Module 1.1.2 (Pharmacotherapeutic Management of Rheumatoid Arthritis) Flashcards
What are the symptoms of rheumatoid arthritis?
- malaise, fatigue (+/- diffuse musculoskeletal pain)
- symmetrical pattern of joint pain, stiffness, swelling, and redness
- involvement of metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints and metatarsophalangeal joints (MTP)
- rare involvement of DIP joints
- morning stiffness
- weight loss, fever, depression
- and other extra-articular symptoms
What are the laboratory findings associated with rheumatoid arthritis?
- Increased ESR
- Increased C-reactive protein (CRP)
- Presence of RF (detected in later stages)
- HLA typing (genetic markers)
- Antinuclear antibodies (ANA), antibody to cyclic citrullinated peptide (CCP)
CCP = 96% specificy for RA and present before development of symptoms
- Normocytic/microcytic, normochromic anaemia
> Low serum iron, normal-to-low TIBC, normal-to-high ferritin
- Changes in joint radiographs
What are the features of RA? Provide at least FIVE.
see attached image
What is the likely course for RA (prognosis)? When are mortality rates higher?
Most patients experience temporary or permanent disability decreased QoL)
- Mortality rates 2-3X higher in the presence of extra-articular manifestations*
> Infection, cardiovascular disease
> Risk factors include those with high disease activity
*extra-articular = outside of a joint
What are some of the treatment goals for RA?
Main objective = REMISSION
> symptomatic relief + normalisation of inflammatory markers + absence of joint swelling
- Maintain joint and muscle function
- Minimize side effects of treatment
- Return to a desirable and productive life
- Reduce onset of co-morbidities e.g. depression
- Prevent complications to the heart, lungs, and other organs
What are some non-drug intervention for RA?
- Physiotherapy, exercise
- Diet (Meditteranean diet)
- OT- appliances and devices
- Smoking cessation
- Immunization
- Omega-3 fatty acid supplement i.e. fish oil (2.7g daily)
- Gamma-linolenic acid (GLA) i.e. evening primrose oil (0.5 gup to 2.8 g GLA daily)
What is the role of fish oil in RA? What are its benefits? What dose should be given?
Studies suggest about 2-3g/day of isolated DHA/EPA to reduce inflammation associated with RA (i.e. more than 2- 3 capsules daily)
> EPA inhibits the formation of AA and competes for cox enzymes which decrease the production of PGE2
Benefits include a reduction in
- joint pain
- duration of morning stiffness
- fatigue time
- number of tender or swollen joints
- use of painkillers
What are the FOUR main drug classes use to treat RA?
- Analgesics: NSAIDs, paracetamol
- Corticosteroids: systemic and intra-articular
- Synthetic Disease Modifying AntiRheumatic Drugs (sDMARDs)
- Biological DMARDs (bDMARDs)
For NSAIDs;
A) What is it specifically used to treat?
B) How to choose between cox-2 selective vs non-selective COX inhibitors?
C) What are some side effects?
D) What dose should be given for how long?
E) Can it be used with paracetamol? What should it be avoided with?
F) Who is PPI prophylaxis recommended for?
G) When should they be used? What cautions are necessary?
H) Examples of cox-2 selective vs non-selective cox inhibitors
A)
- Treat acute synovitis in all stages of RA
- Reduce inflammation, joint swelling and stiffness
B)
- Choice depends on risk vs benefit, age, renal function, comorbidity
C)
- GI, renal, CVD adverse effects
D)
- The lowest effective dose for the shortest time period
E)
- Can be used with paracetamol
- Avoid combining with anticoagulant and corticosteroid
F)
- PPI prophylaxis recommended for RA patients aged >65 and those with a past history of peptic ulcer disease
G)
- Using conventional NSAIDs or COX-2 inhibitors for reducing pain and stiffness in the short term treatment of RA where simple analgesia and omega-3 fatty acids are ineffective
- Caution is particularly required in those at risk, such as the elderly or patients who have gastrointestinal, renal or cardiovascular outcomes
H)
Cox-2 selective:
Celecoxib
Etoricoxib
Meloxicam
Parecoxib
Non-selective Cox inhibitors
Aspirin (analgesic)
Diclofenac
Ibuprofen
Indometacin
Ketoprofen
Ketorolac
Mefenamic acid
Naproxen
Piroxicam (highest risk of GI adverse effects)
For Corticosteroids;
A) What is it indicated for?
B) There are IM forms that have an effect for up to 8 weeks and IV corticosteroid which is used for disease flare. What are the properties of intraarticular injections with methylprednisolone acetate 120mg?
C) What is an example of oral corticosteroids?
D) What are some advantages?
E) What are some disadvantages?
A)
- Symptoms control while waiting for synthetic DMARDs to be effective –”Bridge therapy”
- Patients with disease “flare”
B)
- prolonged effect up to 8 weeks
- not repeated in the same joint more than 4 times a year
- injection followed by 24-48 hours splint and bed rest
- risks: infection, osteonecrosis, tendon rupture
C)
- Prednisolone 5-15mg daily orally
- Used at the lowest possible dose and for the shortest possible duration
- Taper dose slowly when ceasing therapy if doses are >7.5mg daily or tx duration of >3 weeks
D)
- Dramatically reduce pain and swelling
- Decrease disease progression
- Increase patient well-being
E)
- Efficacy reduced with dose reduction
- Undesirable side effects with long term use
For Synthetic DMARDs;
A) How do they work? What is their onset of action?A
B) When are they introduced and what is their aim?
A)
Reduce synovial inflammation and prevent joint damage
- Slow, variable onset of action
- Variable: 6 to 12 weeks
- Response to monotherapy often suboptimal; combination therapy preferred
B)
Introduced at time of diagnosis
- Aim: quick eradication of inflammation
- Efficacy greatest early in the disease course as significant joint destruction occurs in first 2 years
What are some properties of sulfasalazine (syntheticDMARD)? Include dose and adverse effects.
- 1st line in mild disease
- Dose: 500mg daily increasing up to 1.5g bd
- 4-12 weeks for onset
- Exclude G6PD deficiency or sulfonamide allergy
- GI adverse effects (minimised by EC tablet), blood dyscrasias
- Monitor FBP, CrCl, LFTs
What are some properties of hydroxychloroquine (syntheticDMARD)? Include dose and adverse effects.
- 1st line in mild disease (less effective but least toxic)
- Primarily used in combination with other DMARDs
- Dose: 200 to 400 mg daily
- Onset: 2-6 months
- Exclude G6PD deficiency
- Risk of retinopathy (ANNUAL ophthalmology review) and worsening psoriasis
- Monitor FBP, CrCl, LFTs
For Methotrexate (syntheticDMARD);
A) Why is it the gold standard for moderate to severe RA?
B) It can be used alone or in combination, what is it combined with?
C) Dose?
D) Adverse effects, how to limit this?
E) How is the co-administration of folic acid done?
F) What are the drug interactions?
G) What are some counselling points?
H) What to monitor?
A)
- proven to slow radiographic progression of the disease
- Relatively quick onset of action (4-6 weeks)
B)
- MTX + hydroxycholoroquine or sulfasalazine or leflunomide
- MTX + biological DMARDs
C)
- 10 to 25mg WEEKLY (oral)
D)
Myelosuppression, GI toxicity, pulmonary toxicity, hepatotoxicity, rash, photosensitivity
> Adverse effects can be limited by administering the methotrexate dose at night OR splitting the weekly dose over 2 consecutive days
E)
- 5 to 10mg weekly as a single dose on a different day to when methotrexate is taken – at least 24 hours after methotrexate dose
F)
- Interaction between NSAIDs and MTX is only clinically significant with high dose methotrexate (10-25mg weekly is still safe)
G)
- Avoid sun exposure
- See a doctor if coughing or difficulty breathing
- Phototoxicity
H)
- Monitor FBP, CrCL, LFTs, CXR
What are some properties of leflunomide (syntheticDMARD)? Include dose and adverse effects.
- Reserved for patient where methotrexate is not suitable
- Onset usually approx. 4 weeks
- Dose: 10 to 20 mg daily
- Transient elevation of ALT and AST
- A/Es: GI, alopecia, dyspnoea, pneumonia, hypertension, blood dyscrasias, skin reaction
- Monitor FBP, CrCl, LFTs, BP
What are the factors affecting the treatment algorithm? Provide a treatment algorithm.
- Disease severity
- Prognosis
- Patient factors
> Age
> Childbearing status
> Comorbidities
