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PDAT4 > 25 - Rheumatoid Arthritis > Flashcards

25 - Rheumatoid Arthritis Flashcards

1
Q
  • *Pathophysiology**
  • *RA**
A

Effects of Pro-inflammatory cytokines:

  • *TNF** / IL-1 / IL-6
  • *OUTWEIGH** those of anti-inflammatory cytokines

Chronic Inflammation & Proliferation of
SYNOVIAL TISSUE
which invades the cartilage –> bone surface –> erosions

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2
Q

Clinical Presentation
RA

A
  • *Synovitis**
  • *SYMMETRICAL joint swelling**
  • *PIP / MCP**

Morning Stiffness > 1 hour

Symptoms in Small Joints
Hands / feet

Joint Pain & Tenderness, Muscle Aches

Low grade Fever
Weight Loss / Fatigue / Weakness / Loss of Appetite

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3
Q

ACR Diagnostic Criteria

A

AT LEAST 4 of 7

Morning Stiffness

Arthritis of > 3 joint areas

Arthritis of hand joints

Symmetric arthritis

Rheumatoid Nodules

RF = Serum rheumatoid Factor

Radiographic Changes

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4
Q

ACR/EULAR Criteria for Diagnosis

  • *Effort to DIAGNOSE EARLIER DISEASE**
  • not necessarily for clinical diagnosis*
A

> 6 points = DEFINITE RA

4 Domains, graded on points
Joint Involvement
Quantity of joints, swollen or tender on exam

Serology
RF // CCP antibody

Acute Phase Reactants

Duration of Symptoms

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5
Q

Non-Pharmacologic Therapy
RA

A

STOP SMOKING

Rest
8 hours of sleep // naps

  • *Physical Therapy**
  • *Passive range of motion / Exercise**

Occupational Therapy

Achieve
IBW

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6
Q
  • *Corticosteroids**
  • *RA Therapy**

Oral: Prednisone

Injectable: Triamcinolone Acetonide
MP Sodium Succinate

A

NON-DISEASE MODIFYING
controls symptoms quckly, within days
SOME anti-erosive effects –> NOT completely non-disease modifying

Added to other therapy in ACUTE flares
or used Chronically @ low doses <7.5 mg/day

Typically used SYSTEMICALLY
but may be use intraarticularly –> into JOINTS

limited by many LONG-TERM ADR’s > 3 months

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7
Q

Considerations b4 starting DMARDS
​RA Therapy

A
  • *Start DMARD - ASAP** in most patients
  • continue Coticosteroids or NSAID until effect is seen*

Pt Specific factors or History effecting DRUG SELECTION
MTX + Alcohol
Abatacept + COPD
CHF + anti-TNF agents

AVOID LIVE VACCINES
while on biologics (herpes zoster)

Killed Vaccines are fine

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8
Q

Non-Biologic DMARDS
​RA Therapy

A
  • *Methothrexate = MTX**
  • avoid alcohol*

Sulfasalazine = SSZ

Hydroxycholoroquine = HCQ

Leflunomide = LFN

Azathioprine / Ninocycline / Gold Sals / Cyclosporine

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9
Q

Methotrexate - Indication / MOA
​RA Therapy

A

CORNERSTONE OF RA THERAPY
typically the INITIAL DMARD in many cases

Non-Biologic DMARD
1-2 Month onset

DIHYDROFOLATE REDUCTASE INHIBITOR
–> inhibits PURINE synthesis –> reduced cell turnover
inhibits production ofIL-1

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10
Q

Methotrexate - DOSE
​RA Therapy

A
  • *10-25 mg po WEEKLY**
  • *2.5 mg tablets** –> 1 BIG DOSE on ONE DAY
  • renally dosed*

Taken with:
Folic Acid 1-3mg/day
to decrease:
stomatitis / N+D / Alopecia

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11
Q

Methotrexate - ADR / CI’s
​RA Therapy

A

ADR:

  • *HEPATOTOXICITY**
  • *lung disease / myelosupression / PREGNANCY CAT X**

CI’s

  • *AVOID / MINIMIZE ALCOHOL**
  • relatively contraindicated in* RENAL / LIVER impairment (renally dosed)
  • *significant lung disease**
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12
Q

Leflunomide - Indication / MoA
​RA Therapy

Non-Biologic DMARD

A

Alternative to MTX
or can be used in COMBINATION (lower dose 10mg QD)

LONG HALF LIFE
due to enterohepatic recirculation

  • *INHIBITS DIHYDROOROTATE DEHYDROGENASE**
  • inhibit PYRIMIDINE synthesis –> lymphocyte production*
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13
Q

Leflunomide - DOSE / ADR
Non-Biologic DMARD
RA Therapy

A

100 mg f3d –> then 20mg qd

EQUAL EFFICACY + SAME TOXICITY
As MTX

NOT FOR PREGNANCY OR BREAST FEEDING
requires a :
WASH OUT –> before fertility
since LONG HALF LIFE –> 2 YEARS

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14
Q

Hydroxychloroquine - Indication / MoA
Non-Biologic DMARD
​RA Therapy

A

Interferes with ANTIGEN PROCESSING
in macrophages + other APCs –> down regulation of immune response

Mild Effects + *SLOW* Onset (2-6mo)
so used in COMBO w/:
SSZ or MTX

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15
Q

HCQ - Dose / ADR
Non-Biologic DMARD
​RA Therapy

A
  • *200 mg po BID**
  • or 400mg QD*

Well Tolerated - occasional rash or GI

Potential for:
OCULAR TOXICITY​
Cornea -> reversible
Retinopathy –> IRREVERSIBLE
loss of centreal/peripheral/night vision

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16
Q

Which Medication causes RETINOPATHY?
& what are the risk factors?

A

HYDROXYCHLOROQUINE = HCQ

Retinopathy is IRREVERSIBLE
continued deteriotion in vision AFTER DC OF DRUG

Risk Factors:
Daily Dose > 5mg/kg (ABW)

Duration of use >5 years w/o other RF

Renal impairment / Tamoxifen use / Previous eye disease

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17
Q

What tests must be done if taking HCQ?

A

Baseline Eye Exam within 1 year of initiation
due to RETINOPATHY

Annual Screening after 5 years if no other RF

sooner than 5 years if Risk Factors

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18
Q

Sulfasalazine (SSZ) - Indication / MoA
Non-Biologic DMARD
RA Therapy

A

Often used in combination w/:
HCQ +/- MTX

1-3 Month Onset

MoA is Unknown in RA

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19
Q

SSZ - Dose / ADR / CI
Non-Biologic DMARD
RA Therapy

A

500-1500mg po BID WF

WARFARIN DRUG INTERACTION

ADR:
GI ADVERSE EFFECTS
common, tend to wane after first few months, take WF
lessened by starting low –> slow w/ dose
RASH
uticaria / leukopenia / alopecia / elevated hepatic enzymes
yellow-orange skin or urine

20
Q

SSZ
pregnancy / Fertility concerns?

A

Pregnancy
OK if <2g/day

Breast Milk
Yes, but considered safe

  • *REDUCES SPERM COUNT**
  • but reverisble after 2-3 months*
21
Q

LFN WASH OUT

A
  • to prevent TERATOGENICITY*
  • Long half life of ~2 years*

CHOLESTYRAMINE
8g TID for 11 days

CHARCOAL SUSPENSION
50g BID for 11 days

Goal:
Teriflunomide concentration < 0.02mg/L
verify with 2nd test after 14 days

22
Q

When to ADVANCE DMARD therapy?

A

DMARD therapy should be MODIFIED in:

Repetitive FLARES

Unacceptable DISEASE ACTIVITY

Progressive JOINT DAMAGE

23
Q

Biologic DMARDS
RA Therapy

A

Anakinra = Kineret
LESS EFFECTIVE, NOT USED OFTEN
Recombinant IL-1 receptor antagonist

Abatacept = Orencia
works on t-cell receptor resulting in down regulation of T-cells

Rituximab = Rituxan
works on CD20 on B-cells –> B-cell depletion

  • *Tocilizumab / Sarilumab**
  • *IL-6 receptor inhibitors**
24
Q

Basics of BIOLOGIC DMARDS
RA Therapy

A

Parenteral Administration

WORK QUICKLY
days - weeks , vs months for non-biologic DMARDS
significant improvement within 12-16 weeks

Serious side effects / High Costs

25
Q

Biologic DMARDS - USE / INDICATIONS
RA Therapy

A

Moderate to severe RA

Often used in those who have FAILED MTX
due to intolerance / unsatisfactory response

Steroid Sparing Agent

Used alone or in combo with NON-BIOLOGIC DMARD
combination therapy is BETTER

26
Q

Biologic DMARDs: ADRs
RA Therapy

A

Many ADR are overlapping (bacterial infxns)
do NOT combine with >1 biologic DMARD

INFECTION
update vaccinations, but AVOID live vaccines
consider DC in acute infxn // hold b4 procedures

Malignancy / Neutropenia / Injection Site Reactions

27
Q

Anti-TNF Agents: USE
RA Therapy

A

Generally, FIRST LINE Biologic DMARD
due to:
Efficacy / fast onset / clinical experience / SC DOSING

no evidence that any 1 anti-tnf > others

  • *Reasonable to try SECOND anti-TNF**
  • *after FAILURE of 1st**
  • AB -formation*
28
Q

Anti-TNF Agents: ADRs / Contraindications
RA Therapy

A

INFECTION

  • *TB SKIN/BLOOD TEST** prior to use
  • -> if positive check CHEST X-RAY
  • *LTB (latent TB) ID’d then start treatment of Isoniazid**
  • *Check HEP B surface Ag_ & _core Ab**
  • before start of anti-TNF*

MALIGNANCY

  • *above baseline eleveted risk in RA patients**
  • already high w/o drugs*
  • *Leukemia / Lymphoma**
  • *HSTCL / Skin Cancer**

NEUTROPENIA / HEPATOXICITY
need to monitor CBC / Liver

29
Q

What needs to be monitored / tested b4 taking:
ANTI-TNF AGENTS?

A

TB SKIN TEST

HEP B
surface Ag & core Ab

Monitor:
CBC - Neutropenia
LFTs - Hepatotoxicity

30
Q

ANTI-TNF Agents
Dosing / Administration

A

most is available as SUBQ

  • EXCEPT:*
  • *Infliximab = IV (3mg/kg over 2 hours)**

Golimumab = IV (2mg/kg over 30 min)
also available SQ monthly

31
Q

Abatacept
Biologic DMARD for RA

A

avoid with patients with COPD
they have more ADRs

  • *CTLA-4**
  • inhibits T-cell activation*
  • *IV & SC**
  • longer time to effect vs Anti-TNF agents*
32
Q

Rituximab
Considerations / Indications
Biologic DMARD for RA

A

safest drug for CANCER PATIENTS / TB

recommended biologic for pts w/:

  • *Treated Cancer within 5 years**
  • no evidence of an increase of malignancy in RA patients*
  • *no need to screen for TB**
  • no evidence for increased incidence of TB*

CD20 binding –> depletes B-cells

Does NOT require continuous therapy
to maintain response, lasts 4mo >1 year

33
Q

Rituximab
Dosing / ADR
Biologic DMARD for RA

A

1000 mg IV INFUSION
over course of 2 infusons 2 weeks apart –> repeat 16-24 weeks later
little dosing

ADR: INFUSION REACTIONS (1st dose)

  • *Screen for HEP B + C**
  • reactivation*
34
Q

Tocilizumab / Sarilumab
ADR / Contraindications
Biologic DMARD for RA

Tocilizumab = IV + SC

Sarilumab = SC

A

decrease IL-6 mediated signaling

do NOT start if any of the following:
ANC < 2000
ALT or AST > 1.5x ULN
PLT < 100k(Tocilizumab) //PLT < 150k (Sarilumab)

ADR:
GI PERFORATION** // **DYSLIPIDEMIA
eleveated LFTs / neuropenia / malignancy / infxns

35
Q

JAK-Inhibitors
CONTRAINDICATIONS
RA Therapy

A
  • do NOT start if:*
  • *ANC < 1000**
  • *Lymphocytes < 500**
  • *Hb <9** (tofacitinib) // Hb <8 (baricitinib

do NOT combine with BIOLOGIC

  • AVOID in patients taking:*
  • *OTHER potent immunosuppresive drugs**:
  • *AZA / TAC / CSA**
36
Q

Tofacitinib = Xeljanz
Considerations
RA Therapy

A

JAK-Inhibitor

  • *70% LIVER METABOLISM**
  • *CYP 3A4 / 2C19 –> DRUG INTERACTIONS**
  • lossess effectiveness with inducers*
  • Reduce to 5mg PO qd in patients wtih:*
  • *Renal Insufficiency** / moderate Hepatic Impairment
  • *enzyme inhibitors (ketoconazole / fluconozole)**

NOT FOR BREASTFEEDING

37
Q

Baricitinub = Alumiant
Considerations
RA Therapy

A

JAK-Inhibitor

Also CYP3A4 but no meaningful DI’s

  • *75% Renal ELimination**
  • NOT RECOMMENDED with* CrCl < 60

DI with:
Strong inhibitors of OAT3 = Probenecid

ADR:
THROMBOSIS = Arterial + Venous
with high doses

38
Q
  • *JAK-Inhibitor ADRS**
  • *Tofacitinib / Baricitinib**
A

GI PERFORATION

LIPID CHANGES
INCREASE in TC / LDL / TG / HDL

For Baricitinib:
THROMBOSIS - Venous / arterial

Common ADR for both:
URI / HA / HTN / nasoparyngitis
Infections
malignancy / hepatotoxicty / lymphopenia / neutropenia

39
Q

BREASTFEEDING
Concerns for BIOLOGICS / JAK-I

A

Most are LARGE MOLECULES
unlikely to penetrate into breast milk in large quantities
likely destroyed by GI tract if present

EXCEPT FOR
TOFACITINIB
small molecule –> can get into breast milk

40
Q

PREGNANCY
Concerns for Biologics / JAK

A

_*AVOID for* 3-6 months b4 pregnancy_
anakinra / abatacept / rituximab
Tocilizumab / saralumab / tofacitinib

Safest is:

  • *certolizumab / etanercept**
  • *Anti-TNF’s**
41
Q

What RA drug should be avoided for patients with
COPD?

A

ABATACEPT
orencia

Anti-TNF –> CTLA4

Biologic drug

42
Q

Which RA drug has the ADR of
THROMBOSIS
arterial & venous

w/ higher doses

A

BARICITINIB
olumiant
JAK 1 / 2 Inhibitor

Also:
GI PERFORATION
LIPID CHANGES
↑TC / LDL / TG / HDL

43
Q

Monitoring for:

  • *IL-6 Inhibitors**
  • *Tocilizumab / Sarilumab**
  • *Jak Inhibitors**
  • *Tofacitinib / Baricitinib**
A

CBC** & **LFTs
@baseline & q4-8 wks –> q3mo

LIPID PANEL
4-8 weeks after start –>q6mo

Infections

44
Q

Which RA drug has drug interactions with
2C19?

Cyp2c19 Inhibitors –> reduce dose
Fluoxetine / PPIs
Indomethacin / Ketoconazole
Isoniazid / Probenecid

A
  • *TOFACITINIB** = Xeljanz
  • *Jak 1/3 inhibitor**

Need to reduce dose to 5mg f so

Also a CYP3A4 issue

45
Q

Efficacy Monitoring for RA

What Labs?

A
  • reduction in inflammatory markers:*
  • *ESR_ or _CRP**
  • no longer RH or Anti-CCP*

Patient Global Assessment

DAS** or **DAS28

Joint Pain / Morning Stiffness / Active inflammation / Xray / Fatigue

46
Q

Toxicity Monitoring for:

MTX / SZA / Leflunomide

A

CBC

SCr

LFT

@ baseline and more

For MTX: also CXR for pulmonary changes

PDAT4 (34 decks)

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