Treatment of RMDs Flashcards
Describe the initial treatment plan for RA with MILD disease activity at initial presentation: not pregnant or planning pregnancy
1st Line: conventional DMARD:
- hydroxychloroquine - it is better tolerated and has a more favourable risk profile than other DMARDs
Consider: Corticosteroid
- Prednisolone
Consider: non-steroidal anti-inflammatory drug (NSAID)
- ibuprofen
NB: hydroxychloroquine: should only be considered for initial therapy if mild
BMJBP
Describe the initial treatment plan for RA with MODERATE-SEVERE disease activity at initial presentation not pregnant or planning pregnancy
1st line cDMARD:
- methotrexate (primary option) with folic acid supplementation
- sulfasalazine (secondary option)
- hydroxychloroquine (secondary option)
- leflunomide (secondary option)
- bridged with corticosteroid - prednisolone for 2/3 months until methotrexate starts working
2nd line: Combination treatment with multiple cDMARDs
3rd line: bDMARDs
- etanercept (primary option)
- infliximab
- adalimumab
4th line: Rituximab
Double check with lecture
TOM TIP: The main biologics to remember are [3] (TNF inhibitors), and [1] (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).
TOM TIP: The main biologics to remember are adalimumab, infliximab and etanercept (TNF inhibitors), and rituximab (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).
They cause immunosuppression, increasing the risk of infection, certain cancers (e.g., skin) and reactivation of latent TB.
Describe the dosing regimen for methotrexate [1]
Methotrexate interferes with folate metabolism and suppresses the immune system. It is given once a week
Folic acid 5mg is taken once a week (on a different day to the methotrexate)
Describe the MoA of Leflunomide [1]
Name 5 side effects [5]
Leflunomide is an immunosuppressant medication that interferes with the production of pyrimidine.
Side effects:
* Mouth ulcers and mucositis
* Increased blood pressure
* Liver toxicity
* Bone marrow suppression and leukopenia (low white blood cells)
* Teratogenic (harmful to pregnancy) and needs to be avoided before conception in both women and men
* Peripheral neuropathy
TOM TIP: The unique side effects worth remembering are:
- Methotrexate [3]
- Leflunomide [2]
- Sulfasalazine [3]
TOM TIP: The unique side effects worth remembering are:
Methotrexate:
* Bone marrow suppression
* leukopenia
* highly teratogenic
Leflunomide:
- Hypertension
- peripheral neuropathy
Sulfasalazine:
- Orange urine
- male infertility (reduces sperm count)
TOM TIP: The unique side effects worth remembering are:
- Hydroxychloroquine [3]
- Anti-TNF medications [2]
- Rituximab [2]
Hydroxychloroquine:
- Retinal toxicity
- blue-grey skin pigmentation
- hair bleaching
Anti-TNF medications:
- Reactivation of tuberculosis
Rituximab:
- Night sweats
- thrombocytopenia
[2] are considered the safest DMARDs in pregnancy
Hydroxychloroquine and sulfasalazine are considered the safest DMARDs in pregnancy
Which RA medication has a risk of reactivating TB? [1]
Etanercept and also
adalimumab, infliximab, golimumab and certolizumab
Which RA medication has a risk of an infusion reaction? [1]
Rituximab
How do you treat a flare of RA? [1]
flares of RA are often managed with corticosteroids - oral or intramuscular
- methylprednisolone
What needs to be checked before starting DMARDs?
Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFTs need to be checked before starting DMARDs.
State 5 side effects of corticosteroids
Osteoporosis; weight gain; DM; HTN
Methotrexate:
1. MoA?
2. Advantages [3]
3. Disadvantages [6]
MoA:
- Folic acid inhibitor (due to inhibition of dihydrofolate reductase) which stops cell proliferation; impacts rapidly dividing cells
Advantages:
- Inexpensive
- Oral or injection
- Well established safety profile
Disadvantages
- N&V
- Mouth sores
- Hair loss
- Liver toxicity
- Bone marrow suppresion
- Lung toxicity
What do you screen for prior to starting methotrexate; SSZ and LEF tx? [3]
- FBC; UEs; LFTs
- Viral serology screen
- Baseline CXR - for MTX as can cause PF
- Baseline BP for LEF
How do you manage / monitor ongoing methotrexate; SSZ and LEF prescription? [3]
FBC and LFTs are to be monitored every 2 weeks for the
first 6 weeks (induction phase) and with any increased
dose, and then monthly for 3 months.
3-monthly monitoring for MTX, SSZ, and LEF includes..? [5]
3 monthly FBC; ALT; AST; ALP; Albumin; U&Es
What important AE do you need to monitor for with hydroxychloroquine tx? [1]
Retinal toxicity - requires regular eye exams
Also: gastrointestinal upset, skin rash
Describe the MoA [1] and AEs [3] of MMF
MoA:
- Inhibits enzyme used for de novo purine synthesis - effects T & B cells
AEs:
- GI upset
- Infections
- Bone marrow suppression
What should you offer women prior to cyclophosphamide treatment? [1]
Egg harvesting treatment as causes infertility
Describe the MoA and side effects of cyclophosphamide
MoA:
- Alkylating agent - cross links DNA strands, leading to cell death
Effects:
- Bone marrow suppression
- Bladder inflammation - hamorrhagic cystitis
- Infertility
- N&V
Describe some of the unwanted effects of blocking TNFa
TNFa is essential for granuloma formation, organisation and maintenance - risk of TB reactivation AND increased risk of infection
Autoimmune reactions:
- paradoxical psoriasis (new onset or worsening)
- drug induced lupus
- MS or optic neuritis
Allergic reactions
HF exacerbations
Blood abnormalities (anaemia; neutropenia)
Liver toxicity
Increased risk of malignancies
What should you screen for prior to anti-TNF tx? [4]
FBC ++
Serology for HIV, HBV & HCV
CXR and TB Elispot
Exclude infections, pregnancy, malignancy, NYHA Class III/IV and EF < 50%
antibodies to antibodies
Can produce antibodies agaisnt
Name an anti-TNF that can be used in pregnancy [1]
Certolizumab
Name an anti-TNF that might cause less chance of infection [1]
Etanercept
Whats an overall JAK inhibitor MoA? [1]
JAKs are inside the cells (block the messages delivered by cytokines inside the cells)
There are different JAKs
Name an advantage of JAK inhibitors tx [1]
Can be taken orally (c.f. biologics are often infusions)
Name some side effects of JAK inhibitors [4]
Increased risk of serious infections - use in caution with > 65
Risk of MACE - caution with CVD
Malignancy - particularly increased risk of lymphoma and lunger cancer
Thrombotic events; GI side effects and anaemia
Describe the treatment pathway for RA
Which alternative drug should be used if pregnant or pregnancy planning? [1]
Sulfasalazine
How often do you perform blood tests for methotrexate monitoring? [1]
How do you assess response to methotrexate use? [1]
Assess using DAS28 = disease activity score of 28 joints
