Rheumatoid Arthritis Treatment Evolution
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Rheumatoid Arthritis Treatment Evolution

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Questions and Answers

What is the dose range of specific FcRn inhibitors compared to IVIG?

  • 1-3 g/kg vs. 15-60 mg/kg
  • 15-60 mg/kg vs. 1-3 g/kg (correct)
  • 3-5 g/kg vs. 10-20 mg/kg
  • 5-10 g/kg vs. 2-4 g/kg

    • When was the first example of a specific FcRn inhibitor published in the literature?

  • 2005 (correct)
  • 2010
  • 2000
  • 2015

    • What was the maximal reduction in circulating IgG concentrations observed in the first-in-human study of Efgartigimod?

  • 75-85% (correct)
  • 50-60%
  • 60-70%
  • 90-95%

    • What was one of the significant findings regarding the risk of infections during the trial of Efgartigimod?

    <p>No increased risk in infections</p> Signup and view all the answers

    Which antibody is primarily affected by specific FcRn inhibitors, according to the content?

    <p>IgG</p> Signup and view all the answers

    What are disease modifying anti-rheumatic drugs primarily used for?

    <p>To slow disease progression</p> Signup and view all the answers

    Which of the following is NOT classified as a disease modifying agent?

    <p>Ibuprofen</p> Signup and view all the answers

    What role do pro-inflammatory cytokines play in autoimmune diseases?

    <p>They contribute to the pathogenesis and progression of disease</p> Signup and view all the answers

    Which statement about rheumatoid arthritis is true?

    <p>It leads to joint destruction</p> Signup and view all the answers

    Which type of agent is Tofacitinib classified under?

    <p>Synthetic agent</p> Signup and view all the answers

    What is a primary mechanism of TNF blockers in treating rheumatoid arthritis?

    <p>Inhibiting pro-inflammatory TNF signaling</p> Signup and view all the answers

    Which of the following is an example of a biological disease modifying agent?

    <p>Etanercept</p> Signup and view all the answers

    What is the primary purpose of improving diagnostic tools alongside treatment strategies in rheumatoid arthritis?

    <p>To enable earlier and more accurate treatment interventions</p> Signup and view all the answers

    What is the primary function of CAAR-T cells?

    <p>To attack and clear autoreactive B cells</p> Signup and view all the answers

    What replaces the scFv typically used in CAR-T therapy within CAAR-T cells?

    <p>An autoantigen</p> Signup and view all the answers

    How do CAAR-T cells achieve activation?

    <p>Through recognition of antigens by autoantibodies</p> Signup and view all the answers

    What is one potential advantage of CAAR-T therapy compared to other therapies?

    <p>It is more specific in targeting</p> Signup and view all the answers

    What is still uncertain about CAAR-T therapy?

    <p>Whether it can be a curative treatment</p> Signup and view all the answers

    What is one primary use of intravenous immunoglobulin (IVIG)?

    <p>Replacement in primary immunodeficiencies</p> Signup and view all the answers

    What is a possible mechanism by which IVIG works in autoimmune conditions?

    <p>Direct neutralization of autoantibodies</p> Signup and view all the answers

    What is the typical dosage range for IVIG when used to treat autoimmune conditions?

    <p>1-3 g/kg</p> Signup and view all the answers

    What is a significant financial drawback of using IVIG?

    <p>Costs are around $10,000 per dose</p> Signup and view all the answers

    How does IVIG alter the function of effector mechanisms in the immune response?

    <p>Biases towards anti-inflammatory responses</p> Signup and view all the answers

    What role do regulatory T cells (Treg) play in the immune response?

    <p>They promote anti-inflammatory responses.</p> Signup and view all the answers

    Which component of CAR-Treg therapy is essential for recognizing specific autoantigens?

    <p>The CAR component.</p> Signup and view all the answers

    How can CAR-Treg cells be generated?

    <p>By selectively transducing isolated Treg.</p> Signup and view all the answers

    What is a mechanism by which intravenous immunoglobulin (IVIG) works in autoimmune disorders?

    <p>Saturation of FcRn.</p> Signup and view all the answers

    Which of the following is NOT included in the mechanisms for disease-modifying treatments for autoimmune disorders?

    <p>Direct enhancement of autoantigen production.</p> Signup and view all the answers

    Study Notes

    Rheumatoid Arthritis Treatment Evolution

    • Treatment shifted from broadly acting drugs like NSAIDs and steroids to specific inhibitors, targeting specific disease mechanisms.

    Disease Modifying Agents (DMARDs)

    • DMARDs aim to slow disease progression.
    • Classified into synthetic (sDMARDs) and biological (bDMARDs).
    • sDMARDs include conventional agents like methotrexate and targeted agents like tofacitinib.
    • bDMARDs include original agents like anti-TNF mAbs, anti-CD20 mAbs, and biosimilars which are generic versions of original bDMARDs.

    Cytokines in Autoimmunity

    • Pro-inflammatory cytokines contribute to the development and progression of autoimmune diseases.
    • Numerous cytokine-blocking monoclonal antibodies (mAbs) have been approved to treat autoimmune conditions.

    Rheumatoid Arthritis

    • An autoimmune condition that leads to joint destruction.
    • Affects over 20 million people globally.
    • Women are 2.5 times more likely to be affected than men.
    • Treated with a variety of agents.

    TNF Blockers in Rheumatoid Arthritis

    • Etanercept, infliximab, and adalimumab are TNF blockers used to treat rheumatoid arthritis.
    • These drugs directly inhibit pro-inflammatory TNF signaling via the TNF receptor.

    Intravenous Immunoglobulin (IVIG)

    • Immunoglobulin replacement therapy used in primary immunodeficiencies to reconstitute the antibody pool.
    • Also used in autoimmune conditions at high doses (1-3 g/kg) to treat the condition.
    • IVIG is a plasma-derived product with high costs (~$10,000/dose).

    How IVIG Works in Autoimmunity

    • IVIG has multiple mechanisms of action in autoimmune conditions.
    • It may directly neutralize autoantibodies and cytokines.
    • It can alter the function of effector mechanisms, biasing them towards anti-inflammatory responses.
    • It can accelerate the elimination of pathogenic antibodies.

    FcRn Inhibitors

    • FcRn inhibitors impact tracer antibody pharmacokinetics at much lower doses than IVIG (15-60 mg/kg vs. 1-3 g/kg).
    • Specific FcRn inhibitor data was published in 2005, marking the first example of this type of therapy.

    Efgatigimod (Vyvgart) - First FcRn Inhibitor

    • First-in-human study showed sustained reduction in circulating IgG concentrations in healthy individuals.
    • Maximal effect was approximately 75-85% reduction in IgG levels.
    • No increased risk of infections was observed in the trial.

    Chimeric Autoantibody Receptor T-Cells (CAAR-T)

    • Analogous to CAR-T therapy used in cancer treatment.
    • T cells are engineered to attack and clear autoreactive B cells.
    • Activated by autoantibodies and B cell receptors recognizing a specific antigen, providing more specificity compared to other therapies.
    • Potential for curative effects, but further research is needed.

    Chimeric Antigen Receptor Regulatory T Cell (CAR-Treg)

    • CAR-Treg cells are tolerogenic T cells that promote anti-inflammatory responses.
    • Created by selectively transducing isolated Treg or by including FoxP3 in the CAR gene construct.
    • The 'CAR' component recognizes the specific autoantigen of interest.
    • Allows induction or restoration of tolerance to the specific antigen.

    Clinical Trials of Cell Therapies for Autoimmunity

    • Active clinical trials are exploring the use of CAR-T and CAAR-T therapies for autoimmune conditions.

    Summary

    • Disease modifying treatments for autoimmune disorders often modulate cytokine signaling and/or cell functions, employing kinase inhibitors, cytokine inhibitor mAbs, and B cell depleting mAbs.
    • IVIG efficacy in autoimmune disorders is attributed to the saturation of FcRn, leading to the development of FcRn inhibitors as a therapeutic class.
    • Next generation agents for autoimmune disorders may include cell therapies such as CAR-T and CAAR-T.

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    Description

    Explore the evolution of rheumatoid arthritis treatment, focusing on disease-modifying agents (DMARDs) and their classifications. Delve into the role of cytokines in autoimmunity and the advancements in targeted therapies. This quiz is essential for understanding modern approaches in managing rheumatoid arthritis.

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