Fingolimod rebound management Tim Soane Neurology Registrar, Forth - - PowerPoint PPT Presentation

Fingolimod rebound management

Tim Soane Neurology Registrar, Forth Valley Royal Hospital

Background

• 45 year old right handed lady
• Physiotherapist
• PMHx Migraines, Depression
• Allergic to sulphonamides
• Lived with husband and 2 children at diagnosis

Diagnosis & Initial Management

• Diagnosed RRMS 2006 one month after initial symptoms
• Was started on Rebif same year
• EDSS 0 but increased to 2 over next 2 years (no details)

Escalation

• 2009. Prolonged relapse with right sided hemiparesis
• Started on Natalizumab

Relapse soon after starting Natalizumab

• 2010. A couple of months after starting Natalizumab

developed left leg weakness

PML derisking

• 2011.

– EDSS 6.0 – JCV positive

• 2012.

– Switched to Fingolimod due to PML concerns, and increasing arthralgias related to infusions

More relapses

• 2012, 2013, 2014 all brought further symptomatic

relapses affecting vision (brainstem), gait and left arm

Alemtuzumab

• 2015 decided to switch to Alemtuzumab
• Approved in 2016
• 10 week washout
• JCV negative CSF
• Within 6 weeks of stopping Fingolimod was admitted to

hospital with leg weakness and incontinence

Evolving high activity

• Admitted to hospital September 2016
• Mixture of evolving CNS inflammation and infections

including UTIs and pneumonia over the following months

• Received in total 3xIVMP and 2xIVIg
• Admitted to ICU November with bulbar dysfunction

MRI Activity

Treatment options

• Initially planned to start Alemtuzumab as in patient, but had

continuing active infections

• Restart Fingolimod, but wasn’t working before
• Switch to Natalizumab, but JCV 2.63, family not keen on PML

risk, and patient never tolerated very well, and still had relapses

• In the end due to ongoing infection given fingolimod via NGT

in ICU

Prolonged hospital admission

• Discharged to rehab, but not home until December 2017

(15 months after admission)

• Zimmer frame with supervision
• Blind in one eye
• Spastic legs requiring baclofen
• RUL ataxia but good LUL
• Cognitive problems

Since discharge

• Slowly improving cognition, but some concerns about

capacity – and declined formal assessment

• Husband died suddenly
• 15 year old son now under care of friends who have

guardianship

• Carers and parents help out but difficult

Current problems

• MRI remains active on fingolimod
• Fingolimod withdrawal previously caused significant

rebound

• High risk of PML
• Cognition and capacity
• EDSS 6.0

Options

• Continue with fingolimod
• Switch to induction agent

– Alemtuzumab

• Escalate

– Natalizumab – Ocrelizumab – Cladribine

• HSCT
• When to give / how to switch

Thank you

• Special thanks to:

– Christian Neumann – Katy Murray – David Hunt