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Safety Profile of Certolizumab Pegol in Patients with Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis

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Abstract

Introduction

Certolizumab pegol (CZP), an anti-tumor necrosis factor PEGylated Fab’ fragment of a humanized monoclonal antibody, is currently approved for treatment of some immune-mediated inflammatory diseases (IMIDs). To our knowledge, no systematic review and meta-analysis evaluating the overall safety profile of CZP has been performed.

Objective

The objective of this systematic review was to assess the adverse event (AE) patterns of CZP versus a control in patients with IMIDs.

Methods

A systematic literature search was performed using PubMed/MEDLINE, EMBASE, the Cochrane Library, and the FDA database for clinical trials up to March 2014. Eligible studies were those that compared the safety profile of CZP to a control group in patients with IMIDs. The following data were extracted: number of patients experiencing AEs, serious AEs (SAEs), adverse drug reactions (ADRs), withdrawals due to AEs, fatal AEs, infectious AEs and SAEs, upper respiratory tract infections, injection-site reactions, neoplasms, and tuberculosis.

Results

A total of 2023 references were identified and 18 randomized controlled trials were included. The main pooled risk ratios of CZP-treated versus control patients were as follows: AEs 1.09 (95 % confidence interval, CI 1.04–1.14), SAEs 1.50 (95 % CI 1.21–1.86), ADRs 1.20 (95 % CI 1.03–1.39), infectious AEs 1.28 (95 % CI 1.13–1.45), infectious SAEs 2.17 (95 % CI 1.36–3.47), and upper respiratory tract infections 1.34 (95 % CI 1.15–1.57).

Conclusion

Safety data on CZP suggest an overall favorable tolerability profile, with infections being the most common AE. However, CZP-treated patients had a twofold higher risk of infectious SAEs than control patients. Large observational studies and data from national registries are needed to detect rare AEs, which might occur after long-term exposures to CZP.

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Acknowledgments

The authors gratefully acknowledge Dr. Stefano Salvadori (ScD, PhD, Institute of Clinical Physiology, National Research Council, Pisa, Italy) for his invaluable statistical support in the performance of meta-regression analysis.

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Correspondence to Marco Tuccori.

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Funding and conflict of interest

No sources of funding were used to assist in the preparation of this study. Alice Capogrosso Sansone, Stefania Mantarro, Marco Tuccori, Elisa Ruggiero, Sabrina Montagnani, Irma Convertino, Alessandra Marino, Matteo Fornai, Luca Antonioli, Tiberio Corona, Danila Garibaldi, and Corrado Blandizzi have no conflicts of interest that are directly relevant to the content of this study.

Additional information

A. Capogrosso Sansone and S. Mantarro contributed equally to this work.

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Capogrosso Sansone, A., Mantarro, S., Tuccori, M. et al. Safety Profile of Certolizumab Pegol in Patients with Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis. Drug Saf 38, 869–888 (2015). https://doi.org/10.1007/s40264-015-0336-2

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