Rheumatoid Arthritis and Disease Modifying Agents

Question 1

Rheumatoid Arthritis: Clinical Features

Answer 1

A chronic, autoimmune, inflammatory disease:

• joint swelling
• joint tenderness
• destruction of synovial joint (WBC attack synovium)
• severe disability
• premature mortality

Question 2

Cytokines

Answer 2

TNF alpha
Interleukin-1 (IL-1)
IL-6

Question 3

Cytokines effect

Answer 3

• Increased endothelial permeability to leukocytes
• Stimulate osteoclasts
• stimulate release of collagenase
• progressive, irreversible deformities in joints and functional impairment

Question 4

Disease Modifying Anti-Rheumatic Drugs (DMARDs)

Answer 4

• Slows disease progression and preserve structure/function of joints
• inhibits cytokines
• suppresses activity of lymphocytes
• biologic and non biologic

Question 5

Adjunct Treatments

Answer 5

• NSAIDs (do not affect disease process, reduces pain and inflammation)
• Corticosteroids

Question 6

Methotrexate MOA

Answer 6

• Reduced purine biosynthesis results in reduced DNA synthesis
• at low doses (RA), selectively inhibits cytokine production and the replication of T and B cells

Question 7

Methotrexate Contraindication

Answer 7

pregnancy and breastfeeding (discontinue 3 months before conception)

Question 8

Methotrexate ADEs

Answer 8

• Decreased immune response: myelosupression
• GI toxicity: nausea & mucosal ulcers
• Pulmonary toxicity
• Hepatic fibrosis (monitor LFTs)
• Thrombocytopenia
• mild alopecia
• ADD folic acid to decrease ADEs

Question 9

Leflunomide MOA

Answer 9

Inhibits autoimmune T cell proliferation and production of autoantibodies

Question 10

Leflunomide Contraindication

Answer 10

pregnancy and breastfeeding

Question 11

Leflunomide ADEs

Answer 11

Diarrhea
Steven's Johnson Rash
Alopecia
Hematologic toxicity
Severe Hepatotoxicity

Question 12

Sulfasalazine and pregnancy

Answer 12

Pregnancy Category B

Question 13

Sulfasalazine ADEs

Answer 13

• GI effects
• Lupus like syndrome
• Headache, fever, rash
• Hepatotoxicity
• Avoid if documented sulfa allergy

Question 14

What tests do we perform for Methotrexate, Leflunomide, Sulfasalazine

Answer 14

Check CBC, LFTs, SCr

Question 15

Biologic DMARDs MOA

Answer 15

• Interfere with cytokine function, signal transduction or production
• inhibit the “second signal” required for T cell activation
• deplete B cells
• rapid onset of action

Question 16

Biological DMARDs precaution

Answer 16

• Increased risk of infection by both bacterial pathogens and atypical fungal and opportunistic pathogens
• Ensure proper vaccination history

Question 17

Tumor Necrosis Factor (TNF) inhibitors

Answer 17

Adalimumab
Certolizumab
Etanercept
Golimumab
Infliximab

Question 18

Safety in Anti TNF DMARDs

Answer 18

• Increased susceptibility to infections
• New or worsening cases of heart failure
• increased risk of lymphoma
• Injection site reactions, arthralgia, rash, cough

Question 19

Non Anti TNF: Anakinra

Answer 19

Use: less potent than TNF inhibitors-rarely used
ADE: avoid combo with other biologics- increased frequency of SAEs

Question 20

Non Anti TNF: Rituximab

Answer 20

Use: eliminates B cells
ADE: Fatal infusion related reaction

Question 21

Non Anti TNF: Abatacept

Answer 21

Use: controls “cross talk” between T cells
ADE: Avoid with anti-TNF biologics (increases risk of infections)

Question 22

Non Anti TNF: Tocilizumab

Answer 22

Use: Antibody binds to IL-6 receptors
ADE: Severe infections, GI perforations, neutropenia, thrombocytopenia, LFT elevations, hyperlipidemia

Question 23

Non Anti TNF: Sarilumab

Answer 23

Use: IL-6 antagonist

Question 24

Kinase Inhibitors MOA

Answer 24

• Inhibits the activity of JAK enzyme at cytokine receptor, which reduces cytokine transmission signaling, which decreases
• Blocks actions of multiple but NOT ALL cytokines

Question 25

Kinase Inhibitors contraindication

Answer 25

Not used with other biologic DMARDs (infection)

Often used with methotrexate

Question 26

Kinase inhibitors drugs

Answer 26

Tofacitinib

Baricitinib

Question 27

ADEs of JAK inhibitors

Answer 27

Diarrhea
Infections
Reactivation of TB
Risk of Malignancy
Avoid live vaccines
GI perforation
Hyperlipidemia
Anemia, neutropenia
Hepatotoxicity
Thrombosis