Malignancies in an rheumatoid arthritis (RA) clinical development program: An epidemiological assessment

Objective: This study demonstrated the use of Surveillance, Epidemiology, and End Results (SEER) and published literature to evaluate the risk of malignancies in a RA trial population. Methods: Age- and sex-specific incidence rates (IR) of malignancies in a clinical trial program were calculated; equivalent IRs obtained from SEER were used to compute observed and expected numbers by the method of indirect adjustment. Numbers of malignancies observed in trials were compared to numbers expected based on the general population (GP) using standardized incidence ratios (SIRs). A literature search was conducted on Medline for population-based observational studies published from 1990 through Oct 2006 assessing the risk of cancer in RA patients. We graphically compared the SIRs from the RA trial patients to those presented in the literature. Results: Crude IR and SIRs using SEER data were computed for overall malignancies lymphoma, lung, breast and colo-rectal. A total of 17 publications examining SIRs of malignancy in RA patients met our inclusion criteria: 12 studies reported SIRs for lymphoma, 10 for lung, 7 for breast and 8 for colorectal. Trial SIRs fell within the range of SIRs presented in the literature. Conclusion: Despite limitations, SIRs of trial patients compared to GP were similar to those reported in the literature. The published literature suggests that RA patients are at higher risk of lung cancer and lymphoma and lower risk of colorectal cancer than the GP, making the GP a non-ideal reference population. The SIRs we obtained were also consistent with other RA cohorts.