Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study

Mult Scler. 2022 May;28(6):910-924. doi: 10.1177/13524585211044479. Epub 2021 Oct 4.


Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS).

Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion.

Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed.

Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated.

Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

Keywords: Ofatumumab; autoinjector pen; bioequivalence; multiple sclerosis; pharmacokinetics; pre-filled syringe.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Humans
  • Injections, Subcutaneous
  • Multiple Sclerosis* / chemically induced


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • ofatumumab

Associated data

  • ClinicalTrials.gov/NCT03560739