This document discusses guidelines for stopping disease-modifying therapies (DMTs) in multiple sclerosis (MS) patients. It notes that the decision to stop should consider factors like type of MS, disability level, duration of remission, and age. Older patients and those with longer remission periods are less likely to see returns of disease activity after stopping. It also warns that certain DMTs like natalizumab have higher risks of rebound disease activity. The document advocates discussing potential DMT stops before starting treatment and promoting education to help patients make informed decisions.

1. A PRACTICAL GUIDE TO STOPPING
DISEASE MODIFYING THERAPY
Charles Hillier
Michelle Davies
Cheryl King
On behalf of the Dorset MS service
November 2019

2. Disclosure of interest
The Dorset MS service has received lovely sandwiches’ (mainly from M&S)
from all good pharmaceutical companies involved in MS and loves twinkly
things, nice pens and misses post-it notes. We have been taken on nights out
for dinner and some of us funded to go to conferences all expenses paid (more
please). We will never knowingly obstruct a DMT prescription if the
pharmaceutical sales person is nice to us and it helps if they are good looking.
We miss the old days of unrestricted budgets to entertain us and we are sure
that we have been unbiased in our prescribing habits, but recognise that if
pharmaceutical companies do not make vast profits there will be no new drugs
for MS.

4. ‘I want to break free from DMTs’
• Any evidence to guide us on who and when to stop?
• When to have the conversation
• The practical bit
• Group discussion Q and As
• Summary

5. Questions:
• When should we stopping DMTs?
• no longer effective
• causing harm – side effects
• both
• What factors influence your decision?
• type of MS
• level of disability
• length of time with MS and relapse freedom
• age
• What monitoring should take place after the decision to stop?

6. What image do you have of the person with
MS who should consider stopping DMTs ?

9. Long term side effects: IFNs Reder MSARD 2014

10. Long term side effects: IFN and others
• Infection
• PML
• Cancer
• Hypertension
• Long term SE of newer DMTs just not known

11. Outcomes in stable MS after stopping DMT
• Comparison of DMT “stoppers” (485) vs DMT “stayers (854)” MS base
• treated > 3 years with injection DMTs, mean age 45
• no relapses > 5 years
• FU > 3 years
• Key findings:
• Relapse rate the same in the two groups (25%)
• As you get older relapse rate reduced
• Disability progression did occur sooner in the ‘stoppers’
Krister JNNP 2016

12. Factors influencing return of disease activity
• N = 4842
• Kister J Neurol Sci 2018
• Guess what?
• Older you are less likely to relapse or progress
• Lack of disease activity before stopping also predicts return of disease activity
• the longer you are relapse free before stopping the less likely you will relapse
or progress on stopping

13. Treatment effect in part age related
Inhibitionofdisabilityprogression(%)

14. Stopping DMTs in non relapsing MS
• Increasing age
• Stability
• Birnbaum Int J MS Care 2017

15. Stopping DMTs all the same ? NO
NTZ n =15 1st Line n = 55 Fagius MSARD
2017

16. Rebound with Natalizumab (NTZ)
N=142 switch
NTZ to fingolimod
(TOFINGO)
Different washout periods
return of activity from 12
weeks.
Kappos Neurology 2015

17. Stopping NTZ and return of disease activity
• RESTORE (1:1:2)
• N=175
• Stable disease
• Either:
• Continue (n = 45)
• Stop (n = 42)
• GA , interferon, MP (n = 88)
• Activity return from 4 weeks
Fox Neurology 2014

20. Fingolimod: rebound syndrome
Up to 11% 4 -16 weeks after stopping Hatcher jama neurol 2016 and others

21. Infographic summarising advice about the use of disease-modifying drugs during pregnancy
and in breastfeeding.
Ruth Dobson et al. Pract Neurol 2019;19:106-114
©2019 by BMJ Publishing Group Ltd

22. ARCHIE 2 years 8 months taken 21/10/19 in his new coat 😄
KENZIE 4 years 5 months. I have just started
school and I am going to be a Big Brother in 6
months.
ALEXANDER 6 months. My Mummy stopped Fingolimod Smarties to have my Big Sister Poppy.
Mummy got poorly after Poppy was born so Dr Hillier gave her Tysabri juice and she made me.

23. What do we do?
• Talk about stopping DMTs before starting DMTs
• Encourage women of child bearing age to think carefully before starting
fingolimod, DMF and Teriflunomide
• SPMS Interferons age > 55 Offer baseline scan before stopping
• Offer a ‘drug holiday’
• Those on NTZ switch to Fingo and continue for at least 2 years
• Promise continued follow up with same team and same members of the team

24. Principles to guide practice (Hua)
• Current DMTs benefits appear to reduce as inflammation naturally wanes
• Around age 60
• DMT is not without risk
• Other factors
• Stable with mild disability for several years
• Severe progressive disability despite DMT
• Cost

25. What have we learnt?
• Stable disease and age > 55: consider having the conversation
• Progression, Infection, EDSS 7 : consider having the conversation
• Watch out, watch out : rebound about
• Pregnancy: safe to continue GA and IFN
Consider continuing NTZ

27. Future Evidence: DISCO-MS trial
• US based
• RCCT
• Stable MS 5 years (RRMS or PMS)
• Age >55
• 2 years
• % new relapse / MRI activity
• % with EDSS change
• Patient reported outcome
• 250 recruited as July 19

28. Dorset MS Service – Continuing the legacy
The process that Dorset MS Service follows in terms of DMD is still based on
what the service did when it was set up in 2003
This is due to the benefits the service has found in terms of compliance and the
relationship with the pwMS

29. Juggling within existing resources
• Choices of Dorset MS Service:
• To invest in DMD counselling & education
• Improved compliance
• Reduced Rx switches
• Dorset MS Service does all counselling and follow-up
• Named practitioner for all patients
• Practitioner knows pwMS well
• Improved patient knowledge leads to improved response to changes (DMD or other)
• Reduction in time for DMD clinics
• Unable to do holistic MS review annually for all DMD patients
• Increase in DMD work has knock on effect on non-DMD caseload
• Business Cases
• To highlight capacity issues & provide data to support increase in staff

30. DMD Counselling
• Broad education
• 60-90 minutes
• Group/1:1
• Includes expectations for pwMS continuing on treatment with knowledge of expected side
effects
• Includes stopping criteria
• DMD specific Education
• Group/1:1
• 60 minutes
• Injectables - First injection at Poole Hospital
• Follow-up phone call day after starting treatment