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Extended report
Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project
  1. Louise K Mercer1,
  2. Anne C Regierer2,
  3. Xavier Mariette3,
  4. William G Dixon1,
  5. Eva Baecklund4,
  6. Karin Hellgren5,
  7. Lene Dreyer6,7,
  8. Merete Lund Hetland8,9,
  9. René Cordtz6,7,
  10. Kimme Hyrich1,10,
  11. Anja Strangfeld2,
  12. Angela Zink2,11,
  13. Helena Canhao12,
  14. M Victoria Hernandez13,
  15. Florence Tubach14,
  16. Jacques-Eric Gottenberg15,
  17. Jacques Morel16,
  18. Jakub Zavada17,
  19. Florenzo Iannone18,
  20. Johan Askling5,
  21. Joachim Listing2
  1. 1Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, UK
  2. 2Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany
  3. 3Department of Rheumatology, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, Le Kremlin Bicêtre, Paris, France
  4. 4Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  5. 5Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
  6. 6Center for Rheumatology and Spine Diseases, Gentofte University Hospital, Rigshospitalet, Hellerup, Denmark
  7. 7The Parker Institute, Frederiksberg, Denmark
  8. 8DANBIO, Copenhagen Center for Arthritis Research, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark
  9. 9Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  10. 10Musculoskeletal Biomedical Research Unit, National Institute of Health Research Manchester, Central Manchester NHS Foundation Trust, Manchester Academic Health Science, Manchester, UK
  11. 11CharitéUniversitätsmedizin Berlin, Berlin, Germany
  12. 12EpiDoC Unit, Universidade Nova de Lisboa, CEDOC, NOVA Medical School and National School of Public Health, Lisbon, Portugal
  13. 13Department of Rheumatology, Hospital Clinic of Barcelona, Barcelona, Spain
  14. 14Département of BIOSPIM, Département BIOSPIM Hôpital Pitié-Salpétrière, AP-HP, Sorbonne Universités, Université Pierre et Marie Curie, Paris, France
  15. 15Department of Rheumatology, CHU Strasbourg, Strasbourg, France
  16. 16Department of Rheumatology, University of Montpellier and Teaching Hospital Lapeyronie, Montpellier, France
  17. 17Institute of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
  18. 18Rheumatology Unit, University of Bari, Bari, Italy
  1. Correspondence to Dr Anne C Regierer, Deutsches Rheuma-Forschungszentrum Berlin, Ein Leibniz Institut, Programmbereich Epidemiologie, Charitéplatz 1, 10117 Berlin, Germany; Anne.Regierer{at}


Background Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.

Methods Patients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.

Results Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.

Conclusion This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

  • rheumatoid arthritis
  • DMARDs(biologic)
  • anti-TNF
  • epidemiology

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  • LKM and ACR contributed equally.

  • Contributors Study concept and design: LKM and JL. Acquisition of data and critical revision of the manuscript for important intellectual content: LKM, AR, XM, WGD, EB, KH, LD, MLH, RC, KH, AS, AZ, HC, MVH, FT, JEG, JM, JZ, FI, JA and JL. Drafting the manuscript: LKM, AR and JL. Final approval of the version published: LKM, AR, XM, WGD, EB, KH, LD, MLH, RC, KH, AS, AZ, HC, MVH, FT, JEG, JM, JZ, FI, JA and JL.

  • Funding Individual registries had entered into agreements with pharmaceutical companies (AbbVie, BMS, Hospira, MSD, Pfizer, Roche, UCB, Samsung and Eli Lilly). The pharmaceutical companies funding these registers were, however, not involved in the planning of the project, the statistical analyses, the interpretation of the results or the decision to publish.

  • Competing interests AR received speaker fees (less than $10 000) from Celgene and Janssen. XM received honorarium (less than $10 000) from BMS, Pfizer and UCB. LD has received speaker fees from UCB and MSD. KH received grant/research support from Pfizer and honoraria (less than $10 000) from Abbvie and Pfizer. AS received speaker fees (less than $10 000) from BMS, MSD, Pfizer, Roche and Sanofi-Aventis. AZ received grant/research support from Abbvie, Amgen, BMS, MSD, Roche, Pfizer and UCB for the German biologics register RABBIT and speaker fees (less than $10 000) from BMS, MSD, Novartis, Pfizer, Roche, Sanofi and UCB. JEG received honorarium (less than $10 000) from Abbvie, BMS, MSD, Pfizer, Roche and UCB. JM received less than $10 000 for honoraria and consultancies from Roche. JZ received honorarium (less than $10 000) from Abbvie and Hospira. FI received personal fees from Actelion, Celgene, Janssen, Pfizer, AbbVie, UCB and MSD outside the submitted work. JA received grant/research support from AstraZeneca, Merck, Lilly and Pfizer, and has received grant support from Abbvie, Pfizer, Merck, Roche, BMS and UCB for the ARTIS register. JL received honoraria (less than $10 000) from Novartis-Sandoz and Pfizer.

  • Patient consent Obtained.

  • Ethics approval Local ethics committee.

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

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