Subcutaneous versus Intravenous Abatacept in Rheumatoid Arthritis

Chicago—The efficacy and safety of subcutaneous (SC) abatacept to treat rheumatoid arthritis (RA) was maintained over 24 months, according to investigators of a recent open-label long-term extension study that looked at 24-month follow-up from the ACQUIRE (Abatacept Comparison of Subcutaneous versus Intravenous in Inadequate Responders to Methotrexate) trial. Prior evidence from the ACQUIRE study showed comparable efficacy and safety of SC delivery of abatacept versus intravenous (IV) delivery at 6 months. The updated results were presented at the ACR meeting in a poster titled Subcutaneous (SC) Abatacept (ABA) versus Intravenous (IV) ABA in Patients (pts) with Rheumatoid Arthritis: Long-Term Data from the ACQUIRE (Abatacept Comparison of Subcutaneous versus Intravenous in Inadequate Responders to Methotrexate) Trial. The ACQUIRE trial was a multinational, phase 3b, double-blind study of patients with active RA and refractory to methotrexate who were randomized to receive SC abatacept (125 mg on days 1 and 8 and weekly thereafter) or IV abatacept (approximately 10 mg/kg based on weight range on days 1, 15, and 29 and every 4 weeks thereafter) for 6 months. The long-term extension study included patients who completed 6 months of treatment during the ACQUIRE trial. Inclusion criteria were patients >18 years of age with active RA, written consent, inadequate response to >3 months of methotrexate therapy with a stable dose of >15 mg/week for 28 days prior to randomization, and >10 swollen or >12 tender joint count and C-reactive protein >0.8 mg/dL. Of the 1385 patients in the ACQUIRE trial, 1372 (99.1%) patients completed the 6-month trial and entered the long-term extension. Of these, 1222 (89.1%) remained on therapy at the time the study was presented at the ACR meeting by lead author Mark C. Genovese, MD, clinical chief in the immunology clinic at Stanford University in Palo Alto, California. Results from the 18-month long-term extension showed that long-term administration of SC abatacept led to maintained improvement in signs and symptoms of RA, disease activity, and physical function, as well as a similar safety profile as demonstrated at 6 months. The study found that ACR criteria responses at 6 months were maintained at 24 months and were comparable between the SC and IV groups. The authors examined ACR 20, which was defined as a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in 3 of the following: (1) physician global assessment of disease; (2) patient global assessment of disease; (3) patient assessment of pain; (4) C-reactive protein or erythrocyte sedimentation rate; and (5) degree of disability in Health Assessment Questionnaire score. They also determined ACR 50 and ACR 70. At month 6, ACR 20, 50, and 70 for SC abatacept were 80.2%, 53.4%, and 27.7% and at 24 months were 74.4%, 49.4%, and 28.7%. For IV abatacept, the ACR 20, 50, and 70 response rates were 80.0%, 52.8%, and 26.7% at 6 months and 72.4%, 49.4%, and 26.9% at 24 months. The study also found that the rates of remission, as defined by the Disease Activity Score 28 (DAS28, based on C-reactive protein), were also maintained from 6 to 24 months between the SC and IV groups. At months 6 and 24, the rates of remission were 24.2% and 31.8% for SC abatacept and 25.0% and 30.6% for IV abatacept. In addition, physical function was maintained over time as shown by the proportion of patients who achieved a Health Assessment Questionnaire Disease Index (HAQ-DI) response (improvement from baseline >0.3) at 6 and 24 months. At 6 and 24 months, the proportion of patients achieving an HAQ-DI response was 72.6% and 63.2% for SC abatacept and 68.3% and 55.8% for IV abatacept. Overall, the safety profile of SC abatacept remained similar to that found at 6 months. The incidence of serious adverse events was 9.00 per 100 patient-years at 24 months and 9.02 at 6 months. The study found no increase in the incidence of infections or serious infections from 6 to 24 months, with rate of infections of 84.62% versus 47.64%, respectively, and the rate of serious infections of 1.48 and 1.97, respectively. The study also found a low incidence of immunogenicity, with low and transient anti-abatacept antibody titers maintained at 24 months. These results confirmed that SC abatacept offers comparable efficacy and safety to IV abatacept over the long-term, as well as emphasized that SC abatacept is a viable alternative route of self-administration that provides greater flexibility and convenience over IV administration for patients with RA.