*DMARD's

Question 1

What are DMARD’s?

Answer 1

Disease Modifying Anti-Rheumatic Drugs (DMARDs)

a class of therapeutics that slow disease progression

• Arthritis, psoriasis, colitis are well recognized incurable
  chronic inflammatory auto-immune diseases
• Pain relief is not commonly provided by these drugs
• Unlike steroids and NSAIDs, they do not treat symptoms

Question 2

EXAMPLES OF CONVENTIONAL DMARDS

(disease modufying anti-rheumatic disease)

Answer 2

• Methotrexate, Pemetrexed
• Hydroxychloroquine [Plaquenil®]
• Sulfasalazine: anti-inflammatory NSAID
• Cyclosporine: T-cell inhibitor
• Azathioprine: T-cell inhibitor
• Penicillamine: Cu+ and heavy metal chelator, cystine depletor
• Cyclophosphamide: DNA alkylation and cross-linker
• Leflunomide: pyrimidine synthesis inhibitor

Question 3

Indications of methotrexate (DMARD)

Answer 3

• Various cancers: calculated
• Breast cancer
• Rheumatoid Arthritis: 7.5-25 mg PO/IM qwk
• Psoriasis: 10-25 mg PO/IM /IV qwk

Question 4

Mechanism of action of methotrexate

Answer 4

• Acts as a folic acid analogue, inhibits DHFR, thus preventing formation of FH4
• Inhibits lymphocyte proliferation
• Anti-inflammatory effects mediated by activation of
  adenosine pathways

Question 5

Adverse effects of methotrexate

Answer 5

• Common:
  
  • ​Photosensitivity, pruritus, anemia, dizziness
• Severe:
  
  • Neurotoxicity
• Black Box
  
  • Deaths reported: monitor bone marrow, liver, lung & kidneys; opportunistic infections
  • Potentially fatal myelosuppression w/ NSAIDs

Question 6

Cautions for use of methotrexate

Answer 6

Head injury

Question 7

Indications of hydroxychloroquine (DMARD)

Answer 7

• Rheumatoid Arthritis
• SLE (systemic lupus erythematosus)
• Sjögren’s Syndrome: off-label
• Malaria Prophylaxis: 400 mg PO qwk
• Malaria Tx: 800 mg PO x 1, then 400 mg PO x 1 at 6, 24, and 48h

Doses of 1kg in a lifetime places a patient at very high risk of retinopathy

Question 8

/mechanism of action of hydroxychloroquine

Answer 8

• Inhibits auto-immune disease mediators including rheumatoid factor and acute phase reactants including IL-1, IL-6, and TNF-a
• Inhibits PLA2, lymphocyte proliferation, antigen presentation, lysosomal enzyme release
• Interrupts parasitic vesicle functions and phospholipid
  metabolism by increasing pH in food vacuoles

Question 9

Adverse reactions of hydroxychloroquine (DMARD)

Answer 9

• Common:
  
  • Headache, photosensitivity
• Serious:
  
  • Hypersensitivity: angioedema
• Ocular:
  
  • retinopathy (bull,s eye maculopathy), vortex keratopathy( swirly shape of deposits on cornea)
• ​Topical Ophthalmic Drug Interactions
  
  • None
• Contraindications
  
  • Retinal or visual changes

Bull’s eye maculopathy: dose dependent - based on lifetime dosage (how much the pt has taken their whole life [cumulative])
■ 1,000 g (1 kg) = great risk for retinal toxicity

Question 10

Examples of TUMOR NECROSIS FACTOR INHIBITORS

Answer 10

• Adalimumab [Humira®]
• Infliximab [Avsola®, Inflectra®, Remicade®,Renflexis®]
• Etanercept [Enbrel®]
• Certolizumab pegol [Cimzia®]
• Golimumab [Simponi®]
• Auranofin

Question 11

Indications of ADALIMUMAB (tumor necrosis factor inhibitor)

Answer 11

• Ulcerative Colitis
• Psoriasis
• Ankylosing Spondylitis
• Crohn Disease
• Uveitis

Question 12

Mechanism of action of ADALIMUMAB (tumor necrosis factor inhibitor)

Answer 12

• Binds and inhibits tumor necrosis factor alpha (TNF-α),
• *reducing inflammation and altering immune response**

Question 13

Adverse reactions of ADALIMUMAB (tumor necrosis factor inhibitor)

Answer 13

• Common:
  
  • Headache,
  • flu-like syndrome (monoclonal antibodies - messing with our immune system),
  • HTN (suppressing TNF pathways that usually destroy tumors)
• Black Box Warnings
  
  • Opportunistic infection
  • Malignancy

Question 14

Cautions for the use of adalimumab (TNF)

Answer 14

• Opportunistic infection history
• Uncontrolled DM

Question 15

Examples of JAK INHIBITORS

Answer 15

• Tofacitinib [Xeljanz®]
• Upadacintinib [Rinvoq®]
• Baricitinib

Question 16

Indications of TOFACITINIB (JAK inhibitor)

Answer 16

• Rheumatic Arthritis
• Psoriatic arthritis
• Ulcerative colitis

Question 17

Mechanism of action of TOFACITINIB (JAK inhibitor)

Answer 17

• Inhibits janus-associated kinases (JAK) disrupting cytokine and growth factor signaling pathways

Question 18

Adverse reactions of TOFACITINIB (JAK inhibitor)

Answer 18

• Common:
  
  • Headache,
  • cholesterol increase
• Serious:
  
  • Cytopenia
  • Opportunistic infection
  • Malignancy
  • Viral reactivation

Question 19

Contraindications and cautions for the use of TOFACITINIB (JAK inhibitor)

Answer 19

• Contraindications
  
  • ​Active infection
• Cautions
  
  • Diabetes mellitus
  • Herpes Zoster history

Question 20

Example of PHOSPHODIESTERASE INHIBITORS

Answer 20

• Apremilast

Question 21

Indications of Apremilast (PHOSPHODIESTERASE INHIBITORS)

Answer 21

• Psoriatic Arthritis
• Psoriasis
• Oral ulcers, Bechet disease-associated

Question 22

Mechanism of action of APREMILAST (phosphodiesterase inhinitor)

Answer 22

• Selectively inhibits phosphodiesterase-4 (PDE-4) resulting in
  elevated intracellular cAMP levels
• NF-kB synthesis is inhibited
  
  • Anti-inflammatory cytokine production is stimulated
  • A recent study suggested that apremilast reduced symptoms
    but not disease progression in psoriatic arthritis

Question 23

Adverse reactions and cautions of Apremilast (phosphodiesterase inhibitor)

Answer 23

Adverse Reactions

• Common:
  
  • Headache,
  • migraine,
  • weight loss
• Serious:
  
  • Hypersensitivity reaction
  • Suicidal ideation
• Topical Ophthalmic Drug Interactions
  
  • None
• Cautions
  
  • Hypotension