RESEARCH - Association of chronic inflammation, not its treatment, with increased lymphoma risk in RA

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Arthritis & Rheumatism

Volume 54 Issue 3, Pages 692 - 701

Published Online: 28 Feb 2006

Association of chronic inflammation, not its treatment, with increased

lymphoma risk in rheumatoid arthritis

Eva Baecklund 1 *, Anastasia Iliadou 2, Johan Askling 2, Anders Ekbom

3 6, Carin Backlin 4, Fredrik Granath 2, Anca Irinel Catrina 2,

Rosenquist 4, Nils Feltelius 5, Christer Sundström 4, Lars

Klareskog 2

1Akademiska Hospital, Uppsala, Sweden

2Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

3Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

4Uppsala University, Uppsala, Sweden

5Karolinska Institutet, Karolinska University Hospital, Stockholm, and

Swedish Medical Products Agency, Uppsala, Sweden

6Harvard School of Public Health, Boston, Massachusetts

Abstract

Objective

Chronic inflammatory conditions such as rheumatoid arthritis (RA) have

been associated with malignant lymphomas. This study was undertaken to

investigate which patients are at highest risk, and whether

antirheumatic treatment is hazardous or protective.

Methods

We performed a matched case-control study of 378 consecutive Swedish

RA patients in whom malignant lymphoma occurred between 1964 and 1995

(from a population-based RA cohort of 74,651 RA patients), and 378

controls. Information on disease characteristics and treatment from

onset of RA until lymphoma diagnosis was abstracted from medical

records. Lymphoma specimens were reclassified and tested for

Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for

lymphomas (by subtype) associated with deciles of cumulative disease

activity were assessed, as were ORs associated with drug treatments.

Results

The relative risks of lymphoma were only modestly elevated up to the

seventh decile of cumulative disease activity. Thereafter, the

relative risk increased dramatically (OR ninth decile 9.4 [95%

confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence

interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large

B cell type, but other lymphoma subtypes also displayed an association

with cumulative disease activity. Standard nonbiologic treatments did

not increase lymphoma risk. EBV was present in 12% of lymphomas.

Conclusion

Risk of lymphoma is substantially increased in a subset of patients

with RA, those with very severe disease. High inflammatory activity,

rather than its treatment, is a major risk determinant.

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