TY - JOUR
T1 - Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn's disease
T2 - A pooled analysis of 11 317 patients across clinical trials
AU - Curtis, Jeffrey R.
AU - Mariette, Xavier
AU - Gaujoux-Viala, Cécile
AU - Blauvelt, Andrew
AU - Kvien, Tore K.
AU - Sandborn, William J.
AU - Winthrop, Kevin
AU - De Longueville, Marc
AU - Huybrechts, Ivo
AU - Bykerk, Vivian P.
N1 - Funding Information:
Competing interests Jrc: grant/research and consultancy fees from abbVie, amgen, Bristol-Myers Squibb, corrona, crescendo, genentech, Janssen, roche, Pfizer and UcB Pharma. XM: consultant for Bristol-Myers Squibb, glaxoSmithKline, Janssen, lFB Pharmaceuticals, Pfizer and UcB Pharma. grant/research support from: Biogen, Pfizer and UcB Pharma. cgV: Speaking and/or consulting fees from abbVie, amgen, Bristol-Myers Squibb, celgene, eli lilly, gilead, Janssen, Merck-Serono, Medac, nordic Pharma, novartis, Pfizer, roche, Sandoz, Sanofi and UcB Pharma. aB: consulting honoraria and clinical investigator: abbVie, aclaris, akros, allergan, almirall, amgen, arena, Boehringer ingelheim, Bristol-Myers Squibb, celgene, Dermavant, Dermira inc., eli lilly, genentech/roche, glaxoSmithKline, Janssen, leo, Meiji, Merck, novartis, Pfizer, Purdue Pharma, regeneron, revance, Sandoz, Sanofi genzyme, Sienna Pharmaceuticals, Sun Pharma, UcB Pharma, Valeant and Vidac. tKK: Speaking and/or consulting fees from Biogen, Bristol-Myers Squibb, Boehringer ingelheim, celltrion, eli lilly, epirus, Hospira, Merck-Serono, novartis, Orion Pharma, Pfizer, Sandoz and UcB Pharma. WJS: research grants from atlantic Healthcare limited, abbVie, amgen, celgene/receptos, genentech, eli lilly, gilead Sciences, Janssen and takeda; consulting fees from abbVie, allergan, amgen, Boehringer ingelheim, celgene, conatus, cosmo, eli lilly, escalier Biosciences, Ferring, genentech, gilead, gossamer Bio, Janssen, Miraca life Sciences, nivalis therapeutics, novartis nutrition Science Partners, Oppilan Pharma, Otsuka, Paul Hastings, Pfizer, Precision iBD, Progenity, Prometheus laboratories, ritter Pharmaceuticals, robarts clinical trials (owned by Health academic research trust or Hart), Salix, Shire, Seres therapeutics, Sigmoid Biotechnologies, takeda, tigenix, tillotts Pharma, UcB Pharma and Vivelix; Stock options from escalier Biosciences, gossamer Bio, Oppilan Pharma, Precision iBD, Progenity and ritter Pharmaceuticals. KW: consultant fees from abbVie, Bristol-Myers Squibb, eli lilly, Pfizer, roche and UcB Pharma. Mdl: employee of UcB Pharma. iH: employee of UcB Pharma. VPB: consulting fees from abbVie, amgen, Bristol-Myers Squibb, genentech, Pfizer, regeneron, Scipher and UcB Pharma.
Funding Information:
Acknowledgements this study, including medical writing and editorial assistance, was funded by UcB Pharma. the authors thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. the authors also acknowledge Pauline ralston, MSc, and nicola tilt, MSc, UcB Pharma, Brussels, Belgium, for statistical assistance, christina Popova, MD, and catherine arendt, MD, PharmD, UcB Pharma, Brussels, Belgium, for assistance with medical review of adverse events, plus Debbie nixon, DPhil, UcB Pharma, UK, for publication coordination and lucy Berry, MBBS, and emma Phillips, PhD, costello Medical, UK, for medical writing and editorial assistance.
Publisher Copyright:
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Objective To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.
AB - Objective To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.
KW - ankylosing spondylitis
KW - anti-TNF
KW - dmards (biologic)
KW - psoriatic arthritis
KW - rheumatoid arthritis
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U2 - 10.1136/rmdopen-2019-000942
DO - 10.1136/rmdopen-2019-000942
M3 - Article
AN - SCOPUS:85067047883
SN - 2056-5933
VL - 5
JO - RMD Open
JF - RMD Open
IS - 1
M1 - e000942
ER -