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Questions and Answers
What is the dose range of specific FcRn inhibitors compared to IVIG?
What is the dose range of specific FcRn inhibitors compared to IVIG?
When was the first example of a specific FcRn inhibitor published in the literature?
When was the first example of a specific FcRn inhibitor published in the literature?
What was the maximal reduction in circulating IgG concentrations observed in the first-in-human study of Efgartigimod?
What was the maximal reduction in circulating IgG concentrations observed in the first-in-human study of Efgartigimod?
What was one of the significant findings regarding the risk of infections during the trial of Efgartigimod?
What was one of the significant findings regarding the risk of infections during the trial of Efgartigimod?
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Which antibody is primarily affected by specific FcRn inhibitors, according to the content?
Which antibody is primarily affected by specific FcRn inhibitors, according to the content?
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What are disease modifying anti-rheumatic drugs primarily used for?
What are disease modifying anti-rheumatic drugs primarily used for?
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Which of the following is NOT classified as a disease modifying agent?
Which of the following is NOT classified as a disease modifying agent?
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What role do pro-inflammatory cytokines play in autoimmune diseases?
What role do pro-inflammatory cytokines play in autoimmune diseases?
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Which statement about rheumatoid arthritis is true?
Which statement about rheumatoid arthritis is true?
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Which type of agent is Tofacitinib classified under?
Which type of agent is Tofacitinib classified under?
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What is a primary mechanism of TNF blockers in treating rheumatoid arthritis?
What is a primary mechanism of TNF blockers in treating rheumatoid arthritis?
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Which of the following is an example of a biological disease modifying agent?
Which of the following is an example of a biological disease modifying agent?
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What is the primary purpose of improving diagnostic tools alongside treatment strategies in rheumatoid arthritis?
What is the primary purpose of improving diagnostic tools alongside treatment strategies in rheumatoid arthritis?
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What is the primary function of CAAR-T cells?
What is the primary function of CAAR-T cells?
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What replaces the scFv typically used in CAR-T therapy within CAAR-T cells?
What replaces the scFv typically used in CAR-T therapy within CAAR-T cells?
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How do CAAR-T cells achieve activation?
How do CAAR-T cells achieve activation?
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What is one potential advantage of CAAR-T therapy compared to other therapies?
What is one potential advantage of CAAR-T therapy compared to other therapies?
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What is still uncertain about CAAR-T therapy?
What is still uncertain about CAAR-T therapy?
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What is one primary use of intravenous immunoglobulin (IVIG)?
What is one primary use of intravenous immunoglobulin (IVIG)?
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What is a possible mechanism by which IVIG works in autoimmune conditions?
What is a possible mechanism by which IVIG works in autoimmune conditions?
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What is the typical dosage range for IVIG when used to treat autoimmune conditions?
What is the typical dosage range for IVIG when used to treat autoimmune conditions?
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What is a significant financial drawback of using IVIG?
What is a significant financial drawback of using IVIG?
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How does IVIG alter the function of effector mechanisms in the immune response?
How does IVIG alter the function of effector mechanisms in the immune response?
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What role do regulatory T cells (Treg) play in the immune response?
What role do regulatory T cells (Treg) play in the immune response?
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Which component of CAR-Treg therapy is essential for recognizing specific autoantigens?
Which component of CAR-Treg therapy is essential for recognizing specific autoantigens?
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How can CAR-Treg cells be generated?
How can CAR-Treg cells be generated?
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What is a mechanism by which intravenous immunoglobulin (IVIG) works in autoimmune disorders?
What is a mechanism by which intravenous immunoglobulin (IVIG) works in autoimmune disorders?
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Which of the following is NOT included in the mechanisms for disease-modifying treatments for autoimmune disorders?
Which of the following is NOT included in the mechanisms for disease-modifying treatments for autoimmune disorders?
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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.
