Coupled with the fact that there were no new safety concerns identified, these findings further solidify the safety and effectiveness of abatacept for RA patients.
Abatacept-treated patients experiencing rheumatoid arthritis (RA) symptoms had relatively low rates of opportunistic infections (OIs) when compared with placebo-treated counterparts, according to an analysis of 16 randomized, double-blind, open-label clinical trials.1 OIs were further analyzed separately in both controlled and cumulative periods and were consistent with previously reported findings on the subject. Although the study was limited by short durations of exposure, investigators evaluated their findings by using all available data from the RA abatacept development program.
The study followed 7044 patients receiving abatacept, a selective T cell co-stimulation modulator with a history of being an effective and well-tolerated treatment for RA, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months. Incidence rates (IRs) (95% confidence intervals) of OIs were 0.17 (0.05–0.43) for abatacept and 0.56 (0.22–1.15) for the placebo during the controlled periods and 0.21 (0.15–0.28) for abatacept during the cumulative periods.
During the controlled periods, 2653 patients received abatacept and 1485 received the placebo; in the cumulative periods, 7044 patients received abatacept. Demographic, disease characteristics, and concomitant medications were similar across both groups. The mean age was 51.5 years (standard deviation [SD] 12.6) for the controlled period and 51.7 years (12.4) for the cumulative period; 80.6% and 79.1% of patients were female, respectively. The mean duration of exposure to abatacept in the controlled and cumulative periods was 10.8 (3.3) and 36.9 (26.2) months, respectively.
Common OIs reported during this time were tuberculosis (TB) and herpes. There was 1 case of TB in both the abatacept and placebo groups during the controlled periods and 13 verified TB cases reported in the cumulative period. Additionally, herpes zoster was reported more often with abatacept versus placebo in the controlled periods. Still, it should be noted that “the IR for TB observed in the cumulative data was low and similar to the IRs observed with abatacept versus placebo in the controlled periods of the clinical trials. The risk of TB in patients with RA has been shown to be elevated due to both the disease and the mechanism of action of many RA therapies, including steroids. However, risk of TB is largely driven by the country where such studies are conducted (ie, endemic areas versus non-endemic areas).” This data may be skewed by instances such as reactivation of latent TB, false negative results, and newly acquired TB cases in endemic countries. For the herpes outcomes, the data from both periods line up with the previously reported range, which indicates abatacept as a safe choice for RA patients.
Investigators evaluated the 222 potential OI cases that occurred during the study. They found that none of the patients in the controlled period had more than 1 OI event, and only 3 patients in the cumulative period experienced recurrent OIs. “Overall, the types of OIs reported in patients receiving abatacept were not unexpected,” the research team concluded. “The rates of OIs between the abatacept and placebo groups were low and similar in the controlled periods. IRs of OIs over time remained stable with long-term abatacept use when considering open-label extension data. In the cumulative periods, the IR of OIs seen with abatacept was low and consistent with that observed in the controlled period.”
The study ran into predictable limitations, as OIs are historically inconsistently classified. Specifically, “a full list of all OIs included in the definition is often omitted from publications. Thus, it is difficult to compare published OI rates unless a list of included OIs is provided by the authors…In the published review, the definition of an OI was formulated as ‘the presence, or specific presentation, of a pathogen that suggests a higher likelihood of an alteration in host immunity.’ In the present analysis, the authors applied this definition of an OI to the cases reported in these studies as a form of adjudication, to enhance clinical relevance and to improve generalizability of the findings.”
However, despite the disputed definition of an OI, the analysis of the long-term clinical trial data concludes that patients with RA who are being treated with abatacept had similar rates of OIs, such as TB and herpes, when compared with patients receiving a placebo in the controlled periods of the trials. Additionally, the IRs of OIs were consistent in the cumulative periods for abatacept as well. Coupled with the fact that there were no new safety concerns identified during the trials, these findings further solidify the safety and effectiveness of abatacept for RA patients.
Simon TA, Dong L, Winthrop KL. Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data. Arthritis Res Ther. 2021;23(1):17. Published 2021 Jan 11. doi:10.1186/s13075-020-02399-2