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How comparable are rates of malignancies in patients with rheumatoid arthritis across the world? A comparison of cancer rates, and means to optimise their comparability, in five RA registries
  1. Johan Askling1,2,
  2. Niklas Berglind3,
  3. Stefan Franzen3,
  4. Thomas Frisell1,
  5. Christopher Garwood4,
  6. Jeffrey D Greenberg5,6,
  7. Meilien Ho7,
  8. Marie Holmqvist1,
  9. Laura Horne8,
  10. Eisuke Inoue9,
  11. Kaleb Michaud10,11,
  12. Fredrik Nyberg12,13,
  13. Dimitrios A Pappas14,
  14. George Reed15,
  15. Eiichi Tanaka9,
  16. Trung N Tran16,
  17. Suzanne M M Verstappen4,
  18. Hisashi Yamanaka9,
  19. Eveline Wesby-van Swaay17,
  20. Deborah Symmons4,18
  1. 1Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  3. 3Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  4. 4Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK
  5. 5NYU School of Medicine, New York, New York, USA
  6. 6Corrona LLC, Southborough, Massachusetts, USA
  7. 7Clinical, Global Medicines Development, AstraZeneca R&D, Macclesfield, UK
  8. 8Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca R&D, Wilmington, Delaware, USA
  9. 9Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan
  10. 10National Data Bank for Rheumatic Diseases, Wichita, Kansas, USA
  11. 11Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
  12. 12Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  13. 13Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  14. 14Columbia University College of Physicians and Surgeons, New York, New York, USA
  15. 15University of Massachusetts Medical School, Worcester, Massachusetts, USA
  16. 16MedImmune, Gaithersburg, Maryland, USA
  17. 17Patient Safety, GRAPSQA, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  18. 18NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  1. Correspondence to Professor Johan Askling, Department of Medicine Solna, Karolinska Institutet, Clinical Epidemiology Unit M9:01, Stockholm SE-171 77, Sweden; johan.askling{at}


Background The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents.

Methods Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib).

Results There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis.

Conclusion In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.

  • Rheumatoid Arthritis
  • Epidemiology
  • Outcomes research

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