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. 1997 Feb;56(2):97–102. doi: 10.1136/ard.56.2.97

Study of eight cases of cancer in 426 rheumatoid arthritis patients treated with methotrexate

C Bologna 1, M Picot 1, C Jorgensen 1, P Viu 1, R Verdier 1, J Sany 1
PMCID: PMC1752316  PMID: 9068281

Abstract

OBJECTIVE—To report cancer cases in 426 rheumatoid arthritis patients treated with methotrexate, and determine whether there was an increased incidence of cancer compared with patients never treated with methotrexate (rheumatoid controls) and to the whole regional population.
METHODS—The duration of methotrexate treatment was 37.4 (SD 27.9) months. This population was compared with 420 rheumatoid arthritis controls and with a regional population of 812 344 people. Life table analysis was performed to compare the cancer incidence in the two rheumatoid populations. Adjustment for potentially confounding factors was done. The indirect standardisation method was used to compare each rheumatoid population with the regional population.
RESULTS—Eight cases of cancer (1.88%; 4.04 cases/1000 person years) were diagnosed in the methotrexate population v six (1.43%; 58.8 cases/1000 person years) in the rheumatoid controls. The life table method showed a higher incidence of cancer in the rheumatoid controls (P = 0.0001). In a multivariate analysis (Cox model), the only significant factor explaining this difference in the cancer incidence was age (P = 0.02). In the regional population there were 6418 new cases of cancer (0.79%; 2.85 cases/1000 person years). By the indirect standardisation method, the ratio of observed cases to expected cases of cancer in each of the rheumatoid populations was not significantly different from 1.
CONCLUSIONS—In these eight cases, methotrexate was not found to be responsible for generating cancers. However, because of data regarding lymphomas and methotrexate, and because of the short follow up, especially in the control group, longer prospective studies are warranted.



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Cancer-free survival curves (event = occurrence of a cancer) in the two rheumatoid populations: treated with methotrexate (n = 426) and controls never treated with methotrexate (n = 420). The difference between the curves is significant (P = 0.0001, log-rank), indicating a higher occurrence of cancers in the rheumatoid controls.

Selected References

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