Abatacept Approval for Rheumatoid Arthritis by European Commission
Recently, the European Commission has approved Abatacept intravenous (IV) infusion and subcutaneous (SC) injection, in combination with methotrexate (MTX), for treating rheumatoid arthritis (RA) not previously treated with MTX. It is the first biologic therapy with an indication in the European Union (EU) specifically relevant to the treatment of MTX-naive RA patients with highly active and progressive disease.
The clinical trial evidence supporting the recommendation was based on the studies of Abatacept comprising adult patients with high disease activity (mean DAS28-CRP of 5.4) accompanied by poor prognostic factors for rapidly progressive disease (positive for anti-CCP antibodies (also known as ACPA), and/or RF+, presence of baseline joint erosions). This approval will permit the expanded marketing of Abatacept in all 28 Member States of the EU.
This approval was established on data from two Phase 3 studies: In a 12 month, multinational, double-blind, randomized study of MTX-naive patients with early, rapidly progressing RA, Abatacept IV + MTX revealed outstanding efficacy vs MTX alone for those with moderate to severe RA. The study, AGREE, met its co-primary endpoints as defined by the proportion of patients achieving DAS28-CRP < 2.6 at 1 year (41% vs 23%, P<0.001) and inhibition of radiographic progression at 1 year (mean change in total Sharp score: 0.6 vs 1.1, P=0.04). The most commonly reported adverse events occurring at a rate of ≥ 10% in patients taking Abatacept in the adult RA clinical studies were headache, upper respiratory tract infection, nasopharyngitis, and nausea.
AVERT (Assessing Very Early Rheumatoid Arthritis Treatment) study provided the second Phase 3 data, which compared Abatacept 125 mg subcutaneous + MTX combination therapy, Abatacept 125 mg subcutaneous monotherapy, and MTX monotherapy in induction of DAS28-defined remission following 12 months of treatment in 351 adult patients with moderate to severe active, early RA (mean DAS28-CRP of 5.4; mean symptom duration less than 6.7 months) who did not had prior MTX or other DMARDs earlier (MTX-naive) treatment. Low prognostic factors for rapidly progressive disease was seen in patients. The co-primary results compared the proportion of patients with DAS28-portrayed remission (DAS28 CRP <2.6) at month 12 and both months 12 and 18 for Abatacept + MTX versus MTX alone. Identical results at 12 months were seen with other measures of efficacy encompassing Boolean remission (37.0%, Abatacept + MTX; 22.4%, MTX alone), CDAI remission (42%, Abatacept + MTX; 27.6% MTX alone), and SDAI remission (42%, Abatacept + MTX; 25% MTX alone).
Limitations of Use: Abatacept should not be administered concomitantly with TNF antagonists, and is not advised to use concomitantly with other biologic RA therapy, example anakinra.
Note concerning SC ORENCIA: The safety and efficacy of SC Abatacept have not been depicted in patients under 18 years of age.