Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis

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 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.

Association of Higher Methotrexate Dose With Lymphoproliferative Disease Onset in Rheumatoid Arthritis Patients

“…The following parameters were examined in the MTX non-LPD group and the MTX-LPD group: 1) age at RA onset, 2) RA disease duration, 3) joint destruction estimated using the Steinbrocker classification, 4) medications other than MTX, 5) corticosteroid treatment, 6) treatment with biologic agents, 7) age at MTX initiation, 8) mean MTX dose, 9) total MTX dose, and 10) complications of Sjögren's syndrome. When the relative risk of LPD including malignant lymphoma was estimated as being 4.0, in agreement with Baecklund et al (11), and the number of case-control sets was 20, the relative power for 4 controls per case was estimated as being approximately 62% (12). A comparison of parameters between the 2 groups was undertaken using an unpaired t-test, chisquare test, covariance analysis, and logistic regression analysis with StatView, version 5.0 (SAS).…”

“…The frequencies of MTX-LPD in our patients and the reports from other countries were 0.5% and 0.05-0.3%, respectively, which are quite similar (5,11). However, the mean MTX dose showed a significant difference between the LPD and the non-LPD group in our study.…”

“…We speculate that the reasons for this discrepancy are related to racial differences between our Japanese patients and the previously reported Western patients. Although several previous studies have reported that high RA disease activity is related to the onset of RA-MTX-LPD and RA-LPD (11,13), there is a study that reported the development of LPD in RA patients even with low disease activity (15). Regarding RA disease activity at MTX-LPD onset in our patients, the median DAS28-CRP was 2.26 (IQR 2.09 -2.82), which indicated low disease activity.…”

Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis

“…A reappraisal of RA disease manifestations over the last decade has emphasized the expanding spectrum of the rheumatoid syndrome, which now includes accelerated cardiovascular disease as well as increased susceptibility to lymphoma and infection (1)(2)(3). Although the broad use of immunosuppressants makes it difficult to distinguish between iatrogenic and disease-intrinsic pathogenic factors, it is clear that the overall immunocompetence of RA patients is compromised (4).…”

Lymphoma in rheumatoid arthritis: An immune system set up for failure

“…This question of whether lymphoma in RA may result from insufficient or too-aggressive immunosuppressive therapy has been addressed in an elegant study by Baecklund and colleagues, reported elsewhere in this issue of Arthritis & Rheumatism (14). By making use of unique patient and tissue registries in Sweden and tracking large cohorts of RA patients over decades, those researchers identified 378 consecutive cases with RA and subsequent malignant lymphoma and compared them with 378 control patients from a population-based cohort of 74,651 Swedes followed up for the diagnosis of RA.…”