Fewer Infusions, Same Protection? Rethinking Ocrelizumab Dosing in Multiple Sclerosis
Ocrelizumab has transformed how we treat multiple sclerosis (MS). By depleting B cells, it can dramatically reduce relapses and slow disease progression. But like many powerful therapies, it comes with a trade-off: long-term risks, including declining antibody levels (hypogammaglobulinemia), higher infection rates, and weaker vaccine responses.
A study by Schuckmann and colleagues, published in Med (2023), asks an important question: Do patients really need ocrelizumab infusions every six months—or could many safely extend the interval between doses?
Why Rethink the Dosing Schedule?
The standard protocol for ocrelizumab is an infusion every 24 weeks. But research shows only about 3–5% of patients actually see their B cells return within that window. This means the majority are receiving treatment while their immune cells are still suppressed. That might be unnecessary, and potentially harmful.
The COVID-19 pandemic highlighted this issue. Many patients had delayed infusions due to lockdowns, yet most remained stable. This opened the door for systematic testing of extended interval dosing (EID)—a strategy where treatment timing is guided by each patient’s B cell recovery, rather than a rigid calendar.
The Study at a Glance
Who was studied?
51 MS patients treated with ocrelizumab for at least 24 months.
What happened?
After four infusion cycles, patients either:
Stayed on standard interval dosing (SID) every 6 months (14 patients), or
Switched to extended interval dosing (EID) if their disease was stable (12 patients). In EID, the next infusion was given only when B cells (CD19+) rose above 1% of lymphocytes—though never earlier than 6 months.
Key measures:
Immunoglobulin (antibody) levels (IgG, IgM, IgA)
MS disease activity (relapses, MRI, disability scale, functional tests)
Blood biomarkers of nerve damage (neurofilament light chain, NfL)
Treatment cost
What They Found
Antibodies Decline with Standard Dosing—but Not Extended
IgM dropped rapidly in all patients during the first two years of ocrelizumab.
Under continued SID, IgG, IgM, and IgA all kept declining.
With EID, antibody levels stabilized—suggesting less impact on immune resilience.
Disease Control Was Just as Strong
Patients on EID remained clinically and radiologically stable, with no new relapses.
Disability scores (EDSS), walking and hand function tests, and cognitive measures all showed no worsening.
NfL levels—indicating nerve damage—were equally low in both groups.
Individual Risk Factors Matter
Patients with lower baseline immunoglobulin levels and more prior MS therapies were at higher risk for hypogammaglobulinemia.
This points to the need for personalized monitoring when tailoring treatment schedules.
Economic Impact
Extending intervals reduced the average time between infusions from 27 to 46 weeks.
That translated into a 36% cost reduction—over €11,500 saved per patient per year in Germany.
Why This Matters
The results suggest that for stable patients, less can be more: fewer infusions, fewer risks, lower costs—and no loss in efficacy.
For patients: Extending the interval may preserve immune defenses and improve responses to vaccines (a critical issue in the era of COVID-19).
For clinicians: Monitoring B cells instead of defaulting to fixed schedules allows for individualized care.
For health systems: The cost savings could be substantial, freeing resources for wider patient access.
Caveats and Next Steps
This was a pilot study, with only 26 patients in the dosing comparison and one year of follow-up. Larger, randomized clinical trials are needed before guidelines can officially change. Also, the study mostly included stable patients—those with active disease may still require standard dosing.
A Shift Toward Personalized MS Care
The takeaway? Extended interval dosing of ocrelizumab shows promise as a safer, more efficient, and cost-conscious strategy—at least for patients who are stable on therapy.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Schuckmann, A., Steffen, F., Zipp, F., Bittner, S., & Pape, K. (2023). Impact of extended interval dosing of ocrelizumab on immunoglobulin levels in multiple sclerosis. Med, 4(6), 361-372.
