Continuous Therapy With Certolizumab Pegol Maintains Remission of Patients With Crohn's Disease for up to 18 Months

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Background & AIMS

The safety and efficacy of maintenance therapy with the anti–tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease.

Methods

Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, prospective, open-label extension trial in which patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date, and were not offered the option to increase their dose. Disease activity was measured by the Harvey–Bradshaw Index.

Results

Harvey–Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 after the start of PRECiSE 2 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group.

Conclusions

Certolizumab pegol effectively maintains remission of Crohn's disease for up to 18 months. Continuous therapy is more effective than interrupted therapy.

Section snippets

Study Design

PRECiSE 3 (www.clinicaltrials.gov; NCT00160524) is an ongoing, open-label extension study that included patients who completed 26 weeks of therapy in the PRECiSE 2 trial. The methodology of PRECiSE 2 has been published previously.12, 13 All patients were aged 18 years and older with moderate-to-severe Crohn's disease (defined by a CDAI score between 220 and 450 points) affecting the terminal ileum, colon, or both the ileum and colon for at least 3 months' duration before screening. Diagnoses

Patients and Demographics

In the PRECiSE 2 study, 428 of 668 patients (64.1%) responded to certolizumab pegol induction therapy at week 6 (ie, CDAI decrease of ≥100 points from baseline) and were randomized to receive either certolizumab pegol or placebo maintenance treatment.13 Of the 428 patients, 215 and 210 patients were randomized and received certolizumab pegol or placebo, respectively (3 randomized patients were excluded because of possible unblinding), and 151 patients (69.9%) and 109 patients (51.4%),

Discussion

These results from the PRECiSE 3 trial represent safety and efficacy data from a clinical trial of patients with Crohn's disease receiving either continuous or interrupted anti–TNF-α therapy beyond 12 months without the option to increase the dose. In clinical practice, anti–TNF-α therapy might be stopped temporarily when there is a serious infection such as pneumonia. Therefore, clinical trial data on the potential implications of interrupted therapy provide directly relevant clinical

Acknowledgments

Medical writing assistance was provided by Lisa Thomas, PhD (PAREXEL, West Sussex, UK) and was funded by UCB, Brussels.

A committee of academic investigators and UCB scientists designed the study. The trial was registered with clinicaltrials.gov (NCT00160524). Data were collected by ICON Clinical Research, Hampshire, United Kingdom, and were analyzed by UCB. The academic authors vouch for the veracity and completeness of the data and data analyses.

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    Conflicts of interest The authors disclose the following: Gary R. Lichtenstein reports receiving consulting fees from Abbott Laboratories, Centocor, Ferring, Tanabe, Schering-Plough, Elan Pharmaceuticals, Genentech, Given Imaging, Millennium Pharmaceuticals, Proctor and Gamble, Prometheus, Salix, Shire, UCB Pharma, and Wyeth; receiving lecture fees from Abbott Laboratories, Centocor, Proctor and Gamble, Salix, and UCB Pharma; research with Abbott Laboratories, AstraZeneca, Bristol-Meyers Squibb, Proctor and Gamble, Salix, and Shire. Ole Ø. Thomsen reports receiving consulting fees from UCB and Zealand Pharma and receiving lecture fees from AstraZeneca, Dr Falk Pharma, Ferring, Otsuka Pharma, Pfizer, Schering-Plough, and UCB. Stefan Schreiber reports receiving consulting fees from Abbot Laboratories, Schering-Plough and its subsidiary Essex Pharma Solvay, and UCB; receiving lecture fees from Abbott Laboratories, Essex/Schering Plough, and UCB Pharma; and receiving grant support from Abbott and UCB Pharma. Ian C. Lawrance reports serving on the scientific advisory board and receiving consulting fees from Merck & Co, Abbott Laboratories, Pharmatel Fresenius Kabi, Janssen-Cilag Pharmaceuticals, Ferring Pharmaceuticals, and Schering-Plough; and receiving grant support from Abbott Laboratories and Orphan Australia. Stephen B. Hanauer reports serving as a consultant to and has been involved in clinical research with Abbot Laboratories, Bristol-Myers Squibb, Centocor, Elan Pharmaceuticals, Ferring Pharmaceuticals, Genentech, Proctor & Gamble, Prometheus, Salix, Shire, and UCB Pharma and serving as a consultant for AstraZeneca, GlaxoSmithKline, and Millennium Pharmaceuticals. Ralph Bloomfield is an employee of UCB. William J. Sandborn has received research support and served as a consultant for UCB Pharma, Centocor, and Abbott Laboratories.

    Funding This study was funded by UCB, Brussels, Belgium.

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