Abatacept treatment for rheumatoid arthritis

Abstract

Significant advances in our understanding of RA and its management have been made in the past decade, resulting in earlier intervention with biologic DMARDs, particularly in patients with evidence of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX naïve, and in patients with established RA and an inadequate response to MTX or TNF antagonists. Data from relevant clinical trials are overviewed, discussing the clinical efficacy of abatacept in early disease, the clinical outcomes over long-term treatment in different patient populations and the effects of abatacept on structural damage. Findings from integrated safety analyses of abatacept clinical trial data, representing 10,366 patient-years of exposure are described, and clinically important safety events, including serious infections, malignancies and autoimmune events, are highlighted. It is concluded that abatacept represents an effective treatment option with an established safety profile across different patient populations, including patients with both early and erosive RA and those with established disease. Furthermore, efficacy data from studies in patients with early disease suggest that the risk-benefit profile of abatacept may be more favourable when introduced earlier in the treatment paradigm.

Fig. 1

Radiographic progression in early and established RA over 1 year of abatacept treatment. (A) Mean change from baseline in TS, ES and JSN at Year 1 of the AGREE trial for abatacept plus MTX- and MTX alone-treated patients [23]. Adapted from Westhovens et al. [23] copyright 2009, with permission from the BMJ Publishing Group Ltd. (B) Mean change from baseline in TS, ES and JSN at Year 1 of the AIM trial for abatacept- and placebo-treated patients [42]. ABA: abatacept; PBO: placebo. Adapted from Kremer et al. [42].

Fig. 2

Long-term clinical efficacy over 5 years of treatment with abatacept. The proportion of patients originally randomized to the 10 mg/kg abatacept group of the Phase IIb trial experiencing LDAS (DAS-28 CRP ≤3.2) and DAS-28-defined remission (DAS-28 CRP < 2.6) by visit day. Responses are based on the intent-to-treat population for patients with data available at the visit of interest (as-observed analysis). Broken line represents the DB period; data are presented with 95% CIs. Reproduced from Westhovens et al. [25] with permission from the Journal of Rheumatology.

Fig. 3

Clinical efficacy over 1 year in the ATTEST trial. ACR responses achieved over Year 1 of the ATTEST trial. Data are presented for the intent-to-treat population with a last observation carried forward analysis. ^aInfliximab was administered on Days 1, 15, 43, 85 and then every 56 days thereafter; abatacept dosing occurred at each visit day. Reproduced from Schiff et al. [46] copyright 2008, with permission from the BMJ Publishing Group Ltd.