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Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease
  1. Kaleb Michaud1,2,
  2. Niklas Berglind3,
  3. Stefan Franzén3,
  4. Thomas Frisell4,
  5. Christopher Garwood5,
  6. Jeffrey D Greenberg6,7,
  7. Meilien Ho8,
  8. Marie Holmqvist4,
  9. Laura Horne9,
  10. Eisuke Inoue10,
  11. Fredrik Nyberg11,12,
  12. Dimitrios A Pappas7,13,
  13. George Reed7,14,
  14. Deborah Symmons5,15,
  15. Eiichi Tanaka10,
  16. Trung N Tran16,
  17. Suzanne M M Verstappen5,
  18. Eveline Wesby-van Swaay17,
  19. Hisashi Yamanaka10,
  20. Johan Askling4,18
  1. 1University of Nebraska Medical Center, Omaha, Nebraska, USA
  2. 2National Data Bank for Rheumatic Diseases, Wichita, Kansas, USA
  3. 3Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  4. 4Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  5. 5Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK
  6. 6NYU School of Medicine, New York, New York, USA
  7. 7Corrona LLC, Southborough, Massachusetts, USA
  8. 8Clinical, Global Medicines Development, AstraZeneca R&D, Macclesfield, UK
  9. 9Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca, Wilmington, Delaware, USA
  10. 10Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
  11. 11Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  12. 12Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  13. 13The College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, USA
  14. 14University of Massachusetts Medical School, Worcester, Massachusetts, USA
  15. 15NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  16. 16MedImmune, Gaithersburg, Maryland, USA
  17. 17Patient Safety, GRAPSQA, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  18. 18Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to Dr Kaleb Michaud, Department of Medicine, University of Nebraska Medical Center, 986270 Nebraska Medical Center, Omaha NE 68198-6270, USA; kmichaud{at}unmc.edu

Abstract

Background 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.

Methods 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.

Results 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.

Conclusions 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.

  • Rheumatoid Arthritis
  • Cardiovascular Disease
  • Outcomes research
  • Epidemiology

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