Podcast
Questions and Answers
What is the primary focus regarding monosodium urate?
What is the primary focus regarding monosodium urate?
- Crystal types (correct)
- Maintenance
- Pathophysiology
- Aetiology
Which crystal type is associated with needle-shaped crystals and strong negative birefringence under polarizing light?
Which crystal type is associated with needle-shaped crystals and strong negative birefringence under polarizing light?
- Basic calcium phosphate
- Calcium pyrophosphate
- Monosodium urate (correct)
- Hydroxyapatite
In what condition are rhomboid crystals with weak positive birefringence typically observed?
In what condition are rhomboid crystals with weak positive birefringence typically observed?
- Subacute arthritis
- Milwaukee shoulder
- Gout
- Pseudogout (correct)
What percentage of gout patients typically exhibit elevated uric acid concentrations?
What percentage of gout patients typically exhibit elevated uric acid concentrations?
What physiological process is most directly associated with the formation of monosodium urate crystals?
What physiological process is most directly associated with the formation of monosodium urate crystals?
Which of the following dietary components contributes to uric acid production?
Which of the following dietary components contributes to uric acid production?
What percentage of uric acid is typically excreted through the kidneys?
What percentage of uric acid is typically excreted through the kidneys?
What is directly activated by the phagocytosis of MSU crystals?
What is directly activated by the phagocytosis of MSU crystals?
What is the role of aggregated NETs in gout pathophysiology?
What is the role of aggregated NETs in gout pathophysiology?
Which joint is most commonly affected at the onset of gout?
Which joint is most commonly affected at the onset of gout?
Which of the following should be ruled out when a patient presents with swelling and intense pain, potentially associated with fever?
Which of the following should be ruled out when a patient presents with swelling and intense pain, potentially associated with fever?
How long does a typical self-limited gout flare last?
How long does a typical self-limited gout flare last?
What is the primary action of NSAIDs in the treatment of gout flares?
What is the primary action of NSAIDs in the treatment of gout flares?
Which of the following is important to confirm before administering glucocorticoids intra-articularly?
Which of the following is important to confirm before administering glucocorticoids intra-articularly?
What is the typical length of a prednisolone course when used to treat gout flares?
What is the typical length of a prednisolone course when used to treat gout flares?
What is the primary mechanism of action of colchicine?
What is the primary mechanism of action of colchicine?
What is the most common adverse effect experienced by patients taking colchicine?
What is the most common adverse effect experienced by patients taking colchicine?
Concurrent use of colchicine with which substrate requires careful monitoring?
Concurrent use of colchicine with which substrate requires careful monitoring?
Which cytokine is targeted by Anakinra?
Which cytokine is targeted by Anakinra?
How is Anakinra administered?
How is Anakinra administered?
Which of the following non-pharmacological interventions is recommended for patients with gout?
Which of the following non-pharmacological interventions is recommended for patients with gout?
Which class of medications may increase uric acid levels?
Which class of medications may increase uric acid levels?
What is the primary mechanism of action of allopurinol?
What is the primary mechanism of action of allopurinol?
Why is prophylaxis with colchicine or NSAIDs recommended when initiating allopurinol?
Why is prophylaxis with colchicine or NSAIDs recommended when initiating allopurinol?
Which HLA allele is associated with severe cutaneous adverse reactions to allopurinol?
Which HLA allele is associated with severe cutaneous adverse reactions to allopurinol?
A patient is taking azathioprine for IBD. Which medication used for gout treatment is contraindicated and why?
A patient is taking azathioprine for IBD. Which medication used for gout treatment is contraindicated and why?
In what patient population is Febuxostat particularly useful?
In what patient population is Febuxostat particularly useful?
What is the effect of rapid lowering of uric acid concentration on gout flares?
What is the effect of rapid lowering of uric acid concentration on gout flares?
What is the primary mechanism of action of uricosuric agents like probenecid?
What is the primary mechanism of action of uricosuric agents like probenecid?
What is a potential adverse effect of uricosuric agents like probenecid?
What is a potential adverse effect of uricosuric agents like probenecid?
What is the mechanism of action of uricase?
What is the mechanism of action of uricase?
Which formulation of uricase is used for severe refractory gout?
Which formulation of uricase is used for severe refractory gout?
What is a key factor in the decision to use Non-steroidal anti-inflammatory drugs (NSAIDs) for treating gout flares?
What is a key factor in the decision to use Non-steroidal anti-inflammatory drugs (NSAIDs) for treating gout flares?
Why is it important to closely monitor the uric acid concentration when using Allopurinol?
Why is it important to closely monitor the uric acid concentration when using Allopurinol?
If a patient experiences adverse effects from Allopurinol, which is a suitable alternative for lowering uric acid?
If a patient experiences adverse effects from Allopurinol, which is a suitable alternative for lowering uric acid?
Describe how to lower the risk of acute flares when starting urate-lowering therapies.
Describe how to lower the risk of acute flares when starting urate-lowering therapies.
Why is Rasburicase more commonly used in tumour lysis syndrome rather than gout?
Why is Rasburicase more commonly used in tumour lysis syndrome rather than gout?
How does alcohol consumption affect uric acid levels in the body?
How does alcohol consumption affect uric acid levels in the body?
How should Aspirin be administered to gout patients to decrease uric acid level?
How should Aspirin be administered to gout patients to decrease uric acid level?
What is the primary target of Anti-IL1 medications in the treatment of crystal arthropathies?
What is the primary target of Anti-IL1 medications in the treatment of crystal arthropathies?
Which of the following is a key consideration when using glucocorticoids, either systemically or intra-articularly, for gout flares?
Which of the following is a key consideration when using glucocorticoids, either systemically or intra-articularly, for gout flares?
Which of the following best describes the mechanism through which rapid uric acid concentration reduction can precipitate a gout flare?
Which of the following best describes the mechanism through which rapid uric acid concentration reduction can precipitate a gout flare?
What is the MOST common adverse effect associated with colchicine?
What is the MOST common adverse effect associated with colchicine?
Besides Allopurinol, which of the following medications also inhibits Xanthine Oxidase to lower uric acid levels?
Besides Allopurinol, which of the following medications also inhibits Xanthine Oxidase to lower uric acid levels?
Why is it important to review a patient's current medication list when treating gout?
Why is it important to review a patient's current medication list when treating gout?
Which dietary modification is MOST likely to benefit a patient with gout?
Which dietary modification is MOST likely to benefit a patient with gout?
What is the primary mechanism of action of Probenecid in treating gout?
What is the primary mechanism of action of Probenecid in treating gout?
Which factor makes Rasburicase more suitable for use in tumor lysis syndrome than in the routine management of gout?
Which factor makes Rasburicase more suitable for use in tumor lysis syndrome than in the routine management of gout?
Besides a low purine diet, what other non-pharmacological intervention is beneficial for patients with gout?
Besides a low purine diet, what other non-pharmacological intervention is beneficial for patients with gout?
If a patient with gout also has a history of nephrolithiasis, which medication should be used with caution due to the risk of increasing calcium urinary excretion?
If a patient with gout also has a history of nephrolithiasis, which medication should be used with caution due to the risk of increasing calcium urinary excretion?
What is a key reason for using prophylaxis (e.g., with colchicine or NSAIDs) when initiating urate-lowering therapy such as allopurinol?
What is a key reason for using prophylaxis (e.g., with colchicine or NSAIDs) when initiating urate-lowering therapy such as allopurinol?
What is the primary reason febuxostat is used in patients with renal failure or those who cannot tolerate allopurinol?
What is the primary reason febuxostat is used in patients with renal failure or those who cannot tolerate allopurinol?
What is the mechanism by which low-dose aspirin can potentially worsen gout?
What is the mechanism by which low-dose aspirin can potentially worsen gout?
What is the MOST appropriate first-line treatment during an acute gout flare, provided there are no contraindications?
What is the MOST appropriate first-line treatment during an acute gout flare, provided there are no contraindications?
Which of the following most accurately describes tophi?
Which of the following most accurately describes tophi?
Which of the following factors contributes to the increased risk of gout flares when initiating urate-lowering therapy?
Which of the following factors contributes to the increased risk of gout flares when initiating urate-lowering therapy?
What is a contraindication for the use of intra-articular glucocorticoids?
What is a contraindication for the use of intra-articular glucocorticoids?
Why is it important to monitor for drug-drug interactions when prescribing colchicine?
Why is it important to monitor for drug-drug interactions when prescribing colchicine?
What is the most significant advantage of using Pegloticase over other urate-lowering therapies?
What is the most significant advantage of using Pegloticase over other urate-lowering therapies?
In a patient experiencing frequent gout flares despite being on allopurinol, what would be the next appropriate step in management?
In a patient experiencing frequent gout flares despite being on allopurinol, what would be the next appropriate step in management?
A patient with a history of cardiovascular disease is diagnosed with gout. Which treatment approach would be MOST appropriate?
A patient with a history of cardiovascular disease is diagnosed with gout. Which treatment approach would be MOST appropriate?
In treating gout with Allopurinol, the uric acid target is:
In treating gout with Allopurinol, the uric acid target is:
Which of the following is the appropriate length of prednisolone course for treating gout flares?
Which of the following is the appropriate length of prednisolone course for treating gout flares?
Which of the following is a potential strategy to improve the tolerability of oral colchicine?
Which of the following is a potential strategy to improve the tolerability of oral colchicine?
What is true about chronic gout?
What is true about chronic gout?
What percentage of uric acid is reabsorbed in proximal tubule?
What percentage of uric acid is reabsorbed in proximal tubule?
What crystal type is associated with calcium pyrophosphate?
What crystal type is associated with calcium pyrophosphate?
Which of the following best describes the effectiveness of managing acute gout flares with intra-articular glucocorticoids?
Which of the following best describes the effectiveness of managing acute gout flares with intra-articular glucocorticoids?
A patient is prescribed azathioprine for rheumatoid arthritis. Which gout treatment requires caution due to potential drug-drug interaction?
A patient is prescribed azathioprine for rheumatoid arthritis. Which gout treatment requires caution due to potential drug-drug interaction?
A patient is on macrolide antibiotics, what drug requires caution as it is reliant on P450 enzyme (most drugs metabolised through P450)?
A patient is on macrolide antibiotics, what drug requires caution as it is reliant on P450 enzyme (most drugs metabolised through P450)?
Tophi are most accurately described as?
Tophi are most accurately described as?
Aside from Allopurinol, which therapy requires extra caution in patents also prescribed azathioprine?
Aside from Allopurinol, which therapy requires extra caution in patents also prescribed azathioprine?
Which of the following is the correct starting point for initiating treatment?
Which of the following is the correct starting point for initiating treatment?
What is the function of Uricase?
What is the function of Uricase?
Which NSAIDs feature is most important for treatment?
Which NSAIDs feature is most important for treatment?
What is a known function of Interleukin 1?
What is a known function of Interleukin 1?
Which of the following is the normal range for uric acid to not develop gout?
Which of the following is the normal range for uric acid to not develop gout?
What is the purpose of Urate oxidase rasburicase?
What is the purpose of Urate oxidase rasburicase?
The patient is taking erythromycin, clarithromycin. What concern would there be in prescribing Colchicine?
The patient is taking erythromycin, clarithromycin. What concern would there be in prescribing Colchicine?
What is one difference of Febuxostat compared to Allopurinol? (Select all the apply)
What is one difference of Febuxostat compared to Allopurinol? (Select all the apply)
Which of the following is a conventional synthetic DMARD (csDMARD) used in the treatment of rheumatoid arthritis?
Which of the following is a conventional synthetic DMARD (csDMARD) used in the treatment of rheumatoid arthritis?
What is the primary mechanism of action of Abatacept in treating rheumatoid arthritis?
What is the primary mechanism of action of Abatacept in treating rheumatoid arthritis?
What is one potential adverse effect associated with anti-TNF-α agents used in the treatment of rheumatoid arthritis?
What is one potential adverse effect associated with anti-TNF-α agents used in the treatment of rheumatoid arthritis?
Which of the following is a potential adverse effect of JAK inhibitors?
Which of the following is a potential adverse effect of JAK inhibitors?
Which of the following is the target of Tocilizumab?
Which of the following is the target of Tocilizumab?
According to EULAR recommendations, what is the target in the 'treat-to-target' strategy for rheumatoid arthritis?
According to EULAR recommendations, what is the target in the 'treat-to-target' strategy for rheumatoid arthritis?
What is the mechanism of action of Rituximab in treating rheumatoid arthritis?
What is the mechanism of action of Rituximab in treating rheumatoid arthritis?
According to the Australian guidelines, which of the following combinations should be considered as a first-line therapy for rheumatoid arthritis?
According to the Australian guidelines, which of the following combinations should be considered as a first-line therapy for rheumatoid arthritis?
Which of the following is a key consideration when initiating DMARD therapy for rheumatoid arthritis?
Which of the following is a key consideration when initiating DMARD therapy for rheumatoid arthritis?
A patient with rheumatoid arthritis has been treated with methotrexate without adequate response. According to current guidelines, what is the next line of therapy?
A patient with rheumatoid arthritis has been treated with methotrexate without adequate response. According to current guidelines, what is the next line of therapy?
What is the primary reason for administering folic acid alongside methotrexate in the treatment of rheumatoid arthritis?
What is the primary reason for administering folic acid alongside methotrexate in the treatment of rheumatoid arthritis?
Compared to biological DMARDs (bDMARDs), how are targeted synthetic DMARDs (tsDMARDs) typically administered?
Compared to biological DMARDs (bDMARDs), how are targeted synthetic DMARDs (tsDMARDs) typically administered?
Which of the following statements accurately describes the action of low-dose methotrexate in treating rheumatoid arthritis?
Which of the following statements accurately describes the action of low-dose methotrexate in treating rheumatoid arthritis?
What should happen to DMARD doses when glucocorticoids are ceased in treatment of rheumatoid arthritis?
What should happen to DMARD doses when glucocorticoids are ceased in treatment of rheumatoid arthritis?
A patient on tofacitinib is older and a smoker, what risks are elevated?
A patient on tofacitinib is older and a smoker, what risks are elevated?
How does TNF-α primarily contribute to the pathogenesis of rheumatoid arthritis?
How does TNF-α primarily contribute to the pathogenesis of rheumatoid arthritis?
Which of these is a common adverse effect of tocilizumab? (Select all that apply)
Which of these is a common adverse effect of tocilizumab? (Select all that apply)
Rituximab is usually administered in what way?
Rituximab is usually administered in what way?
Which of the following agents is a biologic DMARD that acts as a soluble receptor?
Which of the following agents is a biologic DMARD that acts as a soluble receptor?
What is the risk of not prescribing folic acid with methotrexate?
What is the risk of not prescribing folic acid with methotrexate?
Unlike gout, what cells are present in the joint that will propagate the inflammatory signal in Rheumatoid Arthritis?
Unlike gout, what cells are present in the joint that will propagate the inflammatory signal in Rheumatoid Arthritis?
A patient is prescribed a drug that must bind to CD80/86 on antigen presenting cells to prevent them interacting with CD28 cells (“signal 2"). What drug is this?
A patient is prescribed a drug that must bind to CD80/86 on antigen presenting cells to prevent them interacting with CD28 cells (“signal 2"). What drug is this?
Rituximab does not affect what type of cell?
Rituximab does not affect what type of cell?
The development of which class of drugs significantly reduced the need for steroid use in treating rheumatoid arthritis?
The development of which class of drugs significantly reduced the need for steroid use in treating rheumatoid arthritis?
The introduction of which agents limited the advancement of the disease?
The introduction of which agents limited the advancement of the disease?
How frequent should a rheumatoid arthritis therapy be reviewed?
How frequent should a rheumatoid arthritis therapy be reviewed?
A patient being treated for Rhuematoid Arthritis develops herpes zoster. What agent is most likely the reason for this occurence?
A patient being treated for Rhuematoid Arthritis develops herpes zoster. What agent is most likely the reason for this occurence?
In the treatment of Rheumatoid Arthritis, how does IL-6 contribute to the destruction of joints?
In the treatment of Rheumatoid Arthritis, how does IL-6 contribute to the destruction of joints?
How can tolerance to Methotrexate be improved?
How can tolerance to Methotrexate be improved?
In assessing Rheumatoid Arthritis progression, what would the next step be if there is no obvious improvent after the first 3 months?
In assessing Rheumatoid Arthritis progression, what would the next step be if there is no obvious improvent after the first 3 months?
A patient presents with a suspected case of Rhuematoid Arthritis awaiting further testing. What option would not be considered with a Contraindication for using Methotrexate?
A patient presents with a suspected case of Rhuematoid Arthritis awaiting further testing. What option would not be considered with a Contraindication for using Methotrexate?
Methotrexate (MTX) is retained intracellularly in what forms?
Methotrexate (MTX) is retained intracellularly in what forms?
A Rheumatoid Arthritis therapy is reviewed after 6 months. What marker should be assessed during the review?
A Rheumatoid Arthritis therapy is reviewed after 6 months. What marker should be assessed during the review?
What component of the immune system do DMARDs target?
What component of the immune system do DMARDs target?
Which dose response of Methotrexate is used in Rheumatoid Arthritis management versus Chemotherapy. (Select all that apply)
Which dose response of Methotrexate is used in Rheumatoid Arthritis management versus Chemotherapy. (Select all that apply)
In a patient with previous Hepatitis B, which antibody from Rituximab has a significant, life threatening risk?
In a patient with previous Hepatitis B, which antibody from Rituximab has a significant, life threatening risk?
How does TNF-α stimulation causes Macrophages activate inflammation and survival.?
How does TNF-α stimulation causes Macrophages activate inflammation and survival.?
Methotrexate (MTX) has a long half life in ____ while shorter half life in ____.
Methotrexate (MTX) has a long half life in ____ while shorter half life in ____.
In deciding to use Oral medications, how do DMARD’s measure up against TNF??
In deciding to use Oral medications, how do DMARD’s measure up against TNF??
In rheumatoid arthritis, what is the primary target of the 'treat-to-target' (T2T) strategy according to EULAR recommendations?
In rheumatoid arthritis, what is the primary target of the 'treat-to-target' (T2T) strategy according to EULAR recommendations?
According to the information presented, what is typically recommended as the first-line DMARD for rheumatoid arthritis?
According to the information presented, what is typically recommended as the first-line DMARD for rheumatoid arthritis?
According to Australian guidelines, which combination therapy should be considered as a first-line treatment for rheumatoid arthritis?
According to Australian guidelines, which combination therapy should be considered as a first-line treatment for rheumatoid arthritis?
How often should a rheumatoid arthritis therapy be reviewed, especially if the target is not reached?
How often should a rheumatoid arthritis therapy be reviewed, especially if the target is not reached?
What class of DMARDs are monoclonal antibodies and related compounds classified as?
What class of DMARDs are monoclonal antibodies and related compounds classified as?
In the classification of DMARDs, what is characteristic of targeted synthetic DMARDs (tsDMARDs)?
In the classification of DMARDs, what is characteristic of targeted synthetic DMARDs (tsDMARDs)?
Concerning targeted therapies for Rheumatoid Arthritis, against what cells does Rituximab work?
Concerning targeted therapies for Rheumatoid Arthritis, against what cells does Rituximab work?
Which of the following best describes the mechanism of action of low-dose methotrexate (MTX) in treating rheumatoid arthritis?
Which of the following best describes the mechanism of action of low-dose methotrexate (MTX) in treating rheumatoid arthritis?
Why is folic acid typically administered with methotrexate in the treatment of rheumatoid arthritis?
Why is folic acid typically administered with methotrexate in the treatment of rheumatoid arthritis?
How is methotrexate usually dosed for the treatment of rheumatoid arthritis?
How is methotrexate usually dosed for the treatment of rheumatoid arthritis?
What is a significant consideration regarding the half-life of methotrexate when treating rheumatoid arthritis?
What is a significant consideration regarding the half-life of methotrexate when treating rheumatoid arthritis?
If a patient is prescribed tofacitinib, what risk factors can elevate the likelihood of adverse events?
If a patient is prescribed tofacitinib, what risk factors can elevate the likelihood of adverse events?
In the context of Anti-TNF-α agents, through which receptors does TNF-α primarily exert its effects?
In the context of Anti-TNF-α agents, through which receptors does TNF-α primarily exert its effects?
What is the primary mechanism by which TNF-α contributes to the pathology of rheumatoid arthritis?
What is the primary mechanism by which TNF-α contributes to the pathology of rheumatoid arthritis?
What should be checked for for latent or inactive tuberculosis (TB) before initiating treatment with anti-TNF-α agents?
What should be checked for for latent or inactive tuberculosis (TB) before initiating treatment with anti-TNF-α agents?
What is the mechanism of action of Tocilizumab in the treatment of rheumatoid arthritis?
What is the mechanism of action of Tocilizumab in the treatment of rheumatoid arthritis?
What is the route of administration and frequency of Tocilizumab to treat rheumatoid arthritis?
What is the route of administration and frequency of Tocilizumab to treat rheumatoid arthritis?
Why are JAK (Janus Kinase) inhibitors less targeted than biologic DMARDs (bDMARDs)?
Why are JAK (Janus Kinase) inhibitors less targeted than biologic DMARDs (bDMARDs)?
Which of the following adverse effects is particularly associated with JAK inhibitors used in rheumatoid arthritis treatment?
Which of the following adverse effects is particularly associated with JAK inhibitors used in rheumatoid arthritis treatment?
What is the mechanism of action of Abatacept in treating rheumatoid arthritis?
What is the mechanism of action of Abatacept in treating rheumatoid arthritis?
On what cells is CD80/86 found that allow Abatacept to inhibit T-Cell activation?
On what cells is CD80/86 found that allow Abatacept to inhibit T-Cell activation?
In addition to respiratory and UTI infections, which specific viral infection is particularly noted as an adverse effect of Abatacept?
In addition to respiratory and UTI infections, which specific viral infection is particularly noted as an adverse effect of Abatacept?
What is the mechanism of action of Rituximab in the treatment of rheumatoid arthritis?
What is the mechanism of action of Rituximab in the treatment of rheumatoid arthritis?
Which of the following is a significant adverse effect associated with Rituximab that necessitates screening before treatment?
Which of the following is a significant adverse effect associated with Rituximab that necessitates screening before treatment?
Early in the history of Rheumatoid Arthritis treatment, prior to the advent of DMARDs, what was the key limitation of available medications?
Early in the history of Rheumatoid Arthritis treatment, prior to the advent of DMARDs, what was the key limitation of available medications?
Which of the following is true regarding the initial use of glucocorticoids in treating rheumatoid arthritis?
Which of the following is true regarding the initial use of glucocorticoids in treating rheumatoid arthritis?
What is true regarding the efficacy of sulfasalazine, hydroxychloroquine and penicillamine, prior to the development of methotrexate?
What is true regarding the efficacy of sulfasalazine, hydroxychloroquine and penicillamine, prior to the development of methotrexate?
What is a common aetiological factor to both gout and rheumatoid arthritis?
What is a common aetiological factor to both gout and rheumatoid arthritis?
Which of the following is true regarding which gender is more affected by Rheumatoid Arthritis?
Which of the following is true regarding which gender is more affected by Rheumatoid Arthritis?
What is one difference between the development of rheumatoid arthritis and osteoarthritis?
What is one difference between the development of rheumatoid arthritis and osteoarthritis?
If methotrexate is ceased, what steps can be considered to improve the chance of continued remission??
If methotrexate is ceased, what steps can be considered to improve the chance of continued remission??
What is true about the first step when methotrexate is contraindicated?
What is true about the first step when methotrexate is contraindicated?
What is the key to decide if there is poor prognostic factors that require to add bDMARDS
What is the key to decide if there is poor prognostic factors that require to add bDMARDS
What is a likely side effect from Anti-IL6?
What is a likely side effect from Anti-IL6?
How do you make T cells more sensitive to apoptosis?
How do you make T cells more sensitive to apoptosis?
Which molecule does Abatacept target?
Which molecule does Abatacept target?
What is a risk associated to anti CD20 treatment (Rituximab)? (Select all that apply)
What is a risk associated to anti CD20 treatment (Rituximab)? (Select all that apply)
What is the normal dosing for weekly weight treatment for Methotrexate?
What is the normal dosing for weekly weight treatment for Methotrexate?
What is thought to be the impact of Adenosine?
What is thought to be the impact of Adenosine?
Which of the following best describes the primary characteristic of rheumatoid arthritis?
Which of the following best describes the primary characteristic of rheumatoid arthritis?
Which of the following joints are typically affected in rheumatoid arthritis, while sparing DIPs?
Which of the following joints are typically affected in rheumatoid arthritis, while sparing DIPs?
What is the strongest contributing factor to the aetiology of rheumatoid arthritis?
What is the strongest contributing factor to the aetiology of rheumatoid arthritis?
Which of the following best describes the cellular interactions in the pathophysiology of rheumatoid arthritis?
Which of the following best describes the cellular interactions in the pathophysiology of rheumatoid arthritis?
Which of the following is the most appropriate initial DMARD therapy for rheumatoid arthritis, according to the EULAR guidelines?
Which of the following is the most appropriate initial DMARD therapy for rheumatoid arthritis, according to the EULAR guidelines?
Which combination therapy does the Australian guidelines suggest as a first-line treatment for rheumatoid arthritis?
Which combination therapy does the Australian guidelines suggest as a first-line treatment for rheumatoid arthritis?
How frequently should rheumatoid arthritis therapy be reviewed if the treatment target is not achieved?
How frequently should rheumatoid arthritis therapy be reviewed if the treatment target is not achieved?
Which category of DMARDs includes monoclonal antibodies and related compounds?
Which category of DMARDs includes monoclonal antibodies and related compounds?
Which of the following is a characteristic that defines targeted synthetic DMARDs (tsDMARDs)?
Which of the following is a characteristic that defines targeted synthetic DMARDs (tsDMARDs)?
Which of the following best defines the mechanism of action of low-dose methotrexate in treating rheumatoid arthritis?
Which of the following best defines the mechanism of action of low-dose methotrexate in treating rheumatoid arthritis?
Why is folic acid commonly administered with methotrexate in the treatment of rheumatoid arthritis?
Why is folic acid commonly administered with methotrexate in the treatment of rheumatoid arthritis?
What is a significant consideration when administering weekly methotrexate for rheumatoid arthritis?
What is a significant consideration when administering weekly methotrexate for rheumatoid arthritis?
What is increased when a patient on tofacitinib older and a smoker?
What is increased when a patient on tofacitinib older and a smoker?
Through which receptors does TNF-α primarily exert its effects?
Through which receptors does TNF-α primarily exert its effects?
What specific screening is essential before initiating treatment with anti-TNF-α agents?
What specific screening is essential before initiating treatment with anti-TNF-α agents?
Which of the following best describes the mechanism of action of Tocilizumab in treating rheumatoid arthritis?
Which of the following best describes the mechanism of action of Tocilizumab in treating rheumatoid arthritis?
Concerning the administration of tocilizumab, what are the common routes?
Concerning the administration of tocilizumab, what are the common routes?
Why are JAK (Janus Kinase) inhibitors described as less targeted than biologic DMARDs (bDMARDs)?
Why are JAK (Janus Kinase) inhibitors described as less targeted than biologic DMARDs (bDMARDs)?
Increased of what infection is particular linked to the adverse effects of JAK inhibitors used in the treatment of rheumatoid arthritis?
Increased of what infection is particular linked to the adverse effects of JAK inhibitors used in the treatment of rheumatoid arthritis?
What cells express CD80/86 allowing Abatacept to bind and inhibit T-cell activation?
What cells express CD80/86 allowing Abatacept to bind and inhibit T-cell activation?
Which specific viral infection is particularly associated as an adverse effect of Abatacept?
Which specific viral infection is particularly associated as an adverse effect of Abatacept?
What screening is required before treating patients with Rituximab?
What screening is required before treating patients with Rituximab?
Prior to the advent of DMARDs in Rheumatoid Arthritis what was the biggest limitation in managing symptoms?
Prior to the advent of DMARDs in Rheumatoid Arthritis what was the biggest limitation in managing symptoms?
Which of the following is true regarding corticosteroids?
Which of the following is true regarding corticosteroids?
What statement is most correct of pre-methotrexate treatments?
What statement is most correct of pre-methotrexate treatments?
Concerning Rheumatoid Arthritis, which gender is more affected?
Concerning Rheumatoid Arthritis, which gender is more affected?
How is Rheumatoid Arthritis different to Osteoarthritis?
How is Rheumatoid Arthritis different to Osteoarthritis?
Methotrexate is an important DMARD in patients with RA. If MTX fails or is contraindicated, what is the next step in management?
Methotrexate is an important DMARD in patients with RA. If MTX fails or is contraindicated, what is the next step in management?
A Rheumatoid Arthritis therapy is reviewed after 3 months. What would be considered as a prompt to escalate therapy?
A Rheumatoid Arthritis therapy is reviewed after 3 months. What would be considered as a prompt to escalate therapy?
What common side effect can be expected from Anti-IL6 agents?
What common side effect can be expected from Anti-IL6 agents?
How is it though Methotrexate increases T cell sensitivity to apoptosis?
How is it though Methotrexate increases T cell sensitivity to apoptosis?
Which cells do Abatacept target?
Which cells do Abatacept target?
A patient is taking Rituximab, which of the following are some risks that can occur? (Select all that apply)
A patient is taking Rituximab, which of the following are some risks that can occur? (Select all that apply)
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Study Notes
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Rheumatoid arthritis is a chronic, destructive autoimmune disease
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Most common autoimmune arthritis, affecting ~2% of Australians, can lead to rheumatoid nodules, vasculitis, parenchymal lung disease, coronary effects, secondary renal effects, and Felty's syndrome (splenomegaly)
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Rheumatoid arthritis presents with articular, extra-articular, and systemic features
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Rheumatoid arthritis is a chronic inflammatory arthropathy
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Women are 2-3 times more commonly affected by rheumatoid arthritis, while men are 3 more commonly affected by gout
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Joint pain worsens over weeks to months in rheumatoid arthritis, unlike gout with rapid onset
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Polyarticular involvement is common, especially in hands, wrists, and feet, with rheumatoid arthritis unlike monoarticular presentation of gout
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Rheumatoid arthritis is an autoimmune disorder, whereas osteoarthritis is degenerative
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Development worsens over weeks to months, unlike osteoarthritis that gradually develops over years
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Small joints are initially affected in rheumatoid arthritis, skipping lumbar and thoracic spine
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MCP and PIP joints, along with MTP joints, are affected but spares DIPs
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Joint pain and stiffness are accompanied by systemic and extra-articular symptoms in rheumatoid arthritis, unlike the joint-related symptoms in osteoarthritis
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Rheumatoid arthritis presents with morning joint stiffness with swelling; osteoarthritis is milder with minimal swelling
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Exact cause remain unknown
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Women are affected two to three times more than men
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Significant genetic factors play a role, with family history increasing risk [x3 for 1st relative, x2 2nd relative]
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Association with HLA-DRB1 (RA motif) and >100 other genes
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Environmental factors like smoking and obesity contribute
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RA development involves initiation of autoimmunity
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Progression starts with susceptibility, then asymptomatic autoimmunity, early symptomatic autoimmunity, undifferentiated arthritis, leading to classifiable RA
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Cytokines and chemokines and immune cells are observed
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Unlike gout, where neutrophils play a big role, RA has more cells from the adaptive immune system, which propagate the inflammatory signal
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Fibroblast-like synoviocytes are adaptive
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Macrophages and APCs (innate) as well as T and B cells (adaptive) play a role
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Nature Reviews / Disease Primers; Smolen et al. 2018 provides a key diagram
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The first-line conventional synthetic DMARD, Low dose methotrexate mechanism involves parent and polyglutamate metabolites inhibit different intracellular enzymes
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It increases intracellular and extracellular adenosine, which has anti-inflammatory results via multiple mechanisms, including reduced inflammatory cytokines and increased anti-inflammatory cytokines and change in cellular responses
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Rapidly dividing cells must have folate to survive
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vs high dose (chemotherapy), the drug inhibits DNA and RNA synthesis by depleting intracellular folate, is cytotoxic
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In lupus, sulfasalazine, hydroxychloroquine, penicillamine may be used to reduce the need for steroids
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Glucocorticoids are able to better control the inflammatory nature of the disease with less side effects
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EULAR treatment guidelines follows treat to target for sustained remission or disease activity
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Methotrexate is first line, with leflunomide or sulfasalazine as alternatives
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Triple therapy of methotrexate + sulfasalazine + hydroxychloroquine, or with bDMARD/tsDMARD may be used to lower doses of each individual drug and avoid the need of next line therapy
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Review every 1-3 months, change if no improvement <3 months or target not reached by 6 months
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Add in biological DMARDs (b) or targeted synthetic DMARDs (ts) as a secondary option
DMARDs
- Conventional synthetic DMARDs (cs): methotrexate, leflunomide, sulfasalazine
- Biological DMARDs (b): monoclonal antibodies and related compounds, proteins
- Targeted synthetic DMARDs (ts): newer agents and JAK inhibitors
Low dose methotrexate (MTX)
- Weekly dosing of 5-25mg should be titrated to effect/tolerability
- Intramuscular, subcutaneous dosing also available/recommended if poor PO
- The long half life helps maintain its therapeutic effect
- Concurrent folic acid prevents toxicity
- Typical dose is 5-10mg/week, or 0.5mg daily except for day of MTX dose
- Cases of fatality reported without proper dosing and adequate supplemental folic acid
- Calcium folinate addresses supratherapeutic dose with MTX
- Adverse events include bone marrow suppression (esp. without folate), GIT issues, hepatotoxicity
- High risk Category X category when pregnant
Anti-TNF-α agents
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They include IV infliximab and SC infliximab, adalimumab, etanercept, golimumab, certolizumab pegol
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TNF-α regulates immune cells, produced mainly by macrophages
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Acts via TNFR1 (all cells) and TNFR2 (more restricted including immune cells), with downstream pathways involving stimulation of macrophages, T cell proliferation + suppression of Tregs
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Infliximab is a chimeric monoclonal antibody, adalimumab and golimumab are immune-directed human monoclonal antibody, certolizumab pegol is a humanised monoclonal antibody
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Etanercept TNF-a receptor 2 is a nervous system-directed soluble receptor
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TNF is essential in granuloma formation and maintenance.
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Adverse effects include immune suppression, increased risk of malignancies (lymphoma) and drug-induced lupus
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Check hepatitis B levels
Anti-IL-6
- Act to counter IL-6 effects
- IL-6 has many results including, acute phase reaction, B cell autoantibody production, T cell activation, and osteoclast activation
- Tocilizumab inhibits key inflammatory pathways
- Tocilizumab, a SC formulation for RA and IV, targeting the IL-6 receptor alpha
- Adverse events include injection related reactions, LFT abnormalities, but is less immunosuppressive
- Binds to IL-1 receptors
JAK inhibitors
- Janus kinase (JAK1, JAK2, JAK3, and Tyk2) are associated with a large number of cytokine receptors which are involved in signalling of inflammatory cells
- Baricitinib (JAK1, JAK2) and tofacitinib (JAK1, JAK3>JAK2) are oral treatments
- The oral surveillance trial with Tofacitinib had 4,362 patients
- Dangers include infections, herpes zoster, cardiovascular issues, dyslipidaemia, venous thromboembolism, malignancy, non-melanoma skin cancer, and haematological issues, neutropaenia, lymphopaenia and anaemia
- One JAK must have multiple cytokine signals
- JAK2 is more haematopoietic, thus less targeted in autoimmune cases
Anti-TNF risks
- There are increased rates of malignancy, major adverse cardiovascular events (MACE) reported
- Should not use in patients <65 y.o. and previous, or current smokers because of risk of VTE
- There is not a consensus regarding the relative risks of these agents
Other agents
- Abatacept works via extracellular domain of CTLA4 bound to Fc portion of IgG, binding to CD80/86 on antigen presenting cells and blocking interaction with CD28 ("signal 2”), given SC weekly, or IV, if not on PBS
- Infections are the main concern
B cell treatment
- Rituximab (anti-CD20), Tumor-directed chimeric monoclonal antibody results in B cell death, but does not affect plasma cells, administered via IV infusions
- Not restricted to PBS requirements
- Adverse effects include infusion related reactions, infections (including opportunistic infections), hepatitis B reactivation, hypogammaglobulinemia, PML (rare)
- Screened for HBV (core)
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