To evaluate the onset of ofatumumab 20 mg subcutaneous (s.c) effect on B-cell depletion and suppression of magnetic resonance imaging (MRI) activity in relapsing multiple sclerosis (RMS) patients.

B cells play a major role in the pathogenesis of MS. Ofatumumab, the first fully human
anti-CD20 monoclonal antibody with a monthly 20 mg s.c. dosing regimen suppressed 94–98% of the gadolinium-enhancing (Gd+) lesions versus teriflunomide in the Phase 3 ASCLEPIOS I/II trials. In APLIOS, with monthly MRI scans, the onset of ofatumumab action on B-cell depletion and MRI activity suppression can be determined.

APLIOS was a 12-week, open-label, bioequivalence Phase 2 study in typical RMS patients (N=284) who received an initial loading dose of ofatumumab 20 mg (0.4 mL) s.c. (initial loading dose on Days 1, 7, and 14, and maintenance dose every 4 weeks from Week 4 onwards) via autoinjector or prefilled syringe. Depletion of CD19+ B cells was measured before administration of every new injection. Gd+ lesion counts at baseline and at Weeks 4, 8, 12 were assessed.

The loading doses of ofatumumab depleted B cells rapidly; the proportion of patients with B-cell concentrations of <10 cells/µL was >65% after the first injection by Day 7, 94% by Week 4, and sustained >95% at all following injections. Ofatumumab treatment reduced the mean number of Gd+ lesions from baseline (1.5) to 0.8, 0.3, and 0.1 by Weeks 4, 8, and 12, respectively; the proportion of patients free from Gd+ lesions at the corresponding time points were 66.5%, 86.7%, and 94.1%, respectively.