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abatacept + non-biologic disease modifying anti-rheumatic drug + anti-tumor necrosing factor therapy

Development stage
Discontinued
Lead developer
Bristol Myers Squibb
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Subcutaneous, Oral
01

Overview

This combination therapy consists of **abatacept**, a biologic agent that modulates T-cell co-stimulation, combined with a **non-biologic disease modifying anti-rheumatic drug (DMARD)** (such as methotrexate), and an **anti-tumor necrosis factor (anti-TNF) agent** (such as infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab)[1][2][3][5]. Abatacept inhibits T-cell activation by binding CD80/86, thereby blocking interactions with CD28, which is critical for T-cell co-stimulation[1]. Non-biologic DMARDs (commonly methotrexate) act via various mechanisms including anti-metabolite effects, suppression of immune function, and inhibition of inflammatory cell proliferation[3]. Anti-TNF agents block the activity of tumor necrosis factor alpha, a key inflammatory cytokine in rheumatoid arthritis[2][3][5]. The combination aims at providing broad immunomodulation but is associated with increased risk for serious adverse events (SAEs), especially infections[1]. Limited efficacy and safety concerns have led to recommendations against its use in rheumatoid arthritis[1].

02

Targets

CD80 (T-lymphocyte activation antigen CD80)DHFR (Dihydrofolate reductase)CD86 (T-lymphocyte activation antigen CD86)TNFA (Tumor necrosis factor alpha (soluble))

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