title: Safety Profile of Certolizumab Pegol in Patients with Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Alice
authors: A
authors: Capogrosso Sansone
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.|Pharmaceutical Unit, Health District of Lucca, Lucca, Italy.
authors: Stefania
authors: S
authors: Mantarro
authors: Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy. marco.tuccori@gmail.com.|Tuscan Regional Centre for Pharmacovigilance, Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Via Roma, 55, 56126, Pisa, Italy. marco.tuccori@gmail.com.
authors: Marco
authors: M
authors: Tuccori
authors: Pharmaceutical Unit, Health District of Pisa, Pisa, Italy.
authors: Elisa
authors: E
authors: Ruggiero
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Sabrina
authors: S
authors: Montagnani
authors: Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy.
authors: Irma
authors: I
authors: Convertino
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Alessandra
authors: A
authors: Marino
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Matteo
authors: M
authors: Fornai
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Luca
authors: L
authors: Antonioli
authors: Pharmaceutical Unit, Health District of Pisa, Pisa, Italy.
authors: Tiberio
authors: T
authors: Corona
authors: Pharmaceutical Unit, Health District of Lucca, Lucca, Italy.
authors: Danila
authors: D
authors: Garibaldi
authors: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.|Unit of Adverse Drug Reaction Monitoring, University Hospital of Pisa, Pisa, Italy.
authors: Corrado
authors: C
authors: Blandizzi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000068582:Certolizumab Pegol / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol