Safety of Abatacept Administered Intravenously in Treatment of Rheumatoid Arthritis: Integrated Analyses of up to 8 Years of Treatment from the Abatacept Clinical Trial Program

Abstract

Objective.To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA).Methods.Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population.Results.There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon.Conclusion.Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.

Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

“…Moreover, the longterm safety profile seen here with SC ABA is similar to the consistent longterm profile demonstrated for IV ABA, which was reported for 4419 patients with more than 12,000 cumulative patient-years of exposure 15 , and demonstrated that IR of hospitalized infections (3.35, 2.63, 2.31, 2.33, 1.55, 2.48, and 3.03 from years 1 to 7, respectively) and malignancies (0.62, 0.55, 0.81, 0.81, 0.99, 0.53, and 1.66 from years 1 to 7, respectively) evaluated at 12-month intervals remained relatively stable with increasing ABA exposure.…”

Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

“…The IR for deaths (0.75 events/100 PY) was stable over the study duration and is comparable with previously reported rates for SC ABA 9,12,14 . The IR for serious infections (1.68) was similar to that previously reported for longterm IV ABA (hospitalized infections, 1.55) 15 and SC ABA (1.79) 9 . Similar to previous reports, there was a low rate of opportunistic infections and new tuberculosis infections or reactivation 9 .…”

Biological Therapy and Infection in Rheumatoid Arthritis Patients: Modern Aspects

“…Продемонстриро-вано нарастание частоты СКИ при комбинации АБЦ с иФНО-α [22]. В целом при оценке 8 крупных РКИ частота развития СИ при внутривенном (в/в) введении АБЦ была выше, чем в контроле (5,5% и 2,0%, ОР 3,68 и 2,6 соот-ветственно) и снижалась при более длительном (>1 года) периоде наблюдения (ОР 2,87) [23]. В рамках реальной клинической практики (французский регистр ORA) часто-та развития СКИ при в/в введении АБЦ составила 7,1%, или 4,1 на 100 пациенто-лет.…”