RA

Question 1

PHARMACOLOGIC TREATMENT

(5)

Answer 1

• NSAIDs
• corticosteroids
• DMARDs
• Biologic: anti-TNF
• Biologic: non-TNF

Question 2

NSAIDs

• Effective in reducing pain, swelling, and stiffness
• Do NOT alter disease ___
• Dose at anti-inflammatory doses
• Use in combination with ___

Answer 2

• progression
• DMARDs

Question 3

CORTICOSTEROIDS

• Used for anti-inflammatory & ___ properties
• Not used as ___
• Use in combination with DMARD
• Use in ___ flares
• Use in patients with extra-articular manifestations

Answer 3

• immunosuppressive
• monotherapy
• cute

Question 4

CORTICOSTEROIDS: DOSING

• ___ and ___ have steroid sparing effects
  ■ Low dose: < 10mg/day of prednisone
  ■ High dose: > 10mg/day up to 60mg daily
  ■ Short-term: < ___ months of therapy

Intraarticular injections
o Do NOT use > every __ - __ months
o Use 10 – 25 mg/injection of HC per joint

Answer 4

• NSAIDs, DMARDs
• 3
• 2-3

Question 5

CORTICOSTEROID ADVERSE EFFECTS

Short Term
- ___ glycemia
- gastritis
- ___ changes
- elevated ___

Long Term
- ___ necrosis
- cataracts
- ___
- growth failure
- ___

Answer 5

• hyperglycemia
• mood
• BP
• aseptic
• obesity
• osteoporosis

Question 6

DMARDs

Disease Modifying Anti-Rheumatic Drugs
- Potential to decrease/ ___ joint damage & ___ joint integrity
- ___ of initiation is critical
- Onset of action is ___

Answer 6

• prevent, preserve
• timing
• delayed

Question 7

Conventional Synthetic DMARDs

(4)

Answer 7

• Methotrexate (MTX)
• Sulfasalazine (SSZ)
• Hydroxychloroquine (HCQ)
• Leflunomide

Question 8

METHOTREXATE

• Most predictable benefit
• DMARD of ___
• DMARD with best ___ outcome
• MOA: inhibit ___ acid reductase (inhibits neutrophil adhesion and chemotaxis)

Answer 8

• choice
• long-term
• dihydrofolic

Question 9

METHOTREXATE

Dosing Regimen
■ 2.5 mg tablets
■ Dose: ___ mg per ___ by mouth or intramuscularly (up to 15-20 mg – weekly dose can be taken in one day)
■ Onset: __ - __ months

Pharmacokinetics
■ 35- 50% bound to ___
■ Hepatic metabolism with some renal excretion

Answer 9

• 7.5, week
• 1-2
• albumin

Question 10

MTX: ADVERSE EFFECTS

Hematologic
- Bone ___ suppression

Gastrointestinal
- N/V/D*
- Stomatitis/mucositis

Hepatic
- Cirrhosis
- Hepatitis
- Fibrosis
* = prescribe 1mg/day of ___ acid to reduce symptoms

Pulmonary
- Pneumonitis
- Fibrosis

Dermatologic
- Rash
- Urticaria
- Alopecia

Teratogenic
– Wait one cycle on BCP
– Wait __ months before considering conception

Answer 10

• marrow
• folic
• 3

Question 11

MTX: CONTRAINDICATIONS

• pregnancy
• chronic ___ disease ( ___ abuse)
• immunodeficienncy
• Pre-existing blood dyscrasias
• Pleural/peritoneal effusions
• Leukopenia/ ___
• CrCL < ___ ml/min

Answer 11

• liver, EtOH
• thrombocytopenia
• 40

Question 12

MTX: MONITORING

baseline:
- ___
- CBC
- ___
- ___
- albumin

maintenance: CBC, SCr, LFT
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- > 6 months: 12 weeks

Answer 12

• CXR
• SCr
• LFTs

Question 13

LEFLUNOMIDE (Arava®)

Prodrug
■ MOA:
– inhibit de novo biosynthesis of ___
– Interferes with ___ kinase activity
– Inhibit cell cycle progression

Answer 13

• pyrimidines
• tyrosine

Question 14

LEFLUNOMIDE (Arava®)

Dosage Regimen
■ 10 mg and 20 mg tablets
■ Dose: ___ mg by mouth x 3 days; then 20 mg daily
■ Onset: 1 month
■ Caution: if also taking MTX b/c ___ toxicity

Pharmacokinetics
■ t ½ = 14 – 16 ___
■ ___ clearance

Answer 14

• 100
• liver
• daysLEFLUNOMIDE (LEF):
  ADVERSE EFFECTS
• Hepatobiliary

Question 15

LEFLUNOMIDE (LEF): ADVERSE EFFECTS

• Diarrhea
• Rash
• Alopecia
• Increased ___
• ___

Answer 15

• LFTs
• Teratogenicity

Question 16

LEF: MONITORING

___ , ___ , and ___

Baseline

Maintenance
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- >6 months: 12 weeks

Answer 16

CBC, SCr, LFT

Question 17

SULFASALAZINE

Prodrug: cleaved in colon to ___ and ___
■ MOA: inhibits ___

Dosing Regimen:
– 500 mg tablets
– Dose: 500mg by mouth twice daily
– 1g 2-3 times daily
– Onset: 1-2 months

Answer 17

• sulfpyradine, 5-ASA
• IL-1

Question 18

SSZ: ADVERSE EFFECTS

Gastrointestinal
- N/V/D, anorexia

Dermatologic
- ___ / Urticaria/ Photosensitivity

Hematologic
- Leukopenia, ___
- Rare: Hemolytic and aplastic anemia

Caution for ___

Answer 18

• Rash
• thrombocytopenia
• allergy

Question 19

SSZ: MONITORING

___ , ___ , and ___

Baseline
Maintenance
- < 3 months: 2-4 weeks
- 3-6 months: 8-12 weeks
- >6 months: 12 weeks

Answer 19

CBC, SCr, LFT

Question 20

HYDROXYCHLOROQUINE

MOA: modification of ___ infiltration in joint

Dosing Regimen
– 200 mg tablets
– Dose: 200 mg by mouth twice daily
– Onset: 2-4 months (D/C if not efficacious in ___ months)

Pharmacokinetics
– ___ metabolism
– ___ excretion

Answer 20

• cytokine
• 6
• hepatic
• renal

Question 21

HCQ: ADVERSE EFFECTS

Advantage
- No ___, hepatic, renal toxicities

Ocular
- ___ toxicity
- > 70 yo, cumulative dose > 800 g, night/peripheral
changes

Gastrointestinal
– N/V/D (take with ___ )

Dermatologic
– Increase skin ___ , rash, alopecia

monitoring: ___ exam every 6-12 months

Answer 21

• myelosuppression
• retinal
• food
• pigment
• vision

Question 22

TNF NEUTRALIZERS (5)

Answer 22

• Etanercept
• Infliximab
• Adalimumab
• Golimumab
• Certolizumab

Question 23

TNF NEUTRALIZERS: WARNINGS/PRECAUTIONS

Risk of ___

Do not use in combination with ___ inhibitors or ___ co-stimulation modulators

Black Box warnings
■ Neurologic / ___ disorders
■ Malignancies
■ Congestive heart failure
■ ___ reactivation
■ No concurrent ___ vaccination administration

Answer 23

• infection
• IL-1, t-cell
• demyelinating
• Hepatitis B
• live

Question 24

TNF NEUTRALIZERS: ADVERSE EFFECTS

• ___ and rash
• Risk of ___ (upper respiratory most common)
• ___ site reaction
• Exacerbations of ___
• Risk of ___
• Risk of evidence of ___ disease

Answer 24

• HA
• infection
• injection
• CHF
• malignancy
• demyelinating

Question 25

# ETANERCEPT (Enbrel®) Mechanism of Action – ___ protein with two soluble TNF receptors fused to the IgG1 molecule – Binds to and inhibits ___ – Binding occurs before the ___ can interact with cell-surface TNF receptors that would produce an inflammatory response Dosage Regimen – 50mg ___ once weekly

Answer 25

- dimeric - TNF - cytokine - SC

Question 26

# INFLIXIMAB (Remicade®) Mechanism of Action - ___ antibody - Immunoglobulin - Mouse & human portions to reduce ___ potential Dosage regimen - 3 mg/kg IV at 0,2,& 6 weeks then every 8 weeks - Can increase dose to 10mg/kg or as often as every 4 weeks - Indicated in combination with ___

Answer 26

- chimaric - antigenic - MTX

Question 27

# ADALIMUMAB (Humira®) Mechanism of Action - Recombinant ___ IgG1 monoclonal antibody specific for human ___ - Binds to ___ and blocks interaction with the p55 and p75 cell surface TNF receptors Indications - Patients who have inadequate response to one or more ___ - Can be used ___ OR in ___ Dosage Regimen ■ 40mg SC every ___ week ■ If not taking ___ can increase to 40mg SC every week for improved response

Answer 27

- human, TNF - TNF-a - DMARDs - alone, combination - other - MTX

Question 28

# GOLIMUMAB (Simponi®) Indications - Moderate to severe RA - Used in combination with ___ Mechanism of Action - ___ monoclonal antibody specific for ___ - Prevents binding of TNF-alpha to receptors Dosage Regimen - 50mg SC once ___ Monitoring Parameters: - CBC with PLT - ____

Answer 28

- MTX - human, TNF-a - monthly - LFTs

Question 29

# CERTOLIZUMAB (Cimzia®) Mechanism of Action - Binds to membrane associate and soluble ___ and neutralizes Indications - RA patients with moderate to severe disease - Can be used ___ or in ___ with non-BRM DMARDs Dosage Regimen - 400mg (2 injections of 200mg) SC at 0,2,4 weeks then 200mg every 2 weeks or 400mg every 4 weeks

Answer 29

- TNF-a - alone, combo

Question 30

# ANAKINRA (Kineret®) Indication: - Moderate to severe RA in patients who have failed one or more ___ - Can use ___ or in ___ Mechanism of Action: - ___ , non- ___ version of the human ___ receptor antagonist - Selectivity blocks IL-1 by binding to the IL-1 receptor

Answer 30

- DMARDs - alone, combo - recombinant, non-glycosylated, IL-1

Question 31

# ANAKINRA (Kineret®) Dosage Regimen ■ 100mg SC daily ■ If CrCl < ___ mL/min, use 100mg SC every ___ day ■ Do not use in ___ with TNF agents or ___ (due to increased risk of ___ ) Adverse Effects ■ ___ site reactions ■ Headache, N/V, flu-like symptoms ■ ___ to e.coli-derived proteins ■ Increased risk of serious ___ ■ Decreased ___

Answer 31

- 30, other - combo, abatacept, infection - injection - hypersensitivity - infectons - neutrophils

Question 32

# ANAKINRA: MONITORING ___ count - Prior to start - Monthly for 3 months - ___ for up to one year

Answer 32

- neutrophil - Quarterly

Question 33

# SELECTIVE T-CELL CO-STIMULATION MODULATOR ___ (Orencia®) Indication: - Moderate to severe RA - If had inadequate response to one or more __ - Monotherapy or in combination with ___ (not with TNF –inhibitors or IL-1 antagonists) Mechanism of Action: - Selective ___ modulator - Inhibits ___ activation

Answer 33

- Abatacept - DMARDs - DMARDs - co-stimulation - T-cell

Question 34

# ABATACEPT: DOSING Available in ___ mg vials - < 60kg: 500mg IV over 30 minutes - 60-100 kg: 750mg IV over 30 minutes - >100 kg: 1g IV over 30 minutes - Dose at 0, 2, and 4 weeks then every ___ weeks thereafter

Answer 34

- 250 mg - 4

Question 35

# ABATACEPT: WARNINGS - Do not use with ___ antagonists or ___ antagonists - Increased risk of ___ - No ___ vaccination administration - Caution in patients with ___

Answer 35

- TNF-a, IL-1 - infection - live - COPD

Question 36

# ABATACEPT: ADVERSE EFFECTS - Headache - Nausea - Upper respiratory ___ - Nasopharingitis - ___ reactions - Serious ___ - ___

Answer 36

- infection - infusion - infection - Malignancy