Edward V Loftus1, Jean-Frederic Colombel2, Stefan Schreiber3, Charles W Randall4, Miguel Regueiro5, Tauseef Ali6, Catherine Arendt7, Jason Coarse8, Marshall Spearman9, Gordana Kosutic8. 1. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: loftus.edward@mayo.edu. 2. Icahn School of Medicine at Mount Sinai, New York, New York. 3. Gastroenterology, Christian-Albrechts University at Kiel, Kiel, Germany. 4. Gastroenterology Research of America, San Antonio, Texas. 5. Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 6. College of Medicine - Gastroenterology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. 7. UCB Pharma, Brussels, Belgium. 8. UCB Pharma, Raleigh, North Carolina. 9. UCB Pharma, Smyrna, Georgia.
Abstract
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).
BACKGROUND & AIMS: 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 tumornecrosis factor, to quantify safety events in patients with CD. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).
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