mutiple sclerosis practice guidelines

1. MS PRACTICE GUIDELINES
Dr prashant shringi
AAN recommendations April 23, 2018
ECTRIMS/EAN Guideline on the pharmacological treatment of people
with multiple sclerosis2017

2. 1. When to start treatment? –DMT Various subtypes of
MS,CIS, RIS
2. Monitoring treatment ?
3. when to switch-DMT?
4. Acute & symptomatic T/t
5. when to stop?
6. Add on drugs or second line drugs for inadequate
response or frequent relapses?
7. Special situations –childhood MS,pregnancy,elderly
8. monitoring of individual drug
9. Follow up

3. Q1.When to start treatment? –DMT for Various
subtypes of MS,CIS, RIS
• Clinically isolated syndrome(CIS)
• No / yes
• Serial imaging at least annually for the first five years and
close follow-up rather than initiating DMT in people with CIS
• Offer IFN or glatiramer to patients with CIS and an abnormal
MRI with lesions suggestive of MS who do not fulfil criteria
for MS (EAN)
• First clinical episode ,an event or precedent history that is
suggestive of demyelination lasts at least 24hrs and occurs in
the absence of fever, infection or encephalopathy

4. • Radiologicallyisolated sydrome(RIS)
• No
• 34% of patients with RIS develop a first acute clinical event
consistent with CIS within 5 years
• Incidental brain or spinal cord MRI findings that are highly
suggestive of MS in an asymptomatic patient lacking any
history ,symptoms or signs of multiple sclerosis

5. DMT for MS
• When to start for MS-
 fulfilling criteria for MS(Revised Mcdonald’s criteria ,
MAGNIMS 2016 criteria)
 Active lesion on MRI- evidence of inflammation
 After discussing the risks and benefits, DMT should be
prescribed to people with a single clinical demyelinating event
and ≥2 brain lesions characteristic of MS who decide they
want this therapy
 should offer DMTs to people with relapsing forms of MS with
recent clinical relapses or MRI activity

6. Not to start DMT
• Serial imaging at least annually for the first five years and
close follow-up rather than initiating DMT in people with-
 no relapses in the last two years,
 no active new MRI lesion

7. Which DMT should start ?
• ascertain preferences in terms of safety, route of
administration, lifestyle, cost, efficacy, AEs and tolerability in
the choice of DMT- pt choice
• DMTs are prescribed to reduce relapses and new MRI lesion
activity and not for symptom improvement in people with MS
• Started with –
• INF
• glatemir

8. • Highly active MS - prescribe alemtuzumab, fingolimod, or
natalizumab
• In pt of MS who are candidates for DMTs who do not have access
to approved DMTs azathioprine or cladribine should started
• Mitoxantrone- Because of the high frequency of severe AEs,
clinicians should not prescribe to people with MS unless the
potential therapeutic benefits greatly outweigh the risks

9. • SPMS
• First rule out other causes of progressive disability in MS-
• Mitoxantrone –FDA approved
• High dose interferon beta
• Almetuzumab
• Cyclophosphamide
• Cladrbinre
• Rituximab ???
• Pulse steroids NO
• Ivig

11. • PPMS
• should offer ocrelizumab to people with PPMS who
are ambulatory
• March 2017
• Anti-CD20 mab designed to optomize cell depletion
 300mg infusion given 14 days apart(total-600mg) for
atleast 120 weeks
 C/I in hepatitis B infection

12. Monitoring treatment ?
Assesment efficacy of treament
• Consider combining MRI with clinical measures when
evaluating disease evolution in treated patients
• When monitoring treatment response in patients
treated with DMDs, perform a reference brain MRI
usually within 6 months of treatment onset and
compare it with a further brain MRI performed
typically 12 months after starting treatment

13. • When monitoring treatment response,
measurement of new or unequivocally enlarging
T2 lesions is the preferred MRI method
supplemented by GAD enhancing lesions for
monitoring treatment response
When monitoring treatment safety, perform brain MRI yearly
in low risk and 3-6 monthly in high risk PML patients

14. Add on drugs or second line drugs for inadequate
response or frequent relapses?

15. when consider to switch-DMT?
• In following condition one can swtich DMT-
• 1. When any pt using a DMT long enough for the
treatment to take full effect and are adherent to
their therapy when they experience-
one or more relapses
two or more unequivocally new MRI-detected lesions
increased disability on examination, over a one-year period of
using a DMT

16. when consider to switch-DMT?
1. change to noninjectable or less frequently injectable DMTs
who report intolerable discomfort with the injections or in
those who report injection fatigue on injectable DMTs
2. switch DMT or reducing dosage or frequency when there are
persistent laboratory abnormalities
3. If a patient develops malignancy or oppurtunistic infection
while using a DMT
4. Natalizumab- -pt who have infusion reactions and who
experience breakthrough disease activity - should switch
DMTs if they have persistent antibodies, check natalizumab
antibodies

17. when consider to switch-DMT?
• Physician -counsel people considering natalizumab
discontinuation that there is an increased risk of MS relapse
within six months of discontinuation Level A
• initiate treatment(fingolimod, rituximab) within eight to 12
weeks after natalizumab discontinuation

18. When to stop DMT in MS pt ?
1. Pregnancy
2. Trial off therapy- stable MS
3. SPMS-pt who do not have ongoing relapses (or
gadolinium-enhanced lesions on MRI activity) and
have not been ambulatory (EDSS 7 or greater) for at
least two years. Level C
4. CIS- Clinicians should review the associated risks of
continuing DMTs versus those of stopping DMTs
LevelB

19. Acute & symptomatic T/t
• Treatment of acute relapse
 IV methylprednisolone (first line therapy)
 Plasma exchange (second line therapy)
• 5-7 exchanges recommeded on every 2 days, 30-
50ml/kgw
Who do not respond to glucocorticoids

20.  Cognitive impairment-DMT
 Depression-Duloxetine,escitalopram
 Fatigue:Amantidine,Modafinil,Dextroamphetamine,methylpheni
 Gait impairment:Dalfampridine (K channel blocker) 10 mg bd,
• C/I-if seizure history
 Heat intolerance-Dalfampridine
 Paroxysmal symptoms- Carbamazepine(CBZ)
 Lhermitte sign-gabapentin,pregaba,CBZ
 Spasticity- Tizantidine, baclofen, dantrolone, clonezepam

21. Special situations
• Pregnancy –
• All DMTs are not licensed during pregnancy, except
glatiramer,INF
• counsel women to stop their DMT before conception for
planned pregnancies and should not initiate DMTs during
pregnancy unless the risk of MS activity during pregnancy
outweighs the risk associated with the specific DMT during
pregnancy
• Pregnancy – immunomodulatory effect on MS – decreased
relapse rate

22. • EAN
women with persistent high disease activity, advise to delay
pregnancy. If despite this advice, still decide to become
pregnant:
 treatment with natalizumab throughout pregnancy may be
considered
 treatment with alemtuzumab could be an alternative,
provided that a 4-month interval is strictly observed from the
latest infusion until conception

23. • Breast feeding – DMT should be Stop
• OCP- can be used in MS
• Some studies- OCP reduced relapse

24. • Chidhood MS:
• 6-18% before 18 yr
• First symptom ADEM like presentation –relapse-MS
• Female=male
• Nearly always RRMS type
• Relapse rate is more than adults
• Prognosis is good than adult MS
• Treatment – same as adult MS

25. Dose & monitoring of individual drug
• INF:
• Interferon beta-1b 8 mIU subcutaneous alternate day
• Interferon beta-1a 30 micrograms IM weekly
• Interferon beta-1a 44 micrograms subcutaneous 3 times per
week
• A/E: Postinjection flulike symptoms Depression, suicidal
ideation, or psychosis. Hepatic injury, Anaphylaxis, Decreased
peripheral blood counts
• Monitoring : CBC, LFT

26. • Glatiramer Acetate:
• 40 mg SQ injection TIW
• A/E: Lipoatrophy and skin necrosis,Postinjection reaction -
flushing, chest pain, palpitations, anxiety, dyspnea, throat
constriction, or urticaria
• No laboratory monitoring is neccessary
• Natalizumab: infusion
• 300 mg IV over one h every 4 wk
• A/E: Anaphylaxis .Risk of PML.Herpes encephalitis or
meningitis,Hepatotoxicity
• Monitoring : JC virus ab in every months

27. • Fingolimod:oral 0.5mg/day
• A/E: bradycardia, herpesvirus infections, basal cell skin cancer,
macular edema, and abnormal pulmonary function test
• Monitoring : CBC, pre-screening for VZV immunity, ophthalmologic
evaluation to screen for macular edema, and ECG testing to rule out
cardiac conduction abnormalities
Teriflunomide:7 or 14 mg RRMS
A/E :Increased blood pressure,Alopecia, nHeadache, Diarrhea, Severe
liver injury.
Monitoring: patients should be screened for latent tuberculosis and
women of childbearing potential should undergo pregnancy testing.
Liver function tests should be obtained monthly during the first 6
months of treatment, and intermittently thereafter.

28. • Dimethyl fumarate
• 240 mg BD/TDS
• A/E:lymphopenia , Flushing, abdominal pain, and diarrhea,
Angioedema and anaphylaxis
• Monitoring :CBC

31. Follow up
Clinical follow up –acute attacks
Cognitive assessment
EDSS every 3 months
MRI every 12 months
Modified Rio score

34. Newer therapeutic agents
S1P Receptor Modulators
Siponimod ,ozanimod
Anti-LINGO ab: opicinumab
Idebenone
 MIS416
Ofatumumab:anti CD 20 antibody

35. • Risk of developing PML in JC ab negative pt on
natalizumab ?
• 10-20% annualy
• 2-3% annualy
• 50% annualy
• No risk

36. • Which drug not required laboratory
montoring?
• Teriflunamide
• Inf
• Glatemir
• Alemetezumab

37. • Highly active MS which drug is beneficial?
• Inf
• Azathipirone
• Fingolimod
• Glatemir

38. • 40 year old female develpoed one attack of
MS started on DMT improved developed 2
attack after 1 year than DMT switched but her
weakness worsen continiously , CONTRAST
MRI showed no new lesions what next?
• Add 2 line drug
• Continue same DMT
• Start ocrelizumab
• Nothing

39. • Thank you