Do you switch Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) patients experiencing a clinical flare?

Switching DMTs After Clinical Flare in Multiple Sclerosis

Yes, you should switch Disease-Modifying Therapies (DMTs) in MS patients experiencing a clinical flare if they are failing their current therapy, as this approach can effectively reduce relapse rates and potentially improve outcomes. 1, 2

Assessment of Disease Activity

When a patient experiences a clinical flare, it's essential to:

• Conduct an MRI to assess new or enlarging lesions using:

  • T2-weighted FLAIR sequences
  • T2-weighted fast/turbo spin echo sequences
  • Gadolinium-enhanced T1-weighted sequences (minimum 5-minute delay after contrast) 3

• Determine if the flare represents treatment failure by evaluating:

  • Frequency and severity of relapses
  • New MRI lesions
  • Progression of disability 1

Decision Algorithm for DMT Switching

1. Confirm treatment failure:

   • Clinical flare despite adherence to current DMT
   • Evidence of new MRI activity
   • Progressive disability

2. Select appropriate second-line therapy:

   • For patients failing first-line injectable therapies (interferons/glatiramer acetate):
     • Consider switching to oral DMTs, which show 95% higher adjusted odds of treatment persistence and 18% lower odds of post-switch relapse compared to switching to another injectable 4
     • High-efficacy therapies (natalizumab, ocrelizumab, ofatumumab) should be considered for highly active MS, as they reduce annual relapse rates by 29-68% 1

3. Monitor response to new therapy:

   • Conduct MRI follow-up at least annually, more frequently (every 3-4 months) for patients at risk of serious treatment-related adverse events 3
   • Assess clinical response through standardized measures (EDSS, MSFC) 1

Evidence Supporting DMT Switching

Research demonstrates that switching DMTs after treatment failure can be beneficial:

• Patients switching from glatiramer acetate to interferon-beta showed significant reduction in annualized relapse rate (ARR) from 0.50 to 0 (p=0.01) 2
• Switching between interferon-beta products resulted in ARR reduction from 0.68 to 0 (p=0.02) 2
• Overall, switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-switch periods 4

Special Considerations

• Safety monitoring: Enhanced pharmacovigilance, including brain MRI every 3-4 months for up to 12 months, is required when switching from natalizumab to other therapeutics (fingolimod, alemtuzumab, dimethyl fumarate) 3

• Progressive MS: For primary progressive MS, ocrelizumab is the only FDA-approved option, reducing clinical progression by 24% versus placebo 1, 5

• JCV status: For patients on natalizumab, JCV antibody status should guide monitoring frequency:

  • JCV positive (high risk): MRI every 3-4 months
  • JCV negative (low risk): Annual MRI 3

Common Pitfalls to Avoid

• Delayed switching: Early identification and treatment during the first 2-10 years of symptom onset is critical to prevent long-term disability 1

• Poor persistence: Only 54.6% of patients remain persistent on second-line therapy throughout the first year 4. Ensure close follow-up and address adherence issues.

• Underestimating subclinical disease: Regular MRI monitoring is recommended even in the absence of clinical symptoms, as subclinical disease activity can lead to worse outcomes 1

• Overlooking carry-over infections: When switching therapies, be aware of potential drug-related adverse effects that can occur at discontinuation or several months after starting a new treatment 3

By following this structured approach to DMT switching after clinical flares, you can optimize treatment outcomes and potentially reduce long-term disability in MS patients.