Background

Ocrelizumab is one of the most effective disease-modifying drugs for MS. As a potent immunosuppressor, ocrelizumab carries significant infection risk and its long-term effects on immunocompetence are not fully understood. Although ocrelizumab is given as a regular six-monthly infusion, it shares several characteristics with immune reconstitution therapies, such as alemtuzumab and cladribine. Alemtuzumab and cladribine deplete circulating lymphocytes and ocrelizumab specifically depletes circulating B-cells, with reconstitution of cells occurring from bone marrow. It is not known whether the therapeutic effect of ocrelizumab outlasts the administration period. Giving ocrelizumab in a time-limited fashion could reduce both short- and long-term side effects, as well as provide a substantial cost reduction.

Objectives

Share experience of a case in order to stimulate investigation into ocrelizumab as an immune reconstitution therapy.

Methods

1. Consent was successfully obtained to present the patient's case.

2. Case details were collated, including radiological and laboratory data.

Results

A 24-year-old female patient was diagnosed with MS following subacute onset left hemiparesis, positive CSF oligoclonal bands, exclusion of mimics and MRI showing multiple T2 lesions in the periventricular areas, corpus callosum and juxtacortical areas. Her baseline MRI performed immediately prior to treatment commencement showed five new T2 lesions with new enhancement. She was treated with five doses of ocrelizumab at six-monthly intervals between 2012-14 as part of a clinical trial. She then decided to withdraw from the study to travel, but returned to the UK in 2020. Despite cessation of all disease modifying treatment for six years the patient reported no clinical relapses, and in comparison with the MRI at treatment cessation in 2014 there were no new lesions or enhancement. Lymphocyte subset analysis showed reconstitution of B-cells (578 x 10⁶ cells/L; normal range 50-500 x 10⁶ cells/L). The patient is fit and well and suffered no side effects of treatment.

Conclusions

A patient treated early with a limited course of ocrelizumab for two years demonstrated no evidence of disease activity (NEDA2) after six years without treatment. Caution is recommended in extrapolation from a single case, however investigation of ocrelizumab as an immune reconstitution therapy is warranted. Limited duration ocrelizumab treatment could have substantial benefits in terms of side effects, cost and patient convenience whilst maintaining efficacy.