RESEARCH - 1673 autoimmune adverse events in the Orencia RA clinical development program: safety analysis with > 10,000 person-years of exposure

[Guest guest]

ACR 2008 Scientific Meeting

1673 Autoimmune Adverse Events in the Abatacept RA Clinical

Development Program: A Safety Analysis with > 10,000 Person-years of

Exposure

Background/Purpose: Use of anti-TNF agents has been associated with an

increased incidence of certain autoimmune diseases.1 Abatacept is the

first in a class of agents for the treatment of RA that selectively

modulates the CD80/CD86:CD28 co-stimulatory signal required for T-cell

activation.2 While no increases in anti-DNA or ANA antibodies have

been observed with abatacept use, it is important to assess the

occurrence of autoimmune diseases in the abatacept RA clinical

development program; this analysis is presented here.

Methods: Autoimmune AEs were examined in both the double-blind (DB)

and cumulative (DB and open-label periods) abatacept clinical trial

experience. A set of pre-specified MedDRA codes representing symptoms

or diseases that could be related to autoimmunity were used to

facilitate this analysis. Incidence rates (IRs) of autoimmune AEs were

computed for patients receiving abatacept in the DB period and the

cumulative experience. In addition, the overall IR was calculated in

annual intervals.

Results: During the DB period, among 1955 abatacept- and 989

placebo-treated patients, autoimmune AEs were reported in 28 (1.4%)

abatacept- and 8 (0.8%) placebo-treated patients. The majority of

autoimmune events reported by abatacept- and placebo-treated patients

were of mild or moderate intensity. The most common event was

psoriasis (abatacept: 0.5%; placebo: 0.0%). The cumulative abatacept

experience included a total of 4150 abatacept-treated RA patients from

8 clinical trials representing 10,365 person-years (p-y) of exposure

through December 2007. The median exposure to abatacept was 26.2

months. The cumulative IR of autoimmune AEs was 1.59/100 p-y; the

annual IRs are shown in Figure 1. The IRs of selected autoimmune AEs

are presented in Table 1.

Conclusions: In general, no increase in the incidence of autoimmune

diseases, including lupus and MS, was seen with abatacept exposure

over time; the IR of psoriasis has not changed with increased

exposure. The safety of abatacept with respect to individual

autoimmune events will continue to be monitored as part of a

post-marketing surveillance program and in abatacept patient

registries.

http://acr.confex.com/acr/2008/webprogram/Paper2684.html

Not an MD