title: Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease.
abstract: We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality.
  
  
  
  Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ.
  
  
  
  The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates.
  
  
  
  This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.
authors: University of Nebraska Medical Center, Omaha, Nebraska, USA National Data Bank for Rheumatic Diseases, Wichita, Kansas, USA.
authors: Kaleb
authors: 0000-0002-5350-3934
authors: K
authors: Michaud
authors: Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors: Niklas
authors: N
authors: Berglind
authors: Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors: Stefan
authors: S
authors: Franzén
authors: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Thomas
authors: 0000-0002-5735-9626
authors: T
authors: Frisell
authors: Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK.
authors: Christopher
authors: C
authors: Garwood
authors: NYU School of Medicine, New York, New York, USA Corrona LLC, Southborough, Massachusetts, USA.
authors: Jeffrey D
authors: JD
authors: Greenberg
authors: Clinical, Global Medicines Development, AstraZeneca R&D, Macclesfield, UK.
authors: Meilien
authors: M
authors: Ho
authors: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Marie
authors: M
authors: Holmqvist
authors: Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca, Wilmington, Delaware, USA.
authors: Laura
authors: L
authors: Horne
authors: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Eisuke
authors: E
authors: Inoue
authors: Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors: Fredrik
authors: 0000-0003-0892-5668
authors: F
authors: Nyberg
authors: Corrona LLC, Southborough, Massachusetts, USA The College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA.
authors: Dimitrios A
authors: DA
authors: Pappas
authors: Corrona LLC, Southborough, Massachusetts, USA University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors: George
authors: G
authors: Reed
authors: Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Deborah
authors: 0000-0002-8625-1200
authors: D
authors: Symmons
authors: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Eiichi
authors: E
authors: Tanaka
authors: MedImmune, Gaithersburg, Maryland, USA.
authors: Trung N
authors: TN
authors: Tran
authors: Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK.
authors: Suzanne M M
authors: SM
authors: Verstappen
authors: Patient Safety, GRAPSQA, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors: Eveline
authors: E
authors: Wesby-van Swaay
authors: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Hisashi
authors: H
authors: Yamanaka
authors: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
authors: Johan
authors: J
authors: Askling
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D015982:Bias; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D007843:Latin America / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D009656:North America / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012042:Registries / Q000706:statistics & numerical data*; D013548:Sweden / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents
keywords: Cardiovascular Disease; Epidemiology; Outcomes research; Rheumatoid Arthritis