title: Lymphoma and luekemia in rheumatoid arthritis: are they associated with azathioprine, cyclophosphamide, or methotrexate?
abstract: Incident cases of lymphoma and leukemia in a cohort of 3824 rheumatoid arthritis (RA) patients from the Arthritis, Rheumatism and Aging Medical Information System (ARAMIS) database were identified, and the use of azathioprine, cyclophosphamide, and methotrexate was compared in a matched case-control study. Controls were matched on age, sex, year of study entry, disease duration, center, and years of follow-up. Twenty-four cases of lymphoma and 10 cases of leukemia were identified: 21% of patients with cancer versus 9% of controls had taken azathioprine [McNemar statistic 1.50 (p = 0.22), odds ratio 5.0 (95% confidence interval 0.6,236.5)]. Equal numbers of cases and controls (6% each) had taken cyclophosphamide and 18% of cases and 12% of controls had taken methotrexate [McNemar statistic 0.13 (p = 0.72), odds ratio 1.7 (0.3, 10.7)]. Results suggest but do not prove that RA patients taking azathioprine and methotrexate may have an increased risk of developing lymphoma. However, even if this increased risk can be confirmed, it accounts for only a small proportion of the greatly increased incidence of these malignancies in RA.
authors.affiliation: BRI International, Inc. (C.A.W.); Department of Medicine (J.F.F., G.S.)/Division of Immunology and Rheumatology and Division of Biostatistics (D.A.B.), Stanford University; University of Saskatchewan, Saskatoon, Canada (J.S., M.H.); Arthritis Center, Wichita, Kansas (F.W.); private practice, Montreal, Canada (J.-P.R.); and Glaxo Wellcome (Research Triangle Park, NC) (A.R.H.).
authors.forename: C A
authors.initials: CA
authors.lastname: Williams
authors.forename: D A
authors.initials: DA
authors.lastname: Bloch
authors.forename: J
authors.initials: J
authors.lastname: Sibley
authors.forename: M
authors.initials: M
authors.lastname: Haga
authors.forename: F
authors.initials: F
authors.lastname: Wolfe
authors.forename: J P
authors.initials: JP
authors.lastname: Raynauld
authors.forename: G
authors.initials: G
authors.lastname: Singh
authors.forename: A R
authors.initials: AR
authors.lastname: Hickey
authors.forename: J F
authors.initials: JF
authors.lastname: Fries