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Rheumatoid arthritis
Original article
Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme
  1. Hisashi Yamanaka1,
  2. Johan Askling2,3,
  3. Niklas Berglind4,
  4. Stefan Franzen4,
  5. Thomas Frisell2,
  6. Christopher Garwood5,
  7. Jeffrey D Greenberg6,7,
  8. Meilien Ho8,
  9. Marie Holmqvist2,
  10. Laura Novelli Horne9,
  11. Eisuke Inoue1,
  12. Kaleb Michaud10,11,
  13. Dimitrios A Pappas7,12,
  14. George Reed7,13,
  15. Deborah Symmons5,14,
  16. Eiichi Tanaka1,
  17. Trung N Tran15,
  18. Suzanne M M Verstappen5,
  19. Eveline Wesby-van Swaay16 and
  20. Fredrik Nyberg17,18
  1. 1Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
  2. 2Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
  4. 4Biometric & Information Sciences, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  5. 5Arthritis Research UK Centre for Epidemiology, The University of Manchester, Manchester, UK
  6. 6NYU School of Medicine, New York City, New York, USA
  7. 7Corrona LLC, Southborough, Massachusetts, USA
  8. 8Clinical, Global Medicines Development, AstraZeneca R&D, Alderley Park, Macclesfield, UK
  9. 9Medical Evidence & Observational Research Centre, Global Medical Affairs, AstraZeneca, Wilmington, Delaware, USA
  10. 10University of Nebraska Medical Center, Omaha, Nebraska, USA
  11. 11National Data Bank for Rheumatic Diseases, Wichita, Kansas, USA
  12. 12The College of Physicians and Surgeons, Columbia University, New York City, New York, USA
  13. 13University of Massachusetts Medical School, Worcester, Massachusetts, USA
  14. 14NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
  15. 15MedImmune, Gaithersburg, Maryland, USA
  16. 16Patient Safety, GRAPSQA, Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden
  17. 17Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  18. 18Medical Evidence & Observational Research Centre, Global Medical Affairs, AstraZeneca R&D, Mölndal, Sweden
  1. Correspondence to Dr Hisashi Yamanaka; yamanaka{at}twmu.ac.jp, hisashi{at}pc4.so-net.ne.jp

Abstract

Objective Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population.

Methods We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score.

Results Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14–1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86–2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99–2.84, trials rate 2.74).

Conclusion This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries.

  • rheumatoid arthritis
  • epidemiology
  • infections
  • outcomes research

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/rmdopen-2017-000498

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    Footnotes

    • Contributors All authors were involved in the conception and design of the study and/or analyses. All authors were involved in the data analysis of each cohort and were involved in data interpretation. Drafting of this paper is mainly by HY and FN, but all authors were involved in critically reviewing the manuscript, and all authors read and approved the final version.

    • Funding AstraZeneca funded this study and collaborated with the researchers in the design, analysis and interpretation. Five independent registries have own funding support, but those funding sources are not involved in the design, analysis of this study. NOAR is funded by Arthritis Research UK. SRR has or has had research agreements with AbbVie, Pfizer, BMS, UCB, Merck, AstraZeneca, Sobi, and Roche. IORRA is supported by various grants from a large number of pharmaceutical companies, including AstraZeneca. CORRONA Inc. has received funding in the past 2 years from AbbVie, Amgen, AstraZeneca, Janssen, Genentech, Lilly, Novartis, Pfizer, Regeneron, Vertex and UCB, through contracted subscriptions to the database, and CORRONA International LLC has received funding from AstraZeneca.

    • Competing interests FN, NB, TNT, EW-vS and MeH are employees of AstraZeneca. FN, NB, LH, TNT, EW-vS, MeH and SF hold AstraZeneca stocks and/or options. LH and SF were employees of AstraZeneca during the time in which the research was conducted, and CG was affiliated with the Arthritis Research UK Centre for Epidemiology. JA has had grant/research support from AstraZeneca and has been a consultant for AstraZeneca. TF has received honoraria for advisory board participation from Pfizer. JDG is a shareholder of CORRONA, Inc., and has consulted for AstraZeneca, CORRONA, Novartis and Pfizer. DAP is an employee of CORRONA and has been a paid instructor for Novartis. GR is an employee of CORRONA. KM has grant/research support from ACR Rheumatology Research Foundation and is codirector of the National Data Bank for Rheumatic Diseases (NDB), which has received funds from AstraZeneca. HY leads the IORRA cohort and has been a consultant for AstraZeneca. DS has had grant/research support from AstraZeneca and has been a consultant for AstraZeneca.

    • Ethics approval Ethics committee/institutional review board of each institution.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement None.