MONT TREMBLANT, QUE. — Cumulative postmarketing surveillance data have shown the rates of lymphoma and lung cancer among rheumatoid arthritis patients treated with abatacept are not higher than those among patients treated with conventional disease-modifying drugs.
Researchers compared cancer rates among more than 4,000 patients treated with abatacept (Orencia) with those in a reference population of about 94,000 rheumatoid arthritis (RA) patients treated with nonbiologic disease-modifying antirheumatic drugs (DMARDs), and with rates in the general population, Dr. Diane Lacaille reported at the annual meeting of the Canadian Rheumatology Association.
Published literature suggests the overall incidence of certain malignancies like lymphoma and lung cancer is increased in RA patients. The initial double-blind studies of abatacept also suggest an increase in malignancies, particularly lung cancer, among patients receiving the active treatment. Bristol-Myers Squibb Co., maker of abatacept, sponsored the postmarketing surveillance study. The analysis included safety data from two phase II RA trials and five phase III studies, as well as the cumulative abatacept experience of a total of 4,134 patients representing approximately 8,400 person-years of exposure, according to Dr. Lacaille of the University of British Columbia, Vancouver.
Six cohorts containing approximately 94,000 DMARD-treated patients from across the world were used as a reference population, she said during a poster presentation. Dr. Lacaille and her colleagues derived rates of malignancy in the U.S. general population from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.
The observed incidence of overall malignancies (excluding nonmelanoma skin cancer) per 100 patient-years was 0.59 in the double-blind trials and 0.61 in the ongoing cumulative abatacept experience. The corresponding standardized incidence ratio (SIR) among DMARD-treated patients, calculated by dividing the number of observed cancers by the number of expected cancers adjusted for age, gender, and duration of exposure, was 0.68. In the U.S. general population, the corresponding SIR was 0.8.
For lung cancer, the observed incidence was 0.24 in the abatacept trials and 0.15 in the abatacept surveillance data; the SIRs were 1.07 in the DMARD-treated patients and 1.5 in the general population.
The lymphoma rates were identical, 0.06, in the trials and the cumulative experience with abatacept; the corresponding SIRs were 0.89 in the DMARD cohorts and 2.2 in the general population. For the RA cohorts, the confidence intervals for the incidence rates and SIRs overlap.
Finally, the breast cancer rates were 0.06 in the trials and 0.08 in the surveillance data, with corresponding SIRs of 0.42 for the DMARD cohorts and 0.4 for the general population
With this longer exposure than in the double-blind studies, the observed incidence rates for malignancies remain unchanged, said Dr. Lacaille. Moreover, overall and individual malignancy SIRs are consistent with what would be expected in an RA population and, when compared with the U.S. general population, are consistent with the literature, she added.
“I think it's reassuring to see that the SIRs are certainly not increased for cancer overall or for lymphoma or particularly for lung cancer among abatacept-treated patients, when compared with the DMARD cohorts,” she said.
The overall safety of abatacept will continue to be monitored in this surveillance program.