When to stop Ocrevus (ocrelizumab) in patients with Primary Progressive Multiple Sclerosis (PPMS)?

When to Stop Ocrevus in PPMS

Ocrevus (ocrelizumab) should be continued indefinitely in patients with Primary Progressive Multiple Sclerosis (PPMS) who are tolerating the medication well, as there is no established protocol for discontinuation and stopping therapy may lead to disease reactivation and progression.

Rationale for Continued Treatment

Ocrevus is the only FDA-approved disease-modifying therapy for PPMS, and long-term data supports its continued use:

• The ORATORIO trial and its open-label extension demonstrated that patients who received continuous ocrelizumab treatment had significantly lower rates of disability progression compared to those who switched from placebo (51.7% vs 64.8% for EDSS progression) 1
• Early and continuous ocrelizumab treatment provided sustained benefits on measures of disease progression over 6.5 years of follow-up 1
• Patients who discontinued ocrelizumab showed higher rates of disease progression than those who maintained therapy 1

Situations When Discontinuation May Be Considered

Despite the general recommendation for continued treatment, there are specific circumstances when stopping Ocrevus should be considered:

1. Disease Progression Despite Treatment

   • Continued rapid disability progression despite at least 1-2 years of treatment
   • Development of wheelchair dependency (EDSS ≥7) with no signs of benefit

2. Safety Concerns

   • Life-threatening infusion reactions 2
   • Active hepatitis B virus infection 2
   • Serious infections that are recurrent or difficult to manage
   • Development of progressive multifocal leukoencephalopathy (PML)

3. Patient Factors

   • Advanced age with significant comorbidities where risks outweigh benefits
   • Patient preference after thorough discussion of risks/benefits

Monitoring for Treatment Response

Regular monitoring is essential to evaluate treatment response and guide decisions about continuation:

• Clinical assessments every 3-6 months to evaluate disability progression
• MRI scans annually to assess new or enlarging T2 lesions and T1 hypointense lesions
• Assessment of patient-reported outcomes and quality of life measures

Special Considerations

Pregnancy Planning

If a female patient is planning pregnancy, Ocrevus should be discontinued:

• Last dose should be at least 6 months before conception due to the long B-cell depletion effect
• Treatment can be resumed after delivery and completion of breastfeeding if desired

Vaccination Timing

For patients requiring live or live-attenuated vaccines:

• Consider temporary interruption of Ocrevus
• MS patients receiving ocrelizumab can receive non-live vaccines 4-6 weeks before starting treatment or 4-6 months after the last dose 3

Rebound Risk

A critical consideration when stopping Ocrevus is the risk of rebound disease activity:

• Evidence from other B-cell depleting therapies suggests that abrupt discontinuation may lead to return of disease activity
• If discontinuation is necessary, close monitoring for disease reactivation is essential
• Consider overlapping with another disease-modifying therapy if Ocrevus is being discontinued due to inadequate efficacy

Conclusion

The decision to stop Ocrevus in PPMS should be approached with caution given the lack of alternative approved therapies and evidence showing benefits of continuous treatment. Regular monitoring of disease activity, disability progression, and safety parameters should guide treatment decisions.