The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation.
OBJECTIVE
To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup.


METHODS
Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates.


RESULTS
Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma.


CONCLUSIONS
In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.
Wolfe
Frederick
F
National Data Bank for Rheumatic Diseases, Wichita, KS 67214, USA. fwolfe@arthritis-research.org
Michaud
Kaleb
K
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008137:Longitudinal Studies; D008223:Lymphoma / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D018426:SEER Program; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate