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PDAT4 > 25 - Rheumatoid Arthritis > Flashcards

25 - Rheumatoid Arthritis Flashcards

(46 cards)

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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

Study These Flashcards
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?

Study These Flashcards
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

Study These Flashcards
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?

Study These Flashcards
A

DMARD therapy should be MODIFIED in:

Repetitive FLARES

Unacceptable DISEASE ACTIVITY

Progressive JOINT DAMAGE

23
Q

Biologic DMARDS
RA Therapy

Study These Flashcards
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

Study These Flashcards
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
**Biologic DMARDS - USE / INDICATIONS** RA Therapy
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
**Biologic DMARDs: ADRs** RA Therapy
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
**Anti-TNF Agents: USE** RA Therapy
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
**Anti-TNF Agents: ADRs** / **Contraindications** RA Therapy
_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
**What needs to be monitored / tested b4 taking: ANTI-TNF AGENTS?**
**_TB SKIN TEST_** **_HEP B_** surface Ag & core Ab _Monitor:_ **CBC - Neutropenia LFTs - Hepatotoxicity**
30
**ANTI-TNF Agents Dosing / Administration**
**_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
**Abatacept** Biologic DMARD for RA
**_*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
**Rituximab Considerations / Indications** Biologic DMARD for RA
**_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
**Rituximab Dosing / ADR** Biologic DMARD for RA
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
**Tocilizumab / Sarilumab ADR / Contraindications** Biologic DMARD for RA ## Footnote **Tocilizumab = IV + SC** **Sarilumab = SC**
*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
**JAK-Inhibitors** **CONTRAINDICATIONS** RA Therapy
* **_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
**Tofacitinib = Xeljanz** Considerations RA Therapy
**_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
**Baricitinub = Alumiant** Considerations RA Therapy
**_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
* *JAK-Inhibitor ADRS** * *Tofacitinib / Baricitinib**
**_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
**BREASTFEEDING** Concerns for **BIOLOGICS / JAK-I**
**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
**PREGNANCY** Concerns for **Biologics / JAK**
_***AVOID for* 3-6 months b4 pregnancy**_ anakinra / abatacept / rituximab Tocilizumab / saralumab / tofacitinib _Safest is:_ * *certolizumab / etanercept** * *Anti-TNF's**
41
**What RA drug should be avoided for patients with _COPD?_**
**_ABATACEPT_** orencia ## Footnote **Anti-TNF --\> CTLA4** **Biologic drug**
42
**Which RA drug has the ADR of THROMBOSIS** arterial & venous w/ higher doses
**_BARICITINIB_** olumiant **JAK 1 / 2 Inhibitor** Also: **GI PERFORATION** **LIPID CHANGES** ↑TC / LDL / TG / HDL
43
Monitoring for: * *_IL-6 Inhibitors_** * *Tocilizumab / Sarilumab** * *_Jak Inhibitors_** * *Tofacitinib / Baricitinib**
**_CBC**_ & _**LFTs_** @baseline & q4-8 wks --\> q3mo **_LIPID PANEL_** 4-8 weeks after start --\>q6mo **_Infections_**
44
**Which RA drug has drug interactions with 2C19?** **Cyp2c19 Inhibitors --\> *reduce dose*** **Fluoxetine / PPIs Indomethacin / Ketoconazole Isoniazid / Probenecid**
* *_TOFACITINIB_** = Xeljanz * *Jak 1/3 inhibitor** ## Footnote **Need to reduce dose to 5mg f so** **Also a CYP3A4 issue**
45
**Efficacy Monitoring for RA** **What Labs?**
* 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
**Toxicity Monitoring for:** **MTX / SZA / Leflunomide**
**_CBC_** **_SCr_** **_LFT_** @ baseline and more _For MTX_: **also CXR** for **pulmonary changes**

PDAT4 (34 decks)

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