32/33 - MS Flashcards
Diagnosis of MS
McDonald Criteria
Clinical Attacts + MRI Results
Demonstration of
MS Lesions seperated in TIME & SPACE
Dissemination in Time & Space = DIT & DIS
Occurance of:
> 2 Seperate Neurological Events
representing:
Different sites of dmg in CNS
Definition of an
MS RELAPSE
New** or **Worsening
of previous symptoms lasting >24 hours
Has to be:
Seperated
from the previous relapse by >30 days
What is CIS?
Clinically Isolated Syndrome = CIS
First Clinical Episode
early neurological episode consistant w/ demyelinating process
must last >24 hours
does not completely fulfill diagnostic criteria
May or may NOT go on to develop MS
What is
RRMS
Relapsing / Remitting MS
85% of MS cases @ onset
Characterised by:
Acute Relapses
VVV
followed by periods of COMPLETE or PARTIAL remission
What is
SPMS
Secondary Progressive MS
ALWAYS BEGINS AS RRMS
most patients will progress to SPMS
Progressive Worsening of Neurological functioning over time
What is
PPMS?
- *PRIMARY progressive MS**
- typically do NOT experience RRMS*
15% of cases
Worsening of neurological symptroms
FROM ONSET
Acute Relapse Treatment for MS
Medication / Dose / Effect
METHYLPREDNISOLONE
500 - 1000 mg/d for 3-5 days
↓lymphocytes, ↓inflammation, ↓edema
no effect on disease progression
but better to start SOONER than later
Shortens Duration & Severity of attacks/relapses
INF-Beta
ARR% - Indications - MoA
30%
RRMS & CIS
Reduces inflammation by:
- inhibiting T-cell*
- *Activation / Proliferation / migration into CNS**
ADR’s & Monitoring
INF-Betas
Rebif / Plegridy / Avonex
Betaseron / Extavia
Flu-Like Symptoms** + **Injection Site Reactions
use NSAIDS / Tylenol prior to injection
Depression
ELEVATED LFTS
need to monitor 1/3/6months
decreased RBC
cbc 1/3/6 months
AVONEX
Drug Class / Admin
INF-beta
for MS - 30%
LFT / CBC
- *Weekly IM injection**
- Flu-like symptoms + inj site reactions + depression*
PLEGRIDY
Drug Class / Admin
INF-beta
for MS - 30%
LFT / CBC
- *SUBQ** - q14days
- Flu-like symptoms + inj site reactions + depression*
Beteseron / Extavia
Drug Class / Admin
Betaseron = Extavia
SAME DRUG - different maufacturer
INF-beta
for MS - 30%
LFT / CBC
- *SUBQ -> QOD**
- Flu-like symptoms + inj site reactions + depression*
Rebif
Drug Class / Admin
INF-beta
for MS - 30%
LFT / CBC
- *SUBQ** - TIW
- *two titration schedules** due to ADRs
- Flu-like symptoms + inj site reactions + depression*
Which DMT for MS
is administered IM?
AVONEX
INF-beta
for MS - 30%
LFT / CBC
Weekly IM injection
Flu-like symptoms + inj site reactions + depression
Which MS drugs require
LFTs?
“LFT = LE F-I-T”
Fingolimod
INF-Betas
Rebif / Plegridy / Avonex / Betaseron = Extavia
Teriflunomide = Aubagio
BBW -> severe liver injury
Daclizumab
BBW for hepatic injury –> REMOVED from market
Copaxone = Glatiramer Acetate
ARR% - Indications - MoA
30%
CIS - RRMS
Synthetic Polypeptide mimicking myelin basic protein (MBP)
inhibits antigen presentation & T-cell Activation
Which MS drug is recommended for
WOMEN looking to get PREGNANT?
COPAXONE
Glatiramer Acetate
30%
ADRs & Monitoring
Copaxone
Glatiramer Acetate
LIPOATROPHY
@ injection site –> loss of SUBq fat
- *Injection Site Reactions**
- *SUBQ**
- *Transient Post-Injection Reactions**
- flushing / chest tightness / palpitation / anxiety*
ONLY PREGNANCY CLASS B DMT for MS
Natalizuab
Tysabri
ARR% - Indications - MoA
68%
HIGHEST EFFICACY, typically last line
RRMS
Patients with poor response / failed alt therapies
IV Infusions Every Month
Humanized MAB
binds a4 subunit of integrin on surface of lymphocytes
prevents entry into CNS
ADRs & Monitoring
Natalizumab
Tysabri
BBW - PML
demyelinating disease affecting CNS in IMS pts
TOUCH PROGRAM
3 Risk Factors
>2 years treatment + JCV ABs + Prior IMS therapy
Opportunistic Viral infection (by JC virus)
Death or Severe Disability
What are RISK FACTORS for PML
when starting Natalizumab?
- *Duration of Treatment**
- *> 2 years**
+ JCV Antibodies
Prior IMS therapy
AZA - MTX
if any of these factors –> HUGE RISK for PML
Which MS drugs have risk for
PML?
PML -> T-N-F
Tecfidera - Natalizumab - Fingolimod
Dimethyl Fumarate = Tecfidera
Natalizumab
BBW - Touch program
Fingolimod
Fingolimod
Gilenya
ARR% - Indications - MoA
54%
- *RRMS**
- *ORAL DAILY CAPSULE**
- *S1P inhibitor**
- *redues migration of peripheral lymphocyes –>CNS**
Which MS drug is:
CONTRAINDICATED WITH CV ISSUES?
FINGOLIMOD
Oral - 54%
MI - Unstable Angina - Stroke - HF
within 6 months
2nd / 3rd degree AV block
Class 1 / 3 Antiarrythmatic Drugs
Qtc interval > 500
ADRs
FINGOLIMOD
- *PML REPORTED**
- *Leukopenia + Lymphocytopenia**
- *First dose BRADYcardia**
- *Contraindicated for CV patients**
- *Bronchitis**
- mild reduction in* Lung FXN
Risk of HERPES viral infection
check VZ igG Ab
HT / Edema
2 Month elimination –> wait for pregnancy
Monitoring for
FINGOLIMOD
- *Initial Monitoring Procedures**
- (MUST BE REPEATED IF TREATMENT IS INTERRUPTED)*
- *CBC + LFT**
- *Opthalmolgy Exam +** VZ IgG Titer ( Herpes )
- *EKG Baseline**
First Dose Admin Monitoring
VS + Hourly BP/HR for 6 hours
Post-Dose EKG
Opthalmic exam + CBC + LFT
Repeat 1 Initial Monitoring if… After Medication Initiation:
- *> 1 day during the first 2 weeks**
- *> 7 days during weeks 3-4**
- *> 14 days after > 1 month**
Teriflunomide
Aubagio
ARR% - Indications - MoA
30%
- *RRMS**
- *7 & 14 mg Tablet QD** ORAL
- reduction is ONLY seen with 14mg/day*
MoA is not well known
Which MS drugs have
~30% ARR?
Reduction in Annualized Relapse Rate
INF-beta
LFT / CBC / Depression
Copaxone
SC - Glatiramer Acetate - Pregnancy Cat B
Teriflunomide = Aubagio
Oral / BBW - LFT / Enterohepatic recycling
Which MS drugs have
intermediate (47-54%) ARR?
Reduction in Annualized Relapse Rate
- *Tecfidera = Dimethyl Fumurate**
- *53%** - ORAL - PML
Fingolimod = Gilenya
54% - ORAL - PML
contraindicated in CV patients & lot of monitoring
Ocrelizumab = Ocrevus
47% - only drug for PPMS
IV+ needsHEP B
Which MS drugs have
HIGH EFFICACY but pose Significant Risks?
Natalizumab = Tysabri
68% - HIGHEST ARR
But has TOUCH - BBW for PML
Alemtuzumab
49-55% - BBW - cause many issues
Skin Exam / TSH / MALIGNANCIES
Autoimmune disease / Infusion reaction
ADRs & Monitoring
Teriflunomide = Aubagio
“TERRIBLE = TERiflunomide”
- *Severe Liver Injury = BBW**
- *LFTs**
- *Enterohepatic Recycling**
- *Pregnancy Category X –> need to treat for pregnancy**
TB INFECTION
Renal Fxn + CBC + BP
Other ADRs:
ALOPECIA + GI ISSUES + Leukopenia & Lymphopenia
Which MS drug requires a
TB TEST
TERIFLUNOMIDE
Aubagio
TB Test - CBC - Renal Fxn - BP
BBW –> LFT
Pregnancy Cat X - Enterophpatic Recycling
Other ADR:
Alopecia / GI issues / Leukopenia
Dimethyl Fumarate = Tecfidera
ARR% - Indications - MoA
53%
- *RRMS**
- *Oral –> 120 BID f7d –> 240mg BID**
exact MoA is not known
ADR & Monitoring
Dimethyl Fumarate = Tecfidera
has the LEAST ADR
Flushing - GI Problems - ↓Lymphocytes
CBC monitoring
but has:
PML
patients with prolong lymphopenia ( <500 lymph count ) > 6 months
Which MS drug is indicated for:
PRIMARY PROGRESSIVE MS
Ocrelizumab = Ocrevus
47%
RRMS + PPMS
IV Administration
MoA:
humanized MAB –> binds CD20 on B-lymphocytes
Which DMT for MS requires
HEPATITIS B Screening?
OCRELIZUMAB
CD20 - works on PPPMS
HEPATITIS B
need to screen for HBV b4 starting
Significant Infusion RXNs
premedicate with MPD + APAP + Antihistamine
IV administration
Alemtuzumab = Lemtrada
ARR% - Indications - MoA
49-55%
- *RRMS**
- *2+ Inadequate Responses to OTHER DMTs**
- *Only 2 IV infusions in lifetime**
MoA:
MAB –> CD52 on
T + B lymphocytes + monocytes + nK cells
Which DMT drug requires
TSH Test?
Thyroid Cancer / Malignancies
ALEMTUZUMAB
CD52
- *BBW**
- *autoimmune disease** = immune thrombocytopenia
- *infusion rxns** = serious & life threatening
- *MALIGNANCIES** + srs infections
Monitoring
CBC + SCr + UA
TSH / Skin Exam
What MS drugs are
ORAL?
“Oral - DTF”
Dimethyl Fumarate = Tecfidera
Teriflunomide = Aubagio
Fingolimod = Gilenya
What MS drugs are
IV
intravenous
Ocrelizumab
Ocrevus
Natalizumab
Tysabri
Alemtuzumab
lemtrada
