Rheumatoid arthritis Flashcards
Rheumatoid arthritis is a chronic systemic inflammatory disease that causes persistent (?) joint synovitis (inflammation of the synovial membrane) typically of the small joints of the hands and feet, although any synovial joint can be affected.
symmetrical
Rheumatoid arthritis is a chronic systemic inflammatory disease that causes persistent symmetrical joint (?) (inflammation of the synovial membrane) typically of the small joints of the hands and feet, although any synovial joint can be affected.
synovitis
What is the definition of synovitis?
Inflammation of the synovial membrane
Rheumatoid arthritis is a chronic systemic inflammatory disease that causes persistent symmetrical joint synovitis (inflammation of the synovial membrane) typically of the (small/large?) joints of the hands and feet, although any synovial joint can be affected.
small
What is the name of the rare form of inflammatory arthritis which causes attacks of joint pain and swelling similar to rheumatoid arthritis, but the joints return to normal in between attacks?
Palindromic rheumatism
Patients with palindromic rheumatism may later develop rheumatoid arthritis
What is the first-line treatment in patients with newly diagnosed active rheumatoid arthritis?
Monotherapy with a conventional DMARD
- Oral methotrexate, leflunomide or sulfasalazine
Hydroxychloroquine sulfate, a weak conventional DMARD, is an alternative in patients with mild rheumatoid arthritis or those with palindromic rheumatism
When should you start treatment with a DMARD in patients with newly diagnosed active rheumatoid arthritis?
As soon as possible, ideally within 3 months of onset of persistent symptoms
Conventional DMARDs have a (fast/slow?) onset of action and can take 2–3 months to take effect.
Slow
Consider short-term bridging treatment with a corticosteroid (by oral, intramuscular, or intra-articular administration) when starting treatment with a new conventional DMARD to provide rapid symptomatic control, while waiting for the new DMARD to take effect.
Conventional DMARDs have a slow onset of action and can take (?) months to take effect.
2-3
Consider short-term bridging treatment with a corticosteroid (by oral, intramuscular, or intra-articular administration) when starting treatment with a new conventional DMARD to provide rapid symptomatic control, while waiting for the new DMARD to take effect.
What should you also prescribe when starting a patient with newly diagnosed active rheumatoid arthritis with a conventional DMARD?
Short-term bridging corticosteroid
To provide rapid symptomatic control while waiting for the new DMARD to take effect
What should be given to rapidly decrease inflammation during flare-ups of rheumatoid arthritis?
Short-term corticosteroids
If treatment target (remission or low disease activity) for rheumatoid arthritis has not been achieved despite dose escalation on conventional DMARDs, what is the next step in management?
Offer combination therapy with additional conventional DMARDs
(oral methotrexate, leflunomide, sulfasalazine or hydroxychloroquine sulfate)
What drugs are considered for monotherapy with conventional DMARDs in the treatment of rheumatoid arthritis? (3)
Methotrexate
Leflunomide
Sulfasalazine
Hydroxychloroquine sulfate is a week conventional DMARD and is an alternative in patients with mild rheumatoid arthritis or those with palindromic rheumatism
What are the drugs that are considered when treating rheumatoid arthritis with combination therapy of conventional DMARDS? (4 conventional DMARDs to choose from)
Methotrexate
Leflunomide
Sulfasalazine
Hydroxychloroquine sulfate
What are the three treatment options if there has been an inadequate response to combination therapy with conventional DMARDs for the treatment of rheumatoid arthritis?
- Tumour necrosis factor (TNF) alpha inhibitor
- Biological DMARD (abatacept, sarilumab or tocilizumab)
- Targeted synthetic DMARD (baricitinib, filgotinib, tofacitinib or upadactinib)
Adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab are all examples of which class of drug?
Tumour necrosis factor (TNF) alpha inhibitors
Abatacept, sarilumab, or tocilizumab are all examples of which class of drug?
Biological DMARDs
Baricitinib, filgotinib, tofacitinib, or upadacitinib are all examples of which class of drug?
Targeted synthetic DMARDs
Methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine sulfate are all examples of which class of drug?
Conventional DMARDs
Which treatment is an option for patients with severe active rheumatoid arthritis who have had an inadequate response to, or are intolerant of other DMARDs, including at least one TNF alpha inhibitor?
Rituximab + methotrexate
What is the last resort treatment for rheumatoid arthritis that should only be used if all other treatments options (including biological and targeted synthetic DMARDs) have been offered?
Long-term corticosteroid use
Patients with active rheumatoid arthritis should be monitored (1?) until the treatment target (either remission or low disease activity) has been achieved, and all patients with rheumatoid arthritis should be reviewed (2?)
- Monthly
2. Annually
What is the treatment target for rheumatoid arthritis?
Disease remission
OR
Low disease activity if remission cannot be achieved
What additional short-term pain relief should be considered for control of pain and stiffness associated with rheumatoid arthritis? (2)
NSAID
or
Selective COX-2 inhibitor
Patients should be offered a PPI to minimise associated GI adverse effects
When is surgery considered an option in the treatment of rheumatoid arthritis? (4)
- Drug treatment has failed to adequately manage persistent pain due to joint damage or other identifiable soft tissue causes
- Worsening of joint function,
- Progressive deformity
- Persistent localised synovitis
What are the two indications for the use of abatacept?
Moderate-to-severe active rheumatoid arthritis (specialist use only)
Active psoriatic arthritis (specialist use only)
Abatacept is a biological DMARD
What is the contraindication for the use of the biological DMARD, abatacept?
Severe infection
Caution: do not initiate until active infections are controlled
For how long must a patient taking the biological DMARD abatacept ensure effective contraception?
During treatment and for 14 weeks after last dose
What class of drug is abatacept?
Biological DMARD
What class of drug is adalimumab?
TNF alpha inhibitor
What are the contraindications for the use of the TNF alpha inhibitor adalimumab?
Moderate or severe heart failure
Severe infections
For how long must a patient taking the TNF alpha inhibitor adalimumab ensure effective contraception?
During treatment and for at least 5 months after last dose
What does a patient need to be screened for prior to starting treatment with TNF alpha inhibitor adalimumab?
Tuberculosis (TB) (active and latent)
What needs to be monitored for in a patient taking the TNF alpha inhibitor adalimumab?
- Infection (before, during and or 4 months after treatment)
- Non-melanoma skin cancer before and during treatment
- Pre-existing or developing central demyelinating disorders (before and at regular intervals during treatment)
(?) is metabolised to mercaptopurine.
Azathioprine
Azathioprine is metabolised to (?).
mercaptopurine
Is azathioprine commonly used in the treatment of rheumatoid arthritis?
No
Due to the availability of newer, more effective drugs
Azathioprine is an older conventional DMARD
What are the common side effects of the older conventional DMARD azathioprine? (5)
Bone marrow depression (dose-related) Infection Leucopenia Pancreatitis Thrombocytopenia
If a transplant patient taking the older conventional DMARD azathioprine falls pregnant, should they stop taking azathioprine?
NO
Transplant patients immunosuppressed with azathioprine should not discontinue it on becoming pregnant. However, there have been reports of premature birth and low birth-weight following exposure to azathioprine, particularly in combination with corticosteroids. Spontaneous abortion has been reported following maternal or paternal exposure.
What does a patient need to be screened for prior to starting treatment with the older conventional DMARD azathioprine?
Thiopurine methyltransferase (TPMT) activity
The enzyme thiopurine methyltransferase (TPMT) metabolises thiopurine drugs (azathioprine, mercaptopurine, tioguanine); the risk of myelosuppression is increased in patients with reduced activity of the enzyme, particularly for the few individuals in whom TPMT activity is undetectable.
Why does thiopurine methyltransferase (TPMT) activity need to be screened prior to starting treatment with the older conventional DMARD azathioprine?
Increased risk of myelosuppression in patients with reduced activity of TPMT
Name three drugs in which you should measure thiopurine methyltransferase (TPMT) activity prior to starting therapy?
Azathioprine
Mercaptopurine
Tioguanine
Seek specialised advice for those with reduced or absent TPMT activity
What do you need to monitor for in a patient taking the older conventional DMARD azathioprine? (3)
- Toxicity
- FBC weekly for first 4 weeks, then reduce to at least every 3 months
- Signs of myelosuppression
What class of drug is baricitinib?
Targeted synthetic DMARD
Baricitinib selectively and reversibly inhibits the Janus-associated tyrosine kinases JAK1 and JAK2.
What are the two indications for the use of the targeted synthetic DMARD baricitinib?
Moderate-to-severe active rheumatoid arthritis
Moderate-to-severe atopic eczema
What is an uncommon but important side effect of the targeted synthetic DMARD baricitinib that will lead to permanent discontinuation if it occurs?
VTE
What should be screened for prior to starting treatment with the targeted synthetic DMARD baricitinib? (2)
Tuberculosis (TB)
Viral hepatitis
What class of drug is certolizumab pegol?
TNF alpha inhibitor
What are the contraindications to the use of the TNF alpha inhibitor certolizumab pegol? (2)
Moderate to severe heart failure
Severe active infection
What needs to be screened for prior to starting treatment with the TNF-alpha inhibitor certolizumab pegol?
Tuberculosis (TB)
Is ciclosporin commonly used in the treatment of rheumatoid arthritis?
NO
No longer used commonly due to the availability of newer, more effective drugs
(?) inhibits production and release of lymphokines, thereby suppressing cell-mediated immune response.
Ciclosporin
Pomelo juice is predicted to (1?) ciclosporin exposure.
Purple grape juice is predicted to decrease ciclosporin exposure.
- increase
Pomelo juice is predicted to increase ciclosporin exposure.
Purple grape juice is predicted to (1?) ciclosporin exposure.
- decrease
(?) juice is predicted to increase ciclosporin exposure.
Purple grape juice is predicted to decrease ciclosporin exposure.
Pomelo
Pomelo juice is predicted to increase ciclosporin exposure.
(?) juice is predicted to decrease ciclosporin exposure.
Purple grape
What class of drug is etanercept?
TNF alpha inhibitor
What is the contraindication for the use of the TNF alpha inhibitor etanercept?
Active infection
For how long must a patient taking the TNF alpha inhibitor etanercept ensure effective contraception?
During treatment and for 3 weeks after last dose
What should be screened for prior to starting treatment with the TNF alpha inhibitor etanercept?
Tuberculosis (TB)
What needs to be monitored for during treatment with the TNF alpha inhibitor etanercept?
Skin cancer
Monitor for skin cancer before and during treatment, particularly in those at risk (including patients with psoriasis or a history of PUVA treatment).
What class of drug is filgotinib?
Targeted synthetic DMARD
Filgotinib is a selective inhibitor of the Janus-associated tyrosine kinase JAK1.
What is the only indication for the use of the targeted synthetic DMARD filgotinib?
Rheumatoid arthritis
What are the contraindications for the use of the targeted synthetic DMARD filgotinib? (5)
- Absolute lymphocyte count less than 0.5 x 10^9 cells/litre
- Absolute neutrophil count less than 1 x 10^9 cells/litre
- Haemoglobin less than 8 g/dL
- Serious infection (active)
- Tuberculosis (active)
For how long must a female patient taking the targeted synthetic DMARD filgotinib ensure effective contraception?
During treatment for at least 1 week after stopping treatment
What must a male patient be warned about prior to starting treatment with the targeted synthetic DMARD filgotinib?
Potential risk of reduced fertility or infertility
No effects on female fertility have been observed in animal studies
What needs to be screened for prior starting treatment with the targeted synthetic DMARD filgotinib? (2)
Tuberculosis (TB)
Viral hepatitis
What class of drug is golimumab?
TNF alpha inhibitor
What are the two contraindications for the use of the TNF-alpha inhibitor golimumab?
Moderate or severe heart failure
Severe active infection
What pre-treatment is required prior to starting therapy with the TNF-alpha inhibitor golimumab?
Tuberculosis (TB)
What are the three indications for the use of the weak conventional DMARD hydroxychloroquine sulfate?
Active rheumatoid arthritis
Systemic and discoid lupus erythematosus
Dermatological conditions caused or aggravated by sunlight
(drug?) is a weak conventional DMARD
Hydroxychloroquine sulfate
Hydroxychloroquine sulfate is a (?) conventional DMARD
weak
Hydroxychloroquine sulfate is a weak (?)
conventional DMARD
What needs to be monitored regularly in a patient taking hydroxychloroquine sulfate?
Opthalmological examination (monitoring for retinopathy)
Recommendations:
- baseline examination (fundus photography and spectral domain optical coherence tomography) within 6-12 months of treatment initiation
- Annual monitoring if taken hydroxychloroquine for > 5 years
- Annual monitoring may be commenced before 5 years of treatment if additional risk factors
What are the common side effects of hydroxychloroquine sulfate? (9)
Abdominal pain Appetite decreased Diarrhoea Emotional lability Headache Nausea Skin reactions Vision disorders Vomiting
What is an uncommon side effect of hydroxychloroquine sulfate that must be monitored for?
Retinopathy
If a patient with rheumatoid arthritis taking hydroxychloroquine becomes pregnant, do you need to stop this antimalarial drug?
No, if the rheumatic disease is well controlled
But advised to avoid using during pregnancy
To avoid excessive dosage in (?) patients, the dose of hydroxychloroquine should be calculated on the basis of ideal body-weight.
obese
To avoid excessive dosage in obese patients, the dose of hydroxychloroquine should be calculated on the basis of (?).
ideal body weight
What class of drug is infliximab?
TNF alpha inhibitor
What are the two contraindications for the use of the TNF-alpha inhibitor infliximab?
Moderate to severe heart failure
Severe infections
Why must resuscitation equipment be available for immediate use during the infusion of the TNF-alpha inhibitor infliximab?
Risk of hypersensitivity reactions
All patients should be observed carefully for 1–2 hours after infusion and resuscitation equipment should be available for immediate use (risk of hypersensitivity reactions).
What pre-treatment screening is required before starting a patient on the TNF-alpha inhibitor infliximab?
Tuberculosis (TB)
What class of drug is leflunomide?
Conventional DMARD
What are the two indications for the use of the conventional DMARD leflunomide?
Moderate-to-severe active rheumatoid arthritis
Active psoriatic arthritis
What are the three contraindications for the use of the conventional DMARD leflunomide?
Serious infection
Severe hypoproteinaemia
Severe immunodeficiency
The conventional DMARD leflunomide has a (long/short?) half-life
long
Which potentially life-threatening side effect of leflunomide (conventional DMARD) usually occurs in the first 6 months of treatment?
Hepatotoxicity
Leflunomide (conventional DMARD): Effective contraception essential during treatment and for at least (1?) years after treatment in women and at least (2?) months after treatment in men (plasma concentration monitoring required; waiting time before conception may be reduced with washout procedure
- 2 years
2. 3 months
What pre-treatment screening is required prior to starting a patient on the conventional DMARD leflunomide in women?
Pregnancy (must be excluded)
What monitoring is required during treatment with the conventional DMARD leflunomide? (3)
FBC
LFTs
BP
Due to the long half-life of leflunomide (conventional DMARD), what two things can be given to aid drug elimination in case of serious adverse effects or before starting another DMARD (washout period)?
Colestyramine
OR
Activated charcoal
What class of drug is methotrexate?
Conventional DMARD
Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.
Methotrexate inhibits the enzyme (?), essential for the synthesis of purines and pyrimidines.
dihydrofolate reductase
Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of (?) and (?).
Purines
Pyrimidines
(?) inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.
Methotrexate
What are the indications for the use of the conventional DMARD methotrexate? (4)
- Severe Crohn’s disease (including maintenance of remission)
- Moderate to severe active rheumatoid arthritis
- Neoplastic diseases
- Severe psoriasis unresponsive to conventional therapy
How often is a dose of methotrexate given in autoimmune conditions?
once weekly
What are the contraindixcations for the use of the conventional DMARD methotrexate?
Active infection
Ascites
Immunodeficiency syndromes
Significant pleural effusions
What can you give to reduce the mucosal and GI side-effects of methotrexate?
Folic acid
Give folic acid to reduce side-effects. Folic acid decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity; there is no evidence of a reduction in haematological side-effects.
What may be the first sign of GI toxicity in a patient taking methotrexate?
Ulcerative stomatitis
Withdraw treatment
How long does a patient require effective contraception when taking and stopping methotrexate?
During treatment and for at least 6 months after treatment in MEN and WOMEN
Can a mother breastfeed while taking methotrexate?
NO
Present in milk
What pre-treatment screening is required before starting treatment with methotrexate? (3)
Exclude pregnancy
FBC
LFTs
What needs to be monitored regularly in a patient taking methotrexate?
FBC
Renal function
LFTs
Every 1-2 weeks until therapy stabilised, thereafter every 2-3 months
Patients taking methotrexate must be advised to report all symptoms and signs suggestive of (?)
Infection
Especially sore throat
Treatment with (?) may be required in acute toxicity of methotrexate
folinic acid (as calcium folinate)
Is penicillamine commonly used in the treatment of rheumatoid arthritis?
No
Due to the availability of newer, more effective drugs
(?) aids the elimination of copper ions in Wilson’s disease (hepatolenticular degeneration)
Penicillamine
Penicillamine aids the elimination of (?) in Wilson’s disease (hepatolenticular degeneration).
copper ions
Penicillamine aids the elimination of copper ions in (?) (hepatolenticular degeneration).
Wilson’s disease
What class of drug is sarilumab?
Biological DMARD
Sarilumab is a recombinant human monoclonal antibody that specifically binds to interleukin-6 receptors and blocks the activity of pro-inflammatory cytokines.
What pre-treatment screening is required before starting a patient on the biological DMARD sarilumab?
Tuberculosis (TB)
What class of drug is sulfasalazine?
Conventional DMARD
And an aminosalicylate
What are the indications for the use of sulfasalazine? (3)
Ulcerative colitis
Active Crohn’s disease
Active rheumatoid arthritis
What needs to be monitored in a patient taking sulfasalazine? (3)
FBC
Renal function
Liver function
What class of drug is tocilizumab?
Biological DMARD
What class of drug is tofacitinib?
Targeted synthetic DMARD
Tofacitinib selectively inhibits the Janus-associated tyrosine kinases JAK1 and JAK3.
What class of drug is upadacitinib?
Targeted synthetic DMARD
Upadacitinib is a selective and reversible inhibitor of the Janus-associated tyrosine kinase JAK1.
