Methotrexate at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with rheumatoid arthritis: a nationwide population-based cohort study.

BACKGROUND

We investigated whether taking methotrexate (MTX) is associated with a lower risk of new-onset cancers in patients with rheumatoid arthritis (RA).

METHODS

We conducted a 12-year retrospective cohort study from a population-based National Health Insurance Research Database in Taiwan. A total of 21,699 patients with newly diagnosed RA were enrolled during 2000-2009. The overall cancer rate was compared between 10,352 new users of MTX and 11,347 non-users. We used the WHO Defined Daily Dose (DDD) as a tool to assess drug exposure. Cox proportional hazard regression models were used to estimate the hazard ratio (HR) of disease after controlling for demographics and other comorbidities.

RESULTS

After adjusting for age, sex, cancer-related comorbidities, and RA-combined medication, the HR of cancer risk was 0.87 (95% CI = 0.74-1.02) for the MTX user group compared with the MTX non-user group. The cumulative incidence of cancer in the MTX non-user group was significantly higher than that of the MTX user group (log-rank test  < 0.001). In the low accumulative dose group [cumulative dose <1125 mg, cumulative defined daily dose (cDDD) <450], the HR of cancer risk for MTX users was 1.20 (95% CI = 1.01-1.42) compared with the MTX-non-user group. However, the adjusted HR of cancer risk was reduced to 0.66 (95% CI = 0.49-0.87) in MTX middle-dose users (cumulative dose 1125-2250 mg, cDDD: 450-899) and 0.33 (95% CI = 0.23-0.48) for the MTX high-dose group (cumulative dose ⩾2250 mg, cDDD ⩾900), respectively ( for trend < 0.0001).

CONCLUSION

MTX at middle and high accumulative doses might be associated with lower risk of new-onset cancers in patients with RA.