Infections requiring hospitalization in the abatacept clinical development program: an epidemiological assessment
1 Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Route 206 and Province Line Roads, Lawrenceville, NJ 08540, USA
2 Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital Solna, Rheumatology Unit d2:01, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden
3 Division of Rheumatology, Department of Medicine, Arthritis Research Centre of Canada, University of British Columbia, 895 West 10th Ave., Vancouver, BC V5Z 1L7, Canada
4 Arc Epidemiology Unit, School of Medicine, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
5 Current address: Medical School, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK
6 Department of Internal Medicine, National Data Bank for Rheumatic Diseases, Arthritis Research Foundation and University of Kansas, 1035 N. Emporia, Suite 288, Wichita, KS 67214, USA
7 Global Biostatistics, 311 Pennington Rocky Hill Road, Bristol-Myers Squibb, Hopewell, NJ 08525, USA
8 Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, 3755 Cote Ste-Catherine, Montreal, Québec H3T 1E2, Canada
9 Departments of Medicine and Epidemiology and Preventive Medicine, University of Maryland School of Medicine, 10 S. Pine St., MSTF 8-34, Baltimore, MD 21201, USA
Arthritis Research & Therapy 2010, 12:R67 doi:10.1186/ar2984Published: 14 April 2010
Patients with rheumatoid arthritis (RA) have an increased risk of infection and this risk appears to be higher with anti-TNF (tumor necrosis factor) agents. We pooled data from the cumulative abatacept RA clinical development program, both double-blind and open-label periods, to estimate the incidence rates (IRs) of infections requiring hospitalization including pneumonia and opportunistic infections, in comparison with RA patients treated with non-biologic disease-modifying antirheumatic drugs (DMARDs) from several reference cohorts.
Infections reported in seven abatacept clinical trials of RA patients (double-blind and open-label periods) were tabulated. Comparisons were made between the observed IRs in abatacept-treated patients and those in over 133,000 patients exposed to non-biologic DMARDs in six reference RA cohorts. Age- and sex-adjusted IRs of infections requiring hospitalization, including pneumonia (most frequent hospital infection), were used to estimate the expected IRs with abatacept by the method of indirect adjustment. Standardized incidence ratios (SIR) and 95% CI were calculated comparing incidence in the cumulative abatacept experience with incidence in each RA cohort.
A total of 1,955 (double-blind period) and 4,134 (double-blind + open-label periods with a cumulative exposure of 8,392 person-years) abatacept-treated RA patients were analyzed. Observed IRs for infections requiring hospitalization during the double-blind period were 3.05 per 100-patient years for abatacept-treated patients and 2.15 per 100 patient years for placebo. In the cumulative population, observed IR for infections requiring hospitalization was 2.72 per 100-patient years. Rates for abatacept were similar to expected IRs based on other RA non-biologic DMARD cohorts.
IRs of infections requiring hospitalization and pneumonia in abatacept trials are consistent with expected IRs based on reference RA DMARD cohorts. RA patients are at higher risk of infection compared with the general population, making the RA DMARD cohorts an appropriate reference group. The safety of abatacept, including incidence of infections requiring hospitalization, will continue to be monitored in a post-marketing surveillance program.