring, Neovacs, Janssen Cilag, and Abbott; and has received financial support for research from Novo Nordisk; Olivier Dewit has received fees from MSD, Abbott, and Ferring for speaking, and from MSD and Abbott for educational activities; Geert D'Haens has received consulting fees from UCB Pharma and has been paid to serve on speakers' bureau/advisory committees for UCB Pharma; Yoram Bouhnik has been reimbursed by Schering-Plough and Abbott for attending several conferences; and has been paid by Schering-Plough, Abbott, Ferring, Norgine, HAC Pharma, BMS, and Teva for running educational programs; Gerald Parker and Bosny Pierre-Louis are employees of UCB Pharma; and Xavier Hébuterne has received funding from UCB Pharma, AbbVie, Baxter, Fresenius Kabi, and Nestlé for advisory activities and as a member of an advisory board, and from AbbVie, Nestlé, Norgine, Nutricia, and MSD for educational activities. The remaining author discloses no conflicts.

    Funding The MUSIC study (NCT00297648) was funded by UCB Pharma.

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