Subcutaneous Ocrelizumab

The subcutaneous formulation of ocrelizumab is now available on the Pharmaceutical Benefits Scheme (PBS) for relapsing-remitting multiple sclerosis (MS). While the intravenous infusion has been PBS listed since 2018, the subcutaneous option may improve the convenience and accessibility of therapy.

Ocrelizumab is a monoclonal antibody that targets CD20-expressing B cells. It reduces the number and function of these cells which are thought to play an important role in the initiation and progression of MS.

The pivotal OPERA I and OPERA II studies demonstrated the efficacy of ocrelizumab in relapsing MS. Patients were randomly assigned to receive intravenous ocrelizumab every 24 weeks or subcutaneous interferon beta-1a three times a week. The primary end point of annualised relapse rate was 46% and 47% lower for ocrelizumab in the respective studies. Pooled analyses showed a 40% risk reduction for confirmed disability progression at 12 weeks and 24 weeks, and a 33% relative increase in confirmed disability improvement at 12 weeks. The recently published OCARINA II study found subcutaneous ocrelizumab (920mg) to be non-inferior to intravenous ocrelizumab (600mg) for drug exposure, with comparable safety and efficacy.

The usual dose of subcutaneous ocrelizumab is 920mg/23mL injected in the abdomen over ten minutes. The subcutaneous formulation contains the permeation enhancer, vorhyaluronidase alfa. This enzyme hydrolyses hyaluronic acid in the subcutaneous tissue, temporarily increasing tissue permeability and allowing a larger volume to be injected.

Both the intravenous and subcutaneous formulations are administered every six months, although the first intravenous dose is split between two infusions. Premedication with a corticosteroid and an antihistamine reduces the risk of infusion-related reactions. An antipyretic, such as paracetamol, may also be considered.