Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study

Neurology. 2018 May 15;90(20):e1805-e1814. doi: 10.1212/WNL.0000000000005516. Epub 2018 Apr 25.

Abstract

Objective: To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS).

Methods: Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion.

Results: The cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo (p < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing.

Conclusion: Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cells.

Classification of evidence: This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation.

Trial registration: ClinicalTrials.gov NCT01457924.

Publication types

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

MeSH terms

  • Acetaminophen / administration & dosage
  • Administration, Oral
  • Adult
  • Analgesics, Non-Narcotic / administration & dosage
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage*
  • Disability Evaluation
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Histamine Antagonists / administration & dosage
  • Humans
  • Image Processing, Computer-Assisted
  • Injections, Subcutaneous*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Time Factors

Substances

  • Analgesics, Non-Narcotic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Histamine Antagonists
  • Acetaminophen
  • ofatumumab

Associated data

  • ClinicalTrials.gov/NCT01457924