New directions in ocrelizumab therapy in multiple sclerosis: higher doses and subcutaneous therapy

Ocrelizumab is the first anti-CD20 monoclonal antibody approved for the treatment of relapsing and primary progressive multiple sclerosis. Ocrelizumab is administered intravenously (i.v.) at a dose of 600 mg every six months. It is a highly effective drug strongly inhibiting inflammatory changes in the central nervous system, which nearly completely prevents the development of new active magnetic resonance imaging lesions and clinical relapses. Pharmacokinetic studies and data from post hoc analyses of ocrelizumab pivotal studies suggest that a higher dose than the current dose level might have a stronger therapeutic impact. These results revealed that higher ocrelizumab exposure dependent on lower body mass correlated with increased B cell depletion and reduced risk of disability progression independent of relapse activity (PIRA). In addition, higher ocrelizumab exposure showed a correlation with decreased development of new and enlarging T2 magnetic resonance imaging lesions. Two randomised studies are currently under way to compare the efficacy and safety of the standard i.v. dose of 600 mg versus higher doses (1,200 mg or 1,800 mg) in multiple sclerosis patients. Another new direction in the development of ocrelizumab therapy in multiple sclerosis is subcutaneous (s.c.) drug administration. Recent data from the OCARINA study revealed that s.c. ocrelizumab was not inferior to the i.v. administration with respect to pharmacokinetics, magnetic resonance imaging activity, and clinical relapses. The safety of s.c. ocrelizumab was found to be comparable to the i.v. form, with a higher rate of mild local injection reactions.