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PHAR 255 Exam 2 > Rheumatoid Arthritis > Flashcards

Rheumatoid Arthritis Flashcards

1
Q

Compare RA and osteoarthritis.
Age
Speed of onset
Joint Sx
Affected Joints
Suration of Morning Stiffness
Presenece of systemic sx

A

Symmetrical joint pain and stiffness >6 weeks

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1
Q

What are the goals of tx for RA?

A

Prevent and control joint damage
Prevent loss of function
Maintain QoL
Decrease pain

ACHIEVE REMISSION OR LOW DX ACTIVITY

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2
Q

How can remission or low disease activity be defined in RA?

A

Tender/swollen joint count <1

A measure of function based on the Health Assessment Questionnaire (HAQ)

CRP score <1

A physician global assessment <2

A patient assessment of global disease activity (PtGA) <2 – considering how much it effects there QOL

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3
Q

General Principles of RA Management

A

1) Early recognition and diagnosis
Significant damage occurs in first two years of disease

2) Early use of DMARDs
Start within 3m of diagnosis
Depending on severity, treat aggressively

3) Concept of “tight control”
Treat until remission or low disease activity
Quickly treat exacerbations
Aggressively add DMARDs or early switch
Adjunct NSAID / steroids
Frequent reassessment

4) Responsible NSAID and glucocorticoid use
Reduce / discontinue as disease enters remission

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4
Q

What are some non-pharamcologic therapy for RA?

A

Patient education

Rest important, but balance with activity

Reduce joint stress with RA friendly tools

Occupational and physical therapy

Diet / weight loss

Surgery

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5
Q

TX Classes for RA

A
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6
Q

Use of DMARDS (traditional)

A

Slow onset of action
Controls symptoms
May delay or stop progression of disease
Requires regular monitoring

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7
Q

What is a major downfall of DMARDS? How can this be overcome to prevent damage?

A

Slow onset of action

Offer Bridging Therapy

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8
Q

What are some examples of traditional DMARDS?

A

Hydroxychloroquine
Sulfasalazine
Methotrexate
Leflunomide

Others: D-penicillamine, gold, azathioprine, cyclosporine, minocycline

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9
Q

MOA of Hydroxyxhloroquine

A

Inhibits neutrophils and chemotaxis; impairs complement system

(down stream effects of inflammatory response)

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10
Q

MOA of Sufazaline

A

Prodrug metabolized into 5-ASA and sulfapyridine

Modulates mediators of inflammatory response; may inhibit TNF

Immune system

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11
Q

Methotrexate MOA

A

Anti-folate –> less DNA synthesis, repair, cellular replication and immune response

Often supplement with folic acid

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12
Q

Leflunomid MOA

A

Inhibits pyrimidine synthesis, leading to anti-inflammatory effects

Modulates many signaling pathways

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13
Q

Which DMARD’s are considered immunosupressant? Why is this a concern? Recommendation?

A

Issues with immune suppression, infx rate increase and vaccine – worry with methotrexate and leflunomide as immunosuppressant

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14
Q

When is methotrexate considered immunosuppressive?

A

Methotrexate only considered immunosuppressant when at higher doses (25 mg)

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15
Q

Onset of DMARDS

A

Hydroxychloroquine – 2-6 months

Sulfasalazine - 2-3 months

Methotrexate – 1-2 months

Leflunomide – 1-3 months

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16
Q

Methotrexate DOSE

A

Methotrexate – 7.5 to 25mg PO weekly

Titrate to target in most cases

Renal dosing: eGFR 10 – 50ml

May initiate at target dose in select patients

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17
Q

Methotrexate Minimal Target? Is it advanategous to go beyond top target dose?

A

Minimum Target Dose: 15 mg per week – better outcomes at 25 mg per week – dose ceiling effect beyond 25

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18
Q

Methotrexate Dosage Forms. Issues/Benefits?

A

IM or Sub-cut is an option – oral – more adherence, conveince

Su-cut – slightly more potent (small increase in efficacy), less nausea, vomiting, diarhhea

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19
Q

Who can be started at a high target dose of methotrexate? Advantage?

A

Select – start right at dose – no comorbidities and accepting of potential s/e
Advantage; faster onst and start slowing dx faster

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20
Q

Titration of methotrexate? Dialysis?

A

Titration:

Average: 7.5 mg per week and increase by 2.5-5 Q 1 month

Can be used in dialysis – reduce all the numbers by 50% (including titration)

CrCl 10-50 mL/min: reduce dose 50% (including titration)

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21
Q

S/e of Hydroxychloroquine

A

Best tolerated of the DMARDs
NVD, stomach cramps
Skin / allergic lesions (10%)
Headaches, dizziness

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22
Q

S/e Sufazaline

A

Headache
Photosensitivity
NVD

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23
Q

S/E Leflunoamide

A

Nausea/diarrhea – 60% of pts d/c because of this
Rash and hypertension
Reversible alopecia

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24
Q

Common S/e of Methotrexate

A

Nausea / vomiting*
Fatigue*
Stomatitis*
Photosensitivity
Hair loss
Skin itch / burning / rash

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25
Q

Strategies to manage methotrexate side effects? What side effects?

A

Only works on the side effects:
Nausea / vomiting*
Fatigue*
Stomatitis*

No counteraction between folic acid on same day as methotrexate – does not reduce how well methotrexate works

25 mg per week – need to take in same day – 12.5 mg in morning and 12.5 mg at night

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26
Q

Serious Side Effects of Hydroxychloroquine

A

Myopathy

Ocular toxicity – metabolites deposit n eye, long time (1000 mg cumulative dose) – baseline then every year

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27
Q

Serious Side Effects of Sufalazaline

A

Hematologic abnormalities – RBC, platelet decrease

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28
Q

Serious Side Effects of Methotrexate

A

Hepatotoxicity
Hematologic abnormalities
Pulmonary toxicity
Reversible sterility in men
Infection increase – URTI’s, more serious is pneumonia

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29
Q

Serious Side Effects of Leflunomaide

A

Hepatotoxicity
Significant weight loss
Infection increase

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30
Q

Methotrexate Monitoring

A

CBC

Liver panel (LFT’s) baseline and yearly

SCr

Baseline –> Q2-4wks for first 3 months, then q3 months (draw labs 1-2d before next dose)

Chest X-ray (baseline)

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31
Q

Hydroxychloroquine C.I.

A

Pre-existing retinopathy

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32
Q

Sufazaline C.I.

A

Hypersensitivity to salicylates or sulfonamides

Asthma attacks precipitated by ASA or NSAIDs

Severe renal / hepatic impairment

Existing gastric or duodenal ulcer

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33
Q

Methotrexate C.I. and Cuations

A

Precaution/caution in lung dysfunction

C.I.:

Severe hepatic impairment

Current hematologic abnormalities

Pregnancy / breastfeeding

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34
Q

C.I. of Leflunomide

A

Moderate-severe renal (<60ml/min) / hepatic impairment

Current hematologic abnormalities or serious infection

Pregnancy / breastfeeding

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35
Q

Hydroxychloroquine D.I.
What can it cause and what drugs would be cautioned?

A

No CYP interactions
High risk QT-prolongation

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36
Q

Sulfasalazine D.I.

A

Additive nausea if used with MTX

Possible issue with Warfarin (↑ or ↓ INR)

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37
Q

Lefluomide D.I.

A

Bile-acid sequestrants cause rapid elimination – e.g. cholestyramine – can give to increase elimination

Additive immunosuppression – can combine with other immunosuppressant

Live vaccines

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38
Q

Drug Interactions of Methotrexate

A

Many drug interactions only significant based on cancer doses (e.g. 500 - 2000mg weekly)

NSAIDs
Decreases clearance of MTX, increased toxicity potential

MTX <15mg/week – likely no risk
MTX 15-25mg/week – very low risk
Risk increases with concomitant renal dysfunction

Trimethoprim (mono agent or in combination with sulfamethoxazole)
Significantly increases risk of pancytopenia at any MTX dose, consider contraindicated

PPIs
Only an issue if MTX >500mg/week (anti-cancer doses)

Loop diuretics
Decreases clearance of MTX, may increase nephrotoxicity potential
Likely only an issue on high doses

Live vaccines

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39
Q

What are the only pain medications that can be used when on methotrexate?

A

NSAID’s are only pain meds that can be used (acet can cause liver dysfx)

  • Methotrexate doses when using cancer doses - really high drug interaction
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40
Q

How can one monitor the efficacy of DMARD’s?

A

Disease activity (ESR, CRP) every 1-3 months initially

Radiographs every 6-12m

Patient assessment:
Chronic disease activity index - administered by HCP:

Health Assessment Questionnaire (HAQ) – done by patient:

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41
Q

Monitoring Safety of Hydroxychloroquine

A

No lab tests required

HYDROXYCHLOROQUINE –> ophthalmic exam baseline and annually after 5 years

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42
Q

Sulfasalazine Safety Monitoring

A

CBCs and LFTs, creatinine

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43
Q

Methotrexate Safety Monitoring

A

CBCs and LFTs, creatinine
Chest x-ray (baseline) – pulmonary toxicity

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44
Q

Leflunomide Safety Monitoring

A

CBCs and LFTs, creatinine

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45
Q

Hydroxychloroquine Efficacy

A

vs. placebo: decreases # affected joints, pain, QoL assessments

vs. other DMARDs: less effective

Does not decrease radiographic damage

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46
Q

Sulfasalazine Efficacy

A

vs. placebo: Decreases symptoms by half

Vs. other DMARDs: typically less effective

Limited monotherapy evidence

Use if other options not tolerated

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47
Q

Methotrexate/Leflunomide Efficacy

A

“Healing” of bone may occur

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48
Q

Rank the relative potencies of the DMARDS

A
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49
Q

Hydroxychloroquine Role in Therapy

A

Useful for early, mild RA

Best tolerated of the DMARDs

Combined with other
DMARDs – monotherapy generally rare

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50
Q

Role in Therapy Sulfasalazine

A

Use if other options not tolerated

Most effective the earlier used

Combined with other DMARDs – monotherapy generally rare

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51
Q

Role in Therapy Methotrexate

A

Highly effective in mod-severe disease

Significantly improves efficacy when combined with biologics

Standard therapy – “backbone”

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52
Q

Leflunomide Place in TX

A

Replacement for MTX if not tolerated

May be added in low doses to MTX

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53
Q

Immune Response in RA Involves….

A

Central to the inflammatory process of RA are monocytes, macrophages and fibroblasts within the synovium, which produce cytokines:

Tumor necrosis factor α (TNF – α)
Interleukins

Overtime, these cause the damage to soft tissue and bone

B and T cells / receptors also a target

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54
Q

What are the main classes of biologic DMARD’s?

A

TNF – α inhibitors
Interleukin – 1 or 6 inhibitors
T-Cell Co-stimulation inhibitors
B-Cell depletors

55
Q

What are some common side effects for all biologics?

A

Nausea
Headache
Diarrhea
Malaise – most common reported one

(Fatigue side effect is short-lived)

56
Q

What are some more serious concerns for biologics?

A

Injection site reactions

Infection rate increase

Neutropenia

Malignant disease

Antibody development

57
Q

Describe the injection site reactions associated with all biologics? How can it be treated?

A

SC –> minor redness and itching, swelling, pain.

Lasts 3-5 days each injection

Severity declines over time

IV –> headache and nausea, rash, hives, fever, chills, fatigue

Hypersensitivity
Anaphylaxis uncommon

Often pre-treat: acetaminophen + antihistamine + steroid ~90 min prior

58
Q

Infection risk with biologic DMARD’s.When is the risk the highest?

A

Infection rate increase:

Age and dose related (Under 65, less of a concern)

Incidence in trials was 5-10%/yr (common) or 2-4%/yr (serious) (compared to placebo)

Common infections: sinusitis, pharyngitis, candidiasis, pneumonia, UTIs

Serious infections: TB, mycobacterial, PCP, CMV, zoster, Hep B/C (opurtunitstic/dormant infections)

Risk highest early in therapy

59
Q

How can the risk of infection associated with biologic DMARD’s be diminished?

A

Screen for TB, Hep C, Hep B, HIV prior to therapy

Up to date on vaccinations (esp. influenza / COVID)

Use biologics with a shorter dosing interval in high-risk patients (shorter interval, can stop, wear off faster)

Educate patient on signs of infection (moderate fever/malaise)

Abatacept may be safest option in high-risk patients

Never use two biologics in combination

If infection occurs: consider temporary discontinuation of biologic

60
Q

What to do if someone on a biologic has an infection occur?

A

If infection occurs: consider temporary discontinuation of biologic

61
Q

Describe the risk of neutropenia associated with biologic DMARD’s. WHy is this a concern?

A

~20% will experience a decrease

Increases severity of infections

Monitoring important

Not a reason to d/c therapy (Small decrease is nothing to worry about)

62
Q

Describe the risk of malignant disease for biologic DMARDS? Management?

A

RA patients have higher cancer risk, confounding data

Overall: No cancer risk increases except for:
Skin cancer
Lymphomas

Avoid biologics in those active malignancies

Preferentially avoid if previous skin cancer

Use rituximab in those with previous lymphoma

63
Q

Describe antibody development as it pertains to the biologic DMARDS?
Drug Concnetration?
Occurs when?
Predicts?
Highest Risk and MAnagement?

A

Clearance of drug increased by body’s defenses

Usually occurs within 2-6 months of starting therapy
May also predict development of auto-immune disease

Infliximab likely highest risk (~50%)
Adalimumab and Etanercept lower risk (~12%)

Methotrexate may lower formation

64
Q

What biologic DMARD’s develop the most antibody development? Effect of antibody development?

A

Does not occur with IL-6 inhibitors

T-cell inhibitors and B-cell depletors: possible effect, but less than TNF-inhibitors

TNF-a inhibitors develops the most

Antibody to the biologic – cleared faster – increased injection site rxns, drug effects wanes over time – more and more to sustain its effect

65
Q

What is the MOA of TNF-a inhibitors?

A

High TNF in RA patients
–> bone erosion

66
Q

What are some examples of TNF-a inhibitors? Differences in efficacy and safety?

A

Adalimumab
Certolizumab
Etanercept
Golimumab
Infliximab

Efficacy and safety equal between the 5 of them

67
Q

What is ACR50?

A

ACR50 – what % of pt’s received a 50% reduction in sx

68
Q

Onset of TNF-a inhibitors

A

Onset – within weeks

69
Q

Efficacy of Tnf-a inhibitors. Effect of efficacy?

A

ACR50 of ~40%

Combination with MTX is more effective (ACR of 60 to 50)

Slow/stop radiographic progression with bone

70
Q

TNF-a combination with MTX. Benefit?

A

Infliximab / Golimumab only indicated in combination with MTX

When combined with MTX, reduce risk of antibody development

71
Q

What are some general principles of TNF-a tx?

A

Infliximab is IV

Subcut is with autoinjectors (can give them themselves)

  • Infliximab is every 8 weeks
  • Dosing intervals – subcut more frequently
  • Biosimilars – some person can get coverage
  • Pregnancy – fairly equal in data
  • Certolizumab – preferred in pregnancy and breast feeding (even better data)

TNF-a not studie din renal impairment – do not use in this group

72
Q

C.I. of TNF-a Inhibitors

A

Active severe infection – temporary d/c

Moderate to severe heart failure (increase risk of heart failure)

73
Q

D.I. of TNF-a Inhibitors

A

Live vaccines – efficacy and infx

Additive immunosuppression with other drugs

74
Q

Adverse Effects of TNF-a Inhibitors (General)

A

Liver enzyme elevations

Heart Failure (unique concern)

Cutaneous (unique concern (plus rituximab))

Autoimmune disease (unique concern

Seizure risk (unique concern)

75
Q

TNF-a and liver enzyme elevations

A

Liver enzyme elevations uncommon (1-5%)

Concern if ALT >5x upper limit normal

Requires periodic monitoring (Baseline then regular monitoring)

76
Q

TNF-a and Heart Failure

A

May cause or worsen existing HF

Use cautiously if needed

Utilize low doses

Evidence is not conclusive

77
Q

TNF-a and Cutaneous

A

Cutaneous (unique concern (plus rituximab))
Cellulitis
Autoimmune skin diseases (eczema, psoriasis)
Skin malignancy

78
Q

TNF-a and autoimmune Disorders

A

Lupus
Vasculitis
Sarcoidosis
Psoriasis

79
Q

TNF-a and Seizure Risk

A

Avoid in patients with seizure disorder

80
Q

Monitoring of TNF-a

A

TB, HIV, Hep B/C screening

CBCs – neutropenia, or agrunlocytosis
LFTs
Baseline and then every 3-6 months

Signs of infection

Ensure vaccinated

81
Q

Which TNF-a inhibitor to choose?WHat to do if lose function over time?

A

Track record and time since approval

Frequency of dosing and route

Cost –> consider those with a biosimilar (inf, eta, ada)

Rheumatologist preference

If loss of effect over time  check antibodies, consider switching or adding MTX

82
Q

Which TNF-a inhibitor can only be administered via IV?

A

Infliximab

83
Q

IL Inhibitors MOA

A

IL-1 and 6 inhibitors antagonize the interleukin receptors reduction in cytokine activity and cartilage damage

84
Q

IL-1 or 6 inhibitors Examples and Place in TX

A

Anakinra (IL-1)* - poorly efficacious in RA, less potent, less s/e
Tocilizumab (IL-6)
Sarilumab (IL-6)

Can be considered first line along with TNF-a

85
Q

IL-1 or 6 Onset

A

weeks, but peak at 5-6 months

86
Q

IL-1 and 6 Inhibitor C.I.

A

Anakinra: None
Tocilizumab: Active infections
Sarilumab: None

87
Q

Anakinra Efficacy Data RA

A

Less anti-inflammatory than other biologic agents

Likely less effective than other biologics

40% achieve ACR20 vs. 27% placebo

Some radiographic improvement

88
Q

Tocilizumab/Sarilumab IL-1 and 6 Inhibitor Efficay

A

~40% achieve ACR50 vs. 10% placebo

Similar or potentially more effective than TNF inhibitors (adalimumab)

Some radiographic improvement

89
Q

IL-1 and IL-6 Dosing Adjustments

A

Anakinra:
CrCL >30ml/min: No adjustment
ESRD: Dose every other day

Tocilizumab and Sarilumab
CrCL >30ml/min: No adjustment

IL-1 and 6 inhibitors are only ones that have robust renal impairment data

90
Q

Anakinra A/E

A

Injection-site reactions and infections

Overall serious adverse effects similar to placebo rate

Headache and Nauseau

91
Q

A/e of Tocilizumab/Sarilumab

A

GI perforation (unique + rituximab)
Rare
Caution if at risk of GI issues
Ulcer and sepsis risk

Dyslipidemia (unique): ↑ TC / TG and ↓HDL

Antibody development not linked to decreased effect (unique)

Hypertension – small increase

Other concerns similar to TNF inhibitors (common ADRs, LFTs, infections,

92
Q

What other drug is often started alongside Tocilizumab / Sarilumab?

A

Other factors for metabolic – often will see people on statins here to deal – use target high doses of statin

93
Q

D.I. of the IL-1 and 6 Inhibitors

A

Drug Interactions

All:
Decreased IL1 or 6 activity = Increased CYP activity

Additive immunosuppression
Live vaccines

Tocilizumab
Simvastatin increased 4-10x
Choose any other statin here

94
Q

Monitoring of IL-1 and 6 Inhibitors

A

Anakinra: Baseline CBC, LFTs, creatinine; then every 3-6 months

Tocilizumab / Sarilumab:
Baseline CBC, LFTs, creatinine; repeating in 4-8 weeks after starting, then every 3-6 months
Lipid panel
Blood pressure
Latent / active TB, Hep B/C screening

95
Q

T-cell Co-Stimulation Inhibitor MOA and Use

A

Inhibits T-cell activation

Used if inadequate response to DMARDs or TNF inhibitors

Monotherapy or combination with traditional DMARDs (MTX)

Includes: Abatacept

Less data than other biologics

96
Q

Efficacy of T-cell Co-Stimulation Inhibitor

A

41% achieved ACR50 vs. 20% placebo at one year

Dosage and administration

97
Q

Adverse Effects of T Cell Co-Stimulation Inhibitor

A

Similar to TNF inhibitor – infections (likely lower risk), neutropenia, common ADRs

COPD exacerbations (unique)

No impact on liver function (unique)

Hypertension

Blood glucose increased

Unknown if antibodies impact efficacy or safety

98
Q

Monitoring of T-Cell Co-Stimulation Inhibitor

A

Signs and symptoms of infection
TB and hepatitis screening
CBCs, creatinine
Blood pressure
Blood glucose – not mandatory – if pre-diabetic or risk factors

99
Q

B-cell depletor MOA, Example

A

B-cells central to immune memory and the production of auto-antibodies

B-cell depletors bind to B-cells to cause lysis

Includes: Rituximab

100
Q

B-cell Depletor Use, Onset, Efficacy Data

A

Only studied in combination with MTX AND failure on a TNF inhibitor

Onset – May be delayed up to 6 months

Efficacy data:

ACR50 of 43% vs. 13% placebo
Does not work well in RF-negative patients
No halt of radiographic progression

101
Q

B-cell Depletor Times of Administration

A

2 dose course: 1g IV infusion given two weeks apart

Must pretreat with methylprednisolone, acetaminophen and diphenhydramine

Re-treat when needed (~6 months) – some only need to retreat every 1-2 years
Some require two courses for efficacy

Withhold hypertension medication morning of infusion

Pre-tx protocol – methylprednisone, diphenhydramine, and acetaminophen – reduce risk of anaphylactic rxn

102
Q

A/E Of B-cell Depletor

A

Infusion reactions tend to be more rapid, but mild and brief

Serious infection rate is non-existent initially; then increases on repeat courses

Hypertension
GI perforation
Blood glucose increase

Mucocutaneous reactions (SJS, TEN) – reported, more common than other biologics

Antibody formation likely leads to increased infusion reactions and decreased efficacy

103
Q

B-cell Depletor Monitoring

A

Baseline CBC, LFTs, creatinine
TB, Hepatitis B/C screening

104
Q

What drives us to choose a certain biologic? (REMEMEBER)

A
105
Q

Biologic DMARD’s Place in TX

A

Biologics considered once other options have been tried
Exception: Initial severe case of RA

TNF – α inhibitors
Initial biologic of choice for most

Interleukin – 1 or 6 inhibitors
Anakinra: for those risk averse or who cannot tolerate other DMARDs
Tocilizumab / Sarilumab: for moderate to severe RA, often in combination with MTX
Both: if antibodies to others biologic DMARDs have formed

T-Cell Co-stimulation inhibitors
When traditional DMARDs or TNF inhibitors have failed

B-Cell depletors
Combo with MTX when others have failed
Use if history of lymphoma

106
Q

Janus-Kinase Inhibitors MOA, Use, Examples, Role in TX

A

Janus Kinase are a group of enzymes responsible for enabling interleukin signalling

Indicated preferably in combination with MTX
May be used as monotherapy if MTX intolerance
Other combinations not recommended

Includes: Tofacitinib, Baricitinib, Upadacitinib

Place in therapy: Last line option

107
Q

Efficacy of Janus Kinase Inhibitor

A

Combined with MTX: ACR50 46% vs. 20% placebo

Monotherapy: ACR50 of 38%

108
Q

A/E Janus Kinase Inhibitor

A

Similar to TNF inhibitors and other biologics, including:

HTN
Infections / cytopenia
LFTs / hepatotoxicity
Bradycardia
GI perforation

Drop out rates of ~10%

No concern about antibody development

109
Q

C.I. Janus Kinase Inhibitor

A

Use during severe infections

110
Q

Warnings Janus Kinase Inhibitor

A

New data - CV risk (MI, clots) - NNH 113/5yrs
New data - Malignancy (lung cancer, lymphoma)
GI perforations
Bradycardia
Dyslipidemia

111
Q

D.I. Janus Kinase Inhibitors

A

Tofactinib / upadacitinib are major 3A4 substrates; baricitinib is a minor 3A4 substrate
Live vaccines
Additive immunosuppression

112
Q

Janus Kinase Inhibitor MOnitoring

A

Latent TB testing
Lipid profile
CBCs every 3-6m months
LFTs

113
Q

Janus Kinase Inhibitor Preganancy

A

Pregnancy / lactation – limited data, use better studied alternatives

114
Q

Corticosteroids in RA Use, MOA

A

Important tool for RA treatment

Majority of patients will use in course of disease

Likely has DMARD properties and decreases early progression of RA

Significant controversy on optimal utilization

115
Q

Corticosteroids Efficacy. Main Benefit?

A

Reduces joint tenderness more than placebo and NSAIDs
Reduces pain more than NSAIDs
Improved QoL measures
Small radiographic progression decrease

Main benefit: subjective symptomatic improvement

116
Q

Tx Modalities of Corticosteroids in RA

A

1) Short-term use
Doses of 10-15mg prednisone equivalent per day (low dose)
Taper and d/c as symptoms improve
Limited safety issues if dose / duration kept low

2) Chronic Use
Doses of 5-10mg prednisone equivalent per day indefinitely
Long-term steroid safety issues become apparent
Increases need for monitoring and adjunctive treatments

3) Pulse Therapy

Administer high doses for a few days
Methylprednisolone 1000mg IV for 3 consecutive days once monthly for 6-8 months

Safety issues: cardiovascular collapse, hypokalemia, myocardial infarction, severe infection

Considered a last resort option in RA

117
Q

Corticosteroids Onset

A

Within days

118
Q

Corticosteroids S/e

A

Cataracts
Dyslipidemia
Hyperglycemia
Osteoporosis
Weight gain

119
Q

Intra-articular Injections of Corticosteroids

A

Safe and effective when done by experienced MD
Effects dramatic, but temporary
Same joint should not be done more than once per 3 months
Considered “palliative”
Rest joint for 3 days after injection

120
Q

Issues with Intra-articular injections of corticosteroids

A

tendon rupture
acute synovitis
localized skin hypopigmentation
septic arthritis

121
Q

Guideline Approach for Corticosteroid USage

A

Consider for flares or as “bridging”

Aim for a max dose of 10mg/d

Never use as monotherapy

Find minimum dose/duration

Consider avoiding in those more at risk of steroid side effects

122
Q

NSAID’s Use in RA

A

Provide high dose NSAIDs at initial diagnosis

Use for at least 2 weeks for maximum benefit

Cautiously combined with other treatments (e.g. corticosteroid)

Consider providing GI protection

Should not need to use chronically

123
Q

Do NSAID’s help with the underlying dx process?

A

Do not do anything to effect underlying disease process

GI Risk and Bleed heightned with steroids and NSAID

124
Q

Other analgesics used in RA

A

Acetaminophen sometimes added (2g/day)

Avoid opioids
Limited evidence in RA
Proper DMARD use and non-pharm is greater benefit

125
Q

Combination TX for RA

A

NSAIDs + Glucocorticoids can be added to any regimen (extra caution with NSAID and Steroids together)

MTX can be added to all biologics

LEF + biologics similar to MTX + biologics

tDMARD double therapy - any two of MTX, SSZ, HCQ or LEF

tDMARD triple therapy - MTX + SSZ + HCQ
ACR50 of single, double or triple combo tDMARDs: 29%, 40% and 55%

Biologic + two tDMARDs – unclear benefit/harm; “reasonable” in guidelines

Recommend AGAINST multiple biologics

ACR50 of MTX vs. MTX + biologic: 20% vs. 58%

126
Q

Flare Management for RA

A

Intraarticular glucocorticoid if few joints
Initiate / increase glucocorticoid
Consider increasing DMARD doses
Add new DMARDs if frequent flares

127
Q

First-line Initial therapy approach for low disease activity?

A

Conditional recommendation, in order of preference for initial therapy: HCQ > SSZ > MTX > LEF

Monotherapy preferred

128
Q

First-line Initial therapy approach for moderate-to-high disease activity?

A

Methotrexate strongly recommended over HCQ or SSZ

Methotrexate conditionally recommended over leflunomide

Methotrexate monotherapy recommended over double or triple traditional DMARDs therapy

Methotrexate monotherapy conditionally recommended over combo with biologics

129
Q

When monotx fails to achieve goal of therapy?

A

Preferentially add a biologic DMARD instead of SSZ/HCQ

130
Q

When should RA tx be escalated?

A

Failure to achieve remission or acceptable disease activity after 3-6 months at optimal doses

Inability to taper steroids

Recurrent flares (2 or more flares per year; escalate tx if happening; 1 flare per year still a strong consideration)

Disease progression on Xray

131
Q

Pregnancy: Agents to Avoid

A

Must discontinue unsafe medications

MTX – male and female - stop for 3 months prior to conception

Leflunomide – male and female – take cholestyramine, measure levels until <0.02mg/ml, then wait an additional 3 months

132
Q

Goal of TX in Pregnancy

A

Achieve remission on safe options:

HCQ and SSZ good options

All biologic agents, except rituximab, have favourable safety profiles

Certolizumab has the most robust data; compatible with all trimesters

133
Q

Peri-Preganancy RA Options

A

Corticosteroids may be used sparingly

Ensure folic acid 5mg/d if previous MTX use

Cautious use of NSAIDs – C.I. in third trimester, strong precaution in 1st trimester, 2nd semester is safer

134
Q

Post-partum RA Tx

A

Flares common

Return to pre-pregnancy regimen/doses if compatible with breastfeeding

135
Q

Lactation RA Tx

A

NSAID use (ibuprofen preferred) acceptable
Low dose prednisone (<20mg/d) compatible
HCQ and SSZ safe to continue
TNF-inhibitors, IL-6 inhibitors safe
Continue to avoid MTX and LEF

Other agents: limited data or not studied

PHAR 255 Exam 2 (5 decks)

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