Abatacept

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 18.12.2020

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Definition
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Selective co-stimulation modulator of CD80 and CD86. A recombinant, soluble fusion protein consisting of an extracellular domain of human cytotoxic T lymphocyte antigen 4 (CTLA-4) and a fragment of the Fc portion of human immunoglobulin IgG1.

Pharmacodynamics (Effect)
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To ensure that the immune response to an antigen is not exaggerated, the activation of T lymphocytes is regulated by a complex interaction of synergistically acting and inhibitory cytokines. Two signals emanating from antigen-presenting cells (APCs) are required for full T cell activation. The first signal consists of the interaction of the bound antigen with a T cell receptor. The second (costimulatory) signal consists of, for example, the binding of CD80 and CD86 molecules on the APC to the CD28 receptor on T cells. Without this interaction, the lymphocyte remains anergic. Shortly thereafter, activated T cells secrete a negative costimulation molecule, CTLA-4, which is homologous to CD28 but binds with higher affinity to CD80/86, thereby reducing further stimulation and an exuberant immune response by the activated T cell itself.

Abatacept binds like CTLA-4 to CD80 as well as CD86 and thus selectively modulates the second signal. It has a stronger effect on naive T-cells than on memory cells. According to studies, the levels of inflammatory markers and interleukin-2 (IL-2) receptor as a marker for T-cell activation decreased in a dose-dependent manner.

Indication
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  • Moderate to severe rheumatoid arthritis in combination with methotrexate to improve physical function and reduce the progression of joint involvement if the response to disease-modifying drugs, including at least one TNF inhibitor, is inadequate or if they are not tolerated due to undesirable side effects.
  • Manufacturer studies to evaluate the efficacy in psoriasis arthropathica and psoriasis vulgaris are still ongoing.

Limited indication
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Severe and uncontrolled infections such as sepsis and opportunistic infections

Dosage and method of use
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  • < 60 kg KG: 500 mg i.v. as a 30-minute i.v. infusion.
  • 60-100 kg KG: 750 mg i.v. as a 30-minute i.v. infusion.
  • > 100 kg KG 1 g i.v. as 30-minute i.v. infusion.

Undesirable effects
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  • Especially headaches and nausea. Weakening of the immune system against infections. According to the results of the study, severe infections are more frequent, especially in the urinary and respiratory tract and in the gastrointestinal tract (in 2.9 versus 1.7 percent of patients). Whether malignancies occur more frequently still has to be determined on the basis of progression observations based on long-term results.
  • The combination with a biological agent, especially TNF alpha blockers, e.g. Etanercept, Adalimumab, Infliximab, is particularly unfavourable with regard to susceptibility to effects and is therefore not recommended.

Preparations
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Orencia®

Literature
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  1. Kuek A, Hazleman BL, Ostör AJ (2007) Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgraduate Med J 83:251-260
  2. Furst DE, Breedveld FC et al (2006) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006 Ann Rheum Dis 65(Suppl 3): iii2-15

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Rheumatoid arthritis (ra);

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Last updated on: 18.12.2020