Rheumatoid Arthritis Flashcards
What type of disorder is rheumatoid arthritis (RA)?
What does it cause to the joints?
It is an inflammatory autoimmune disorder which leads to painful & disabling joints
What is the cause of death in patients with RA?
CVD, because the inflammatory mediators associated with RA also speed up atherosclerosis = CVD
Why is RA considered immunological?
Because the body produces antibodies against RA
Which gender are more prone to RA?
Females
What types of environment is RA more likely to be in?
Urban environments (city), not rural
What happens in the joints to cause RA?
The synovium of the joint gets infiltrated by chronic inflammatory cells (e.g. lymphocytes, plasma cells, cytokines).
This causes the inflammatory mediators to all migrate to the synovium & create their own environment, forming a tumour (called a pannus).
The centre of this tumour is necrotic.
Who is the patient referred to if they have suspected RA?
A rheumatologist.
What are the symptoms of RA?
- Pain/stiffness/swelling of small joints of hands/feet
- Hammer toes
- Swollen wrist joints
- Other joint deformities
What does palindromic pain mean?
When the pain comes & goes.
What is bursitis?
Bursa is a lubricating fluid between the tendon & the bone. When this is infected, you get bursitis.
What conditions are RA patients more at risk of developing?
- Osteoporosis
- Anaemia
- Depression
- CVD
- Dry eye syndrome
What are the non-drug treatment options for RA?
- Patient education
- Surgery
- Physiotherapists
- Support groups
Why is paracetamol not an ideal option to give in RA?
Because paracetamol is not non-inflammatory, so not ideal.
NSAIDs are more appropriate.
Why are NSAIDs & COX 2 inhibitors given in RA?
They are effective in relieving joint pain/stiffness. They are used to control the symptoms, not cure.
Do NSAIDs inhibit COX 1, or COX 2 enzymes (or both)?
Both.
Why do NSAIDs produce GI side effects?
Because NSAIDs inhibit COX-1, which produces PGE2 (protecting the gastric mucosa). NSAIDs hence inhibit this.
Which COX enzyme is induced by inflammation?
COX-2
Why are corticosteroids powerful anti-inflammatory drugs?
Because they inhibit phospholipase A2, so arachidonic acid formation is also inhibited & this blocks all inflammatory pathways.
Why are corticosteroids useful in asthmatics?
Lipooxygenases create leukotrienes which cause broncho-constriction.
By inhibiting this pathway with a corticosteroid, leukotriene formation is inhibited = beneficial in asthmatics
What drug is always given with a steroid?
A PPI.
What drug is given if a patient has had a previous ulcer history, but no CVD?
A COX-2 inhibitor.
Do NSAIDs or COX 2 inhibitors cause a higher CV risk?
COX 2 inhibitors
What are examples of COX-2 inhibitors?
Etoricoxib, or celecoxib
Which 2 NSAIDs provide CV protectivity (include doses)?
- Naproxen 1g
2. Ibuprofen max. 1.2g (low doses only)
What is the actual maximum dose of ibuprofen which cannot be used in RA due to CV risks?
2.4g.
That is why 1.2g is the max. safest dose.
Do you start with ibuprofen or naproxen first in RA?
Ibuprofen 1.2g.
If patient is intolerant, then switch to naproxen 1g (with a PPI)
Which type of antipsychotic drugs should never be given with an NSAID?
An SSRI, because with NSAIDs they increase anti-platelet effects = higher risk of bleeding.
What are some side effects of NSAIDs/COX 2 inhibitors, besides GI discomfort?
- Worsening of asthma
- Fluid retention
- Renal failure
- Higher BP
When are corticosteroids given in RA?
Only during flare ups as they have rapid anti-inflammatory effects.
What are some side effects of corticosteroids?
- Weight gain
- Diabetes
- Depression
- Increased BP - from fluid retention
- GI side effects
Which corticosteroid (with dose) is given to RA patients, & for how long?
Prednisolone 7.5mg daily for 2-3 years.
Which corticosteroid can be used as a local injection into the joint?
Hydrocortisone acetate.
What are DMARDs & when should they be used in RA?
DMARDs: Disease Modifying Anti-Rheumatic Drugs
They are drugs which inhibit inflammatory cytokines & slow down joint erosion.
They should be used as early as possible to prevent irreversible joint effects of the disease.
What are the 4 conventional DMARDs which can be used in RA?
- Methotrexate
- Sulfasalazine
- Leflunomide
- Hydroxychloroquine
Which DMARD is given to women who are planning on getting pregnant?
Sulfasalazine
Which cDMARD must be given with long-term contraception?
Leflunomide.
What drugs are given in step 1 treatment of RA?
Methotrexate (MTX) + short-term prednisolone 7.5mg
If MTX intolerated, start with any other cDMARD (leflunomide, sulfasalazine, or hydroxychloroquine)
What side effects should RA patients report if they are taking sulfasalazine?
Why should they be reported?
- Bleeding
- Unexpected bruising
- Sore throat/fever
They should be reported because sulfasalazine reduces WBCs, which can lead to further blood disorders.
What is the dose of sulfasalazine?
Start 500mg daily, increased by 500mg weekly until 2-3g daily.
What close monitoring should be done when taking sulfasalazine?
FBC count + platelet count
What is the dosing of methotrexate?
7.5mg weekly by mouth, max. 20mg /week.
What is the mechanism of action of methotrexate?
What does this deplete the levels of?
It inhibits the enzyme dihydrofolate reductase, which reduces folic acid levels in the body
What should be given alongside methotrexate (include dose)?
Folic acid 5mg (not taken on the same day as methotrexate)
This is given to reduce side effects of MTX
What monitoring should be done with methotrexate?
- FBC count
2. Renal & liver function tests
Why should NSAIDs/aspirin never be given with methotrexate?
Because NSAIDs/aspirin inhibit the renal excretion of MTX, causing toxicity.
What is the only methotrexate tablet dose available?
2.5mg tablets.
What specific side effect should RA patients taking methotrexate look out for?
Shortness of breath, because it can cause pulmonary toxicity
Which cDMARD can cause retinopathy & hence needs regular eye screenings?
Hydroxychloroquine
Why isn’t sodium aurothiomalate & auronofin (both gold) given as treatment in RA?
Due to many adverse side effects.
When can ciclosporin be given in RA?
When second line treatment is ineffective
Which cDMARD has the quickest onset of action (4-6 weeks)?
Leflunomide.
What are some side effects of leflunomide?
- Increased BP
- Hepatotoxicity
- Increased risk of infections
- Bone marrow toxicity
What is step 2 of RA treatment, if methotrexate alone hasn’t worked?
You add a second cDMARD (leflunomide/sulfasalazine) + prednisolone 7.5mg
When do you add a biological DMARD or JAK inhibitor in RA treatment?
If methotrexate + other cDMARD has not worked.
What is the DAS28 score?
It is a measure of disease activity in RA.
- DAS28: Disease Activity Score (28 joints in our body)
- You will get a score /10
- It accounts for how many joints are swollen, tender, ESR/GH levels, and how the person is feeling
What 2 DAS28 scores indicate moderate, & severe?
MODERATE = >3.2
SEVERE = >5.1
What are the 4 Janus Kinase inhibitors (JASKi) which can be given?
- Baricitinib
- Tofacitinib
- Upadacitinib
- Filgotinib
(Remember first 2 as bari & tofa, which are given if DAS28 >3.2)
- If the patients DAS28 is >5.1, any of these options can be given
How do JAK inhibitors work?
They inhibit tyrosine kinase, so cytokine activation is inhibited & inflammation does not occur
What are the 3 bDMARDs which can be given?
When are they given?
- Etancercept
- Infliximab
- Adalimumab
They are given if the DAS28 score is >3.2 if 2nd line treatment has not worked
If a patients DAS28 score is >5.1, what drug options can you give them?
Any JAK inhibitor or bDMARD, except rituximab
What should you do if the patient is not responsing to their bDMARD/JAK inhibitor?
Either change the bDMARD, or introduce rituximab (or switch to JAK inhibitor if not using it before)
How does rituximab work?
It is a monoclonal antibody which causes lysis of B lymphocytes.
When should you use rituximab?
If the patient has not responded to previous DMARDs & 1 other tumour necrosis factor inhibitor (the 3 bDMARDS infliximab, adalimumab, or etanercept)
What change in the DAS28 score indicates a good response?
A 1.2 change
What are the 4 drugs which can be used as the final step, if the patient cannot have rituximab?
- Filgotinib (JAKi)
- Updatacitinib (JAKi)
- Sarilumab (IL-6 inhibitor)
- Tocilizumab (IL-6 inhibitor)
Which drug is only given as part of clinical trials in RA?
Anakinra (IL-1 antagonist)
THIS FLASHCARD IS JUST A SUMMARY OF ALL THE DRUGS IN ORDER OF THE STEPS TO TAKE THEM FOR RHEUMATOID ARTHRITIS.
- cMARD given - methotrexate 7.5mg weekly + 5mg folic acid (+ prednisolone 7.5mg)
- If cannot take MTX, then give either leflunomide, sulfalazine, or hydroxychloroquine
- If above unresponsive, measure DAS28 score. If it is >3.2, you can choose either:
- bDMAD: infliximab, etanercept, or adalimumab
- JAK inhibitor: filgotinib, or upadacitinib - If above unresponsive, & their DAS28 is >5.1, you can give any JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) or bDMAD
- If their DAS28 is still high, either initiate rituximab or choose another drug
- If their DAS28 is still >5.1, you HAVE to give rituximab
- If rituximab not tolerated, then any medication can be given
- if the above step does not work, you can choose from: filgotinib, upadacitinib, sarilumab, or tocilizumab
