MS ECHO: Switching Disease Modifying

Therapies

Gloria von Geldern, MD Assistant Professor Neurology

Conflicts of Interest

Dr. von Geldern has no conflicts of interest to disclose

Objectives

• When to consider switching disease modifying therapies (DMTs)

• Review risks and benefits of switching DMTs

• 49 year old man

• Diagnosed with MS after left-sided numbness and right leg

weakness with typical lesions on MRI brain and C spine

• No other medical problems

• On Copaxone for 7 months: relapse with left leg weakness

• On Rebif for 1.5 years: 4 new lesions MRI brain, no enhancement

• On Tysabri for 4 years: No relapses, MRI stable

• Now: JCV antibody positive

Case

What are reasons to switch DMTs?

• Inadequate adherence to the treatment regimen • Intolerable side effects or laboratory abnormalities • Sub-optimal treatment response

What are reasons to switch DMTs?

• Inadequate adherence to the treatment regimen • Intolerable side effects or laboratory abnormalities • Sub-optimal treatment response

2648 patients on interferons or Copaxone 25% non-compliant (50.2% forgot, 32% injection site reaction)

Devonshire et al. 2010

Predictors of Adherence

2446 patients, at least 12 months - 59.6% adherent • Less likely to have MS-related hospitalization (OR 0.63, 95% CI 0.47–0.83) • Less MS relapses (OR 0.71, 95% CI 0.59–0.85 • Lower medical costs ($3380 vs. $4348, p=0.003)

Tan et al. 2010

Adherence is Associated with Lower Medical Cost

What are reasons to switch DMTs?

• Inadequate adherence to the treatment regimen • Intolerable side effects or laboratory abnormalities • Sub-optimal treatment response

Coyle, 2013

What are reasons to switch DMTs?

• Inadequate adherence to the treatment regimen • Intolerable side effects or laboratory abnormalities • Sub-optimal treatment response

Coyle, 2013

Breakthrough Disease Activity

No evidence of disease activity (NEDA)

- No relapse

- No worsening of disability (EDSS)

- No new, enlarging or enhancing lesion on MRI

In clinical trials less than 50% of patients

have NEDA over 2 years

What is a realistic goal?

Gajofatto et al. 2009

Rio et al. 2012

Kalincik et al. 2015

• Choice of new DMT depends on reason for switch DMT with different mechanism of action • Consider what tests you need before switching • Decide on wash-out period

How to switch DMTs

Washout

• Period between stopping old and starting a new DMT

• Minimize esp if patient has aggressive disease

• Optimal wash-out period depends on

- pharmacodynamics of old and new DMT

- possible laboratory abnormalities

Washout

• Typically no wash-out needed coming off GA or IFNβ

• Tysabri to Gilenya: ideally <2 months

• Tysabri to Copaxone: may need to overlap?

Jokubaitis et al. 2014

Resources • Consensus on Disease-Modifying Therapies

– Summary version may be useful when discussing treatment options with patients and advocating with insurers for access and coverage.

• Changing Therapy in Relapsing Multiple Sclerosis: Considerations and Recommendations of a Task Force of the National Multiple Sclerosis Society

• MS Navigator (1-800-FIGHT MS), Society Patient Packets