Epidemiology
Cancer in Rheumatoid Arthritis: Occurrence, Mortality, and Associated Factors in a South European Population

https://doi.org/10.1016/j.semarthrit.2007.08.006Get rights and content

Objectives

To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA).

Methods

We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI).

Results

The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)).

Conclusions

The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.

Section snippets

Patients

The EMECAR cohort (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) was designed to assess the burden of comorbidity and inflammatory activity in RA and has been described in detail elsewhere (28). In summary, the cohort comprises a random sample of patients fulfilling the American College of Rheumatology classification criteria for RA, selected from the administrative databases of 34 centers. Patients who had been selected but who could not be contacted were substituted

Characteristics of the Study Population

The study started in March 1999 and ended in June 2005; the total follow-up was 2269 person-years, and the median per-patient follow-up was 3.95 years (25th to 75th percentiles (P25-75): 2.1-4.1 years) with a maximum of 6.04 years. Patient demographic and clinical baseline characteristics of the cohort, including medication use, are summarized in Table 1. The sample was composed mainly of women in their sixties (median: 64 (P25-75: 54-71)) with longstanding RA, as the mean disease duration was

Discussion

In this representative cohort of Spanish RA patients, we have not demonstrated an increase in overall cancer incidence compared with the expected rate of cancer in the general population of the same age and sex. However, we confirm an excess in lung cancer and hematological malignancies with RA.

Certain types of cancer are more frequent in some geographic areas, and survival differs from country to country (17, 18, 19, 20). This may be due to a different distribution of known and unknown risk

Acknowledgments

The authors express their acknowledgment of the outstanding logistics directed by Raquel Ruiz and by the thoughtfully supervising and data entry of Jesús Maese.

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    The EMECAR study was funded by the Spanish Society of Rheumatology, by the Spanish Foundation of Rheumatology, and by an independent research grant from Aventis, formerly from Hoechst Marion Roussel.

    1

    Components of the group are listed in the Appendix.

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