title: Safety of Long-term Treatment With Certolizumab Pegol in Patients With Crohn's Disease, Based on a Pooled Analysis of Data From Clinical Trials.
abstract: Treatments for Crohn's disease (CD) have been linked to serious infections, malignancies, and dermatologic complications. We pooled and analyzed clinical trials of certolizumab pegol, a pegylated humanized Fab' fragment against tumor necrosis factor, to quantify safety events in patients with CD.
  
  
  
  We collected data from 5 placebo-controlled trials, 9 open-label studies, and 1 dose-regimen study, conducted globally through April 2014. A total of 2570 patients with moderate to severe CD were treated with certolizumab pegol, with 4378.1 patient-years of exposure. Data were analyzed in 2 groups: patients from placebo-controlled (PC) trials treated with placebo (n = 875) or certolizumab pegol (n = 919) for 6 to 38 weeks (the PC group) or all patients exposed to certolizumab pegol (n = 2570), for durations of 6 to 362 weeks (the all-studies group). Incidence rates (IRs; incidence/100 patient-years) of adverse events (AEs) were calculated from first dose through 70 days (approximately 5 half-lives) after the last dose.
  
  
  
  In the PC group, IRs for serious AEs were similar among patients given certolizumab pegol (31.35/100 patient-years) vs placebo (24.33/100 patient-years). IRs of serious infections or malignancies were low among patients receiving short-term treatment with certolizumab pegol (8.49/100 patient-years and 1.01/100 patient-years, respectively, in the PC group) and did not increase with long-term treatment (6.47/100 patient-years and 0.80/100 patient-years, respectively, in the all-studies group). IRs of psoriasis or psoriasiform dermatitis were low in the PC group (1.01/100 patient-years and 0/100 patient-years, respectively); in the placebo group, these IRs were 0.38 per 100 patient-years and 0 per 100 patient-years, respectively. IRs of psoriasis or psoriasiform dermatitis did not increase with long-term treatment (0.93/100 patient-years and 0.09/100 patient-years, respectively, in the all-studies group).
  
  
  
  Based on an analysis of data pooled from 15 trials of patients with CD, the safety profile for long-term therapy with certolizumab pegol therapy is similar to that reported from short-term studies. Overall rates of AEs, serious infections, malignancies, and psoriasis did not increase with long-term treatment, suggesting a favorable risk-benefit ratio with long-term certolizumab pegol therapy in CD. Clinicaltrials.gov identifiers: NCT00291668, NCT00152490, NCT00152425, NCT00308581, NCT00349752, NCT00552058, NCT00329550, NCT00329420, NCT00160524, NCT00160706, NCT00297648, NCT00333788, NCT00307931, NCT00356408, and NCT00552344 (https://www.clinicaltrials.gov/ct2/search).
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: loftus.edward@mayo.edu.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Gastroenterology, Christian-Albrechts University at Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Gastroenterology Research of America, San Antonio, Texas.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Randall
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Miguel
authors.initials: M
authors.lastname: Regueiro
authors.affiliation: College of Medicine - Gastroenterology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Tauseef
authors.initials: T
authors.lastname: Ali
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Arendt
authors.affiliation: UCB Pharma, Raleigh, North Carolina.
authors.forename: Jason
authors.initials: J
authors.lastname: Coarse
authors.affiliation: UCB Pharma, Smyrna, Georgia.
authors.forename: Marshall
authors.initials: M
authors.lastname: Spearman
authors.affiliation: UCB Pharma, Raleigh, North Carolina.
authors.forename: Gordana
authors.initials: G
authors.lastname: Kosutic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068582:Certolizumab Pegol / Q000009:adverse effects* / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D003424:Crohn Disease / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage
chemical_list: D007166:Immunosuppressive Agents; D010919:Placebos; D000068582:Certolizumab Pegol
keywords: Complication; Pooled Analysis; Side Effects; TNF