Rheumatoid arthritis Flashcards
How does MTX cause bone marrow suppression and GI disturbances?
MTX inhibits dihydrofolate reductase (DHFR), reducing levels of tetrahydrofolate and thus synthesis of purines and pyrimidines. This inhibition leads to decrease in production of DNA, RNA & certain AAs, ultimately disrupting growth and pro-life of rapidly divings cells such as those found in bone marrow and walls of GIT.
Clinical presentation of RA
- Pain
- Swelling
- Redness and warm
4. Early morning stiffness >30 min
5. Symmetrical polyarthritis
Laboratory findings 1
Autoantibodies
- Rheumatoid factor RF +(ve)
- Anti citrullinated peptide antibodies ACPA , anti-CCP assays (+ve)
Laboratory findings 2
ESR increase
CRP increase
Laboratory findings 3
Hg decrease
Platelets increase
WBC increase
Diagnosis of RA
At least 4 of:
1. Early morning stiffness >1 hour >6 weeks
2. Swelling of >3 joints >6 weeks
4. Swelling of wrist/MCP/PIP joints >6 weeks
5. Rheumatoid nodules
6. +ve RF &/ anti-CCP tests
7. Radiographic changes
Drugs used in RA
- NSAIDs
- Glucocorticoids
- DMARDs
Drug class of MTX
csDMARDs
Drug class of Adalimumab
bDMARDs
Drug class of Tofacitinib
tsDMARDS
Drug class of Infliximab
bDMARDs
Drug class of Etanercept
bDMARDs
Drug class of Golimumab
bDMARDs
Drug class of Anakinra
bDMARDs (not available in SG)
Drug class of Rituximab
bDMARDs
Drug class of Abatacept
bDMARDs (not available in SG)
1st line treatment of RA
MTX monotherapy
Short term low-dose GC can be added when initiating
Dose of MTX
Initiation : 7.5mg once weekly
2.5-5mg/week increment every 4-12 weeks
Target: 15mg/week
What needs to be co-prescribed with MTX? Why?
Folic acid 5mg/week
Rescue therapy: Folic acid, a synthetic form of the naturally occuring vitamin B9, helps prevent MTX-induced side effects by counteracting the reduced level of tetrahydrofolate.
Dose adjustment of MTX
CrCl<50ml/min: 50%
CrCl<30ml/min: AVOID
SE/cautions of MTX
GI: N/V, diarrhoea
Increases liver transaminase
Myelosuppression
TENS/SJS
Teratigenic
Monitoring of MTX
FBC
LFT (AST, ALT, albumin, bilirubin)
SCr
MOA of sulfasalazine
Modulates leukotrienes
Inhibit TNF
CI of sulfasalazine
Sulfonamides allergies
Caution in G6PD deficiency
MOA of hydroxychloroquine
Inhibits locomotion of neutrophils, chemotaxis of eosinophils, complement-dependent antigen-antibody reactions
MOA of leflunomides
Decrease lymphocyte action
Dose adjustment of leflunomides
ALT>2x ULN: AVOID
CI of hydroxychloroquine
Pre-existing retinopathy
G^PD deficiency
Caution for leflunomides
Very long half life
Requires wash out by cholestyramine
Teratogenic
On MTX, but not at target
Add bDMARD/tsDMARD
With bDMARDs/tsDMARDs, not at target
Switch to bDMARD or tsDMARD of different class
MOA of bDMARD
Binds to cytokines or their receptors to down regulate or inhibit their functions, which reduces immune and inflammatory responses
MOA of tsDMARD
Binds to JAK proteins inside cells to prevent JAKs from transphosphorylating the associated cytokine and growth factor receptor
DMARDs with TNF-alpha target
- Adalimumab
- Etanercept
- Golimumab
- Infliximab
DMARDs with IL-1 target
Anakinra
DMARDs with IL-6 target
Tocilizumab
DMARDs with CD20 target
Rituximab
DMARDs with CD28 target
Abatacept
Initiating DMARDs
- Pre-treatment screening
- TB
- Hepatitis B&C - Vaccination
- Pneumococcal
- Influenza
- Hepatitis B
- Varicella zoster - Laboratory screening
- FBC
- LFT
- Lipid panel
- SCr
Safety concerns of bDMARDs/tsDMARDs 1
Injection site/infusion reaction
Safety concerns of bDMARDs/tsDMARDs 2
Myelosuppression
- Monitor FBC with WBC differentials & platelet count
Safety concerns of bDMARDs/tsDMARDs 3
Infections
- URTI, TB, opportunistic infections
Safety concerns of bDMARDs/tsDMARDs 4
Malignancy risk
Safety concerns of bDMARDs/tsDMARDs 5
Autoimmune diseases
Safety concerns of bDMARDs/tsDMARDs 6
CVD
- HF (Avoid TNF-a inhibitors in NYHA class III & IV), HTN
Safety concerns of bDMARDs/tsDMARDs 7
Hepatic
- Monitor LFT
Safety concerns of bDMARDs/tsDMARDs 8
Metabolic effects
- Hyperlipidemia: monitor lipid panel
Safety concerns of bDMARDs/tsDMARDs 9
Pulmonary diseases
Safety concerns of bDMARDs/tsDMARDs 10
GI perforation
- Especially IL-6 & JAK inhibitors
Safety concerns of bDMARDs/tsDMARDs 11
Thrombosis
- Especially IL-6 & JAK inhibitors