B cell depletion in the treatment of multiple sclerosis

ABSTRACT

Introduction: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The latest development of B-cell depletion by anti-CD20 monoclonal antibodies has been a large step forward in the treatment of this devastating disease.

Areas covered: In this manuscript, we review mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab.

Expert opinion: B-cell depletion efficiently suppresses acute inflammatory disease activity in relapsing-remitting MS (RRMS), and may slowdown progression in primary progressive MS (PPMS). The treatment is generally well tolerated, with manageable adverse events related to infusion reactions and infections. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, is the first therapy to be approved for the treatment of both RRMS and PPMS.

KEYWORDS:

• Multiple sclerosis
• B cell
• anti-CD20 antibody
• rituximab
• ocrelizumab
• ofatumumab
• treatment

Article highlights

• Based on phase-III RCTs, ocrelizumab is approved for the treatment of RRMS and PPMS, and ofatumumab is currently investigated in phase-III RCTs in RRMS.

• Early phase II/III RCTs and increasing evidence from real would experience indicate effect from rituximab therapy in RRMS and PPMS, similar to ocrelizumab

• B-cell depletion, by ocrelizumab, ofatumumab, and rituximab, efficiently suppresses acute inflammatory disease activity in relapsing-remitting MS (RRMS)

• B-cell depletion, by ocrelizumab and rituximab, may slowdown progression in primary progressive MS (PPMS) – but with probably best effect in patients with signs of inflammatory disease activity.

• B-cell depletion is generally well tolerated in MS, with manageable adverse events related to infusion reactions and infections.

• More data on long-term efficacy and safety is still needed for the B-cell depletion therapies in both RRMS and PPMS.

This box summarizes key points contained in the article.

Declaration of interest

K M Myhr has received unrestricted research grants to his institution and/or scientific advisory board or speakers honoraria from Almirall, Biogen, Genzyme, Merck, Novartis, Roche and Teva; and has participated in clinical trials organized by Biogen, Merck, Novartis, and Roche. Ø Torkildsen has received unrestricted research grants to his institution and/or scientific advisory board or speaker honoraria, or travel grants from Biogen, Genzyme, Merck, Novartis and Roche, and has participated in clinical trials organized by Genzyme, Merck, Novartis, and Roche. A Lossius has received speaker honoraria from Roche, and unrestricted research grants from Sanofi Genzyme. L Bø has received unrestricted research grants to his institution and/or scientific advisory board or speakers honoraria from Biogen, Genzyme, Merck, Novartis, Roche and Teva; and has participated in clinical trials organized by Biogen, Merck, Novartis, and Roche. T Holmøy has received unrestricted research grants to his institution and/or scientific advisory board or speakers honoraria from Biogen, Genzyme, Merck, Novartis, Roche, Santen and Teva; and has participated in clinical trials organized by Biogen, Merck and Roche The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Review Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.