PMID- 27464588 OWN - NLM STAT- MEDLINE DCOM- 20170809 LR - 20180927 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 14 IP - 12 DP - 2016 Dec TI - Safety of Long-term Treatment With Certolizumab Pegol in Patients With Crohn's Disease, Based on a Pooled Analysis of Data From Clinical Trials. PG - 1753-1762 LID - S1542-3565(16)30440-2 [pii] LID - 10.1016/j.cgh.2016.07.019 [doi] AB - 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). CI - Copyright (c) 2016 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Loftus, Edward V Jr AU - Loftus EV Jr AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: loftus.edward@mayo.edu. FAU - Colombel, Jean-Frederic AU - Colombel JF AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Schreiber, Stefan AU - Schreiber S AD - Gastroenterology, Christian-Albrechts University at Kiel, Kiel, Germany. FAU - Randall, Charles W AU - Randall CW AD - Gastroenterology Research of America, San Antonio, Texas. FAU - Regueiro, Miguel AU - Regueiro M AD - Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. FAU - Ali, Tauseef AU - Ali T AD - College of Medicine - Gastroenterology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. FAU - Arendt, Catherine AU - Arendt C AD - UCB Pharma, Brussels, Belgium. FAU - Coarse, Jason AU - Coarse J AD - UCB Pharma, Raleigh, North Carolina. FAU - Spearman, Marshall AU - Spearman M AD - UCB Pharma, Smyrna, Georgia. FAU - Kosutic, Gordana AU - Kosutic G AD - UCB Pharma, Raleigh, North Carolina. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160725 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Immunosuppressive Agents) RN - 0 (Placebos) RN - UMD07X179E (Certolizumab Pegol) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Certolizumab Pegol/*adverse effects/*therapeutic use MH - Controlled Clinical Trials as Topic MH - Crohn Disease/*drug therapy MH - Drug-Related Side Effects and Adverse Reactions/*epidemiology/pathology MH - Female MH - Humans MH - Immunosuppressive Agents/*adverse effects/*therapeutic use MH - Incidence MH - Male MH - Middle Aged MH - Placebos/administration & dosage OTO - NOTNLM OT - Complication OT - Pooled Analysis OT - Side Effects OT - TNF EDAT- 2016/07/29 06:00 MHDA- 2017/08/10 06:00 CRDT- 2016/07/29 06:00 PHST- 2015/12/18 00:00 [received] PHST- 2016/07/07 00:00 [revised] PHST- 2016/07/10 00:00 [accepted] PHST- 2016/07/29 06:00 [pubmed] PHST- 2017/08/10 06:00 [medline] PHST- 2016/07/29 06:00 [entrez] AID - S1542-3565(16)30440-2 [pii] AID - 10.1016/j.cgh.2016.07.019 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2016 Dec;14(12):1753-1762. doi: 10.1016/j.cgh.2016.07.019. Epub 2016 Jul 25.