Ocrelizumab and ofatumumab, but not rituximab, trigger complement induction in vitro

Area of Science:

• Immunology
• Pharmacology
• Neuroimmunology

Background:

• Therapeutic monoclonal antibodies (mAbs) like ocrelizumab, ofatumumab, and rituximab are used for multiple sclerosis (MS).
• These mAbs induce B cell depletion, with complement-dependent cytotoxicity (CDC) as a mechanism.
• Complement activation is implicated in infusion/injection-related adverse reactions for these mAbs.

Purpose of the Study:

• To conduct a head-to-head comparison of complement activation induced by ofatumumab, ocrelizumab, and rituximab.
• To investigate the in vitro complement-activating potential of these anti-CD20 mAbs.

Main Methods:

• In vitro experiments using whole blood from healthy donors.
• Analysis of complement activation after 30-minute exposure to varying concentrations (0.3 mg/mL and 0.9 mg/mL) of the mAbs.
• Measurement of terminal C5b-9 complement complex (TCC) levels as a marker of complement activation.
• Comparison with TNF inhibitory mAbs: adalimumab and infliximab.

Main Results:

• Ofatumumab, ocrelizumab, and infliximab significantly triggered complement activation, indicated by increased TCC levels.
• Rituximab and adalimumab did not induce statistically significant complement activation in this assay.
• Demonstrated distinct complement-inducing potentials among the anti-CD20 mAbs evaluated.

Conclusions:

• Ofatumumab and ocrelizumab exhibit a greater potential to activate complement compared to rituximab.
• These findings provide in vitro evidence for differential complement activation by anti-CD20 mAbs used in MS treatment.
• Results suggest that complement activation potential may contribute to understanding administration-related adverse effects.