Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-year results from the PRECiSE 3 study.

Abstract

BACKGROUND:

The efficacy and safety of certolizumab pegol (CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies (PRECiSE 1 & 2).

AIM:

To report the safety and efficacy outcomes of long-term, CZP therapy from PRECiSE 3, in which patients received treatment up to 7 years treatment.

METHODS:

Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400 mg, open-label, every 4 weeks (without additional induction therapy) for up to 7 years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation.

RESULTS:

A total of 595 patients entered the study; 117 (20%) completed 7 years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were ≥68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively.

CONCLUSION:

Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7 years. ClinicalTrials.gov identifier NCT00552058.

• Authors: W J Sandborn, S D Lee, C Randall, A Gutierrez, D A Schwartz, S Ambarkhane, C Kayhan, B Pierre-Louis, S Schreiber, G R Lichtenstein
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 40 Issue 8 Pg. 903-16 (Oct 2014) ISSN: 1365-2036 [Electronic] England
• PMID: 25146586 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunoglobulin Fab Fragments
• Immunosuppressive Agents
• Leukocyte L1 Antigen Complex
• Polyethylene Glycols
• C-Reactive Protein
• Certolizumab Pegol

Topics

• Adult
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• C-Reactive Protein (metabolism)
• Certolizumab Pegol
• Crohn Disease (drug therapy)
• Double-Blind Method
• Female
• Humans
• Immunoglobulin Fab Fragments (adverse effects, therapeutic use)
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Leukocyte L1 Antigen Complex (metabolism)
• Male
• Middle Aged
• Polyethylene Glycols (adverse effects, therapeutic use)
• Remission Induction
• Treatment Outcome