Extended Interval Dosing of Ocrelizumab Prevents Immunoglobulin Drop in MS

In patients with multiple sclerosis (MS) who achieved stable disease with ocrelizumab, extended interval dosing prevented the decline of immunoglobulin levels and was associated with continued stable disease. Researchers published results from their pilot study online ahead of print in Med.

“Long-term B cell depletion with ocrelizumab in MS is associated with severe side effects such as hypogammaglobulinemia and infections,” wrote a research team from the University Medical Center of the Johannes Gutenberg University Mainz in Germany. “Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing scheme.”

The study included 51 patients with at least 2 years of treatment with ocrelizumab. After 4 or more treatment cycles, 14 patients chose to continue the standard interval dosing regimen. Twelve other patients with clinically and radiologically stable disease switched to B cell-adapted extended interval dosing, in which the next dose occurred when CD19+ B cells were greater than 1% of peripheral blood lymphocytes.

Under ocrelizumab treatment, patients’ immunoglobulin M levels declined rapidly, according to the study. Patients with lower levels of immunoglobulin at baseline and more previous disease-modifying therapies were at higher risk for hypogammaglobulinemia.

Under B cell-adapted extended interval dosing of ocrelizumab, the average time to next infusion lengthened from 27.3 to 46.1 weeks, the study found. Patients in the standard interval dosing group showed a significant drop in immunoglobulin levels over 12 months, but those in the extended interval dosing group did not.

Under extended interval dosing, patients remained stable on a slew of assessments, including the  Expanded Disability Status Scale, neurofilament light chain, timed 25-foot walk, 9-hole peg test, Symbol Digit Modalities Test, and Multiple Sclerosis Impact Scale (MSIS-29), researchers advised.

“Based on these findings,” they wrote, “we propose a new algorithm for long-term ocrelizumab treatment.”

Reference: 
Schuckmann A, Steffen F, Zipp F, Bittner S, Pape K. Impact of extended interval dosing of ocrelizumab on immunoglobulin levels in multiple sclerosis. Med. Published online May 21, 2023. doi:10.1016/j.medj.2023.05.001