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.

Applications of systems approaches in the study of rheumatic diseases

“…In particular, CD86 was identified as a strong modulator of DAS28, tender joints, or swollen joints, and represents an important TNF-α-independent mechanism active in RA patients. This finding is consistent with the therapeutic impact of modulating CD86 with abatacept (CTLA4-Ig) as an alternative to TNF-α inhibitors [ 47 ].…”

Applications of systems approaches in the study of rheumatic diseases

“…In particular, CD86 was identified as a strong modulator of DAS28, tender joints, or swollen joints, and represents an important TNF-α-independent mechanism active in RA patients. This finding is consistent with the therapeutic impact of modulating CD86 with abatacept (CTLA4-Ig) as an alternative to TNF-α inhibitors [ 47 ].…”

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry

“…A second hypothesis was to only consider the serious infections that occurred while patients were treated with ABA since there is no demonstration of a persistent immunological effect of ABA after its discontinuation. Whatever the way of defining the at-risk period, the rate of serious infections was slightly higher than that observed in controlled trials of intravenous ABA during the double-blind period (3.7/100 patient-years) or in their open-phase follow-up (2.9/100 patient-years)14 and than that in five controlled trials of subcutaneous ABA (1.9/100 patient-years) 15. In patients with RA treated with RTX in the AutoImmunity and Rituximab registry, a registry with the same methodology as ORA, the occurrence of serious infections was similar (5.0/100 patient-years) as in the present study,4 being aware that the patient characteristics might differ.…”

Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy

“…Aseptic meningoencephalitis,8 herpes simplex encephalitis9 and EBV encephalitis10 have been reported in patients receiving TNF-α antagonists. The incidence rate of serious infections or opportunistic infections with abatacept therapy tends to be lower than that with TNF-α antagonist therapy 4. The present case had been receiving methotrexate, prednisolone and TNF-α antagonist for 6 years.…”

Applications of systems approaches in the study of rheumatic diseases

“…In particular, CD86 was identified as a strong modulator of DAS28, tender joints, or swollen joints, and represents an important TNF-α-independent mechanism active in RA patients. This finding is consistent with the therapeutic impact of modulating CD86 with abatacept (CTLA4-Ig) as an alternative to TNF-α inhibitors [ 47 ].…”

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry

“…A second hypothesis was to only consider the serious infections that occurred while patients were treated with ABA since there is no demonstration of a persistent immunological effect of ABA after its discontinuation. Whatever the way of defining the at-risk period, the rate of serious infections was slightly higher than that observed in controlled trials of intravenous ABA during the double-blind period (3.7/100 patient-years) or in their open-phase follow-up (2.9/100 patient-years)14 and than that in five controlled trials of subcutaneous ABA (1.9/100 patient-years) 15. In patients with RA treated with RTX in the AutoImmunity and Rituximab registry, a registry with the same methodology as ORA, the occurrence of serious infections was similar (5.0/100 patient-years) as in the present study,4 being aware that the patient characteristics might differ.…”

Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy

“…Aseptic meningoencephalitis,8 herpes simplex encephalitis9 and EBV encephalitis10 have been reported in patients receiving TNF-α antagonists. The incidence rate of serious infections or opportunistic infections with abatacept therapy tends to be lower than that with TNF-α antagonist therapy 4. The present case had been receiving methotrexate, prednisolone and TNF-α antagonist for 6 years.…”

Applications of systems approaches in the study of rheumatic diseases

“…In particular, CD86 was identified as a strong modulator of DAS28, tender joints, or swollen joints, and represents an important TNF-α-independent mechanism active in RA patients. This finding is consistent with the therapeutic impact of modulating CD86 with abatacept (CTLA4-Ig) as an alternative to TNF-α inhibitors [ 47 ].…”

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry

“…A second hypothesis was to only consider the serious infections that occurred while patients were treated with ABA since there is no demonstration of a persistent immunological effect of ABA after its discontinuation. Whatever the way of defining the at-risk period, the rate of serious infections was slightly higher than that observed in controlled trials of intravenous ABA during the double-blind period (3.7/100 patient-years) or in their open-phase follow-up (2.9/100 patient-years)14 and than that in five controlled trials of subcutaneous ABA (1.9/100 patient-years) 15. In patients with RA treated with RTX in the AutoImmunity and Rituximab registry, a registry with the same methodology as ORA, the occurrence of serious infections was similar (5.0/100 patient-years) as in the present study,4 being aware that the patient characteristics might differ.…”

Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy

“…Aseptic meningoencephalitis,8 herpes simplex encephalitis9 and EBV encephalitis10 have been reported in patients receiving TNF-α antagonists. The incidence rate of serious infections or opportunistic infections with abatacept therapy tends to be lower than that with TNF-α antagonist therapy 4. The present case had been receiving methotrexate, prednisolone and TNF-α antagonist for 6 years.…”