Rheumatoid Arthritis

Question 1

Name of conventional synthetic DMARD?

Answer 1

Methotrexate

Question 2

MOA of Methotrexate?

Answer 2

Raise adenosine levels due to AICAR transformylase and ATIC inhibition (Major action)

Inhibit Dihydrofolate reductase and thymidylate synthetase (Minor action)

Overall effects:

1. Raise extracellular adenosine level and activate Adenosine A2a receptor
2. Anti-proliferative effects on T cells and inhibit macrophage functions
3. Lower pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis”

Question 3

Uses of Methotrexate?

Answer 3

First-line csDMARD

Long-term efficacy, acceptable toxicity

Associated with significantly lower mortality

Often combined with other sDMARDs for optimal effects”

Question 4

ADR of Methotrexate?

Answer 4

Methotrexate Toxicity:

1. Nausea, vomiting
2. Mouth and GI ulcers
3. Hair thinning
4. Myelosuppression - Leukopenia, hepatic fibrosis, pneumonitis”

Question 5

Give what with Methotrexate?

Answer 5

Concomitant Folic acid / Folinic acid given 12-24 hr after methotraxte to lower toxicity and minimize ADR.

• Folate is cheaper but high doses are needed as folate does not efficiently rescue toxicity.
• Folinic acid is more efficient at rescuing toxicity as Dihydrofolate Reductase is bypassed

2. Avoid giving with some antibiotics and NSAIDs

Question 6

Name of targeted synthetic DMARD?

Answer 6

Tofacitinib

Question 7

MOA of Tofacitinib?

Answer 7

Janus Kinase (JAK) pathway inhibitor

Blocks cytokine production by blocking JAK/STAT-activation of gene transcription

Question 8

Uses of Tofacitinib?

Answer 8

Combined with Methotrexate for moderate to severe RA

Monotherapy in cases of intolerance to MTX

Effective in MTX- and multiple bDMARD-refratory active RA

Approved for Psoriatic Arthritis (PsA)

Question 9

ADR of Tofacitinib?

Answer 9

Cytopenia including neutrophils, lymphocytes, platelets and NK cells

Immunosuppression - opportunistic infection esp. high risk of Herpes Zoster infection amongst Asians

Anaemia - affects JAK2 activation by erythropoietin

Hyperlipidemia - higher total, LDL and HDL Cholesterol and TG

Do not combine with biological DMARDs - risk of double immunosuppression”

Question 10

Name of biologic DMARD - TNF blocker?

Answer 10

Infliximab

Question 11

MOA of infliximab?

Answer 11

Bind TNF-alpha.

Question 12

Use of Infliximab?

Answer 12

For RA patients who do not respond well to sDMARD therapies

Used with MTX for optimal effects”

Question 13

ADR of infliximab?

Answer 13

Respiratory and skin infection

Lymphoma, optic neuritis

Exacerbation of multiple sclerosis

Leukopenia, aplastic anemia

Contraindicated for live vaccination, Hep B”

Question 14

Name of biologic DMARD - IL-1 blocker?

Answer 14

Anakinra

Question 15

Name of biologic DMARD - IL-6 blocker?

Answer 15

Tocilizumab