title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Askling
authors.affiliation: Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Berglind
authors.affiliation: Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Franzen
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0002-5735-9626
authors.initials: T
authors.lastname: Frisell
authors.affiliation: Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Garwood
authors.affiliation: NYU School of Medicine, New York, New York, USA Corrona LLC, Southborough, Massachusetts, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
authors.affiliation: Clinical, Global Medicines Development, AstraZeneca R&D, Macclesfield, UK.
authors.forename: Meilien
authors.initials: M
authors.lastname: Ho
authors.affiliation: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Holmqvist
authors.affiliation: Medical Evidence & Observational Research Centre, Global Medicines Development, AstraZeneca R&D, Wilmington, Delaware, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Horne
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Inoue
authors.affiliation: National Data Bank for Rheumatic Diseases, Wichita, Kansas, USA Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Kaleb
authors.identifier: http://orcid.org/0000-0002-5350-3934
authors.initials: K
authors.lastname: Michaud
authors.affiliation: 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.forename: Fredrik
authors.identifier: http://orcid.org/0000-0003-0892-5668
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Pappas
authors.affiliation: University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: George
authors.initials: G
authors.lastname: Reed
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Trung N
authors.initials: TN
authors.lastname: Tran
authors.affiliation: Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK.
authors.forename: Suzanne M M
authors.initials: SM
authors.lastname: Verstappen
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Patient Safety, GRAPSQA, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Eveline
authors.initials: E
authors.lastname: Wesby-van Swaay
authors.affiliation: 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.forename: Deborah
authors.identifier: http://orcid.org/0000-0002-8625-1200
authors.initials: D
authors.lastname: Symmons
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008223:Lymphoma / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology; D009656:North America / Q000453:epidemiology; D012042:Registries / Q000706:statistics & numerical data*; D013548:Sweden / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
keywords: Epidemiology; Outcomes research; Rheumatoid Arthritis