Transitioning immunotherapy in neuromyelitis optica spectrum disorder – when and how to switch

ABSTRACT

Introduction

Newly approved immunotherapies for neuromyelitis optica spectrum disorder (NMOSD) have transformed the treatment landscape and improved disability outcomes. However, there are many remaining questions regarding transitioning immunotherapies in NMOSD that have not been addressed by randomized controlled trials.

Areas covered

This review focuses on the practical questions of managing and switching immunotherapies for NMOSD, including how to transition between immunotherapies, deciding when and if therapy should be discontinued, and transitioning during pregnancy or breastfeeding.

Expert opinion

Clinical experience and retrospective studies of real-world outcomes and complications associated with therapy, as well as therapy transitions, will help inform practice patterns moving forward. Strategies for transitioning between immunotherapies should consider the pharmacokinetics and the onset of clinical efficacy for each drug. Despite all the currently approved preventative immunotherapies, there are limited treatment options for those suffering from significant disability after their initial attack, and remyelination therapies are an important area for future research.

KEYWORDS:

• Discontinuation of therapy
• immunotherapy
• neuromyelitis optica spectrum disorders
• switching
• transitions
• treatment

Article highlights

• Eculizumab, a humanized monoclonal antibody that binds the terminal complement protein C5 and prevents complement activation, has the most rapid onset of action of the newly approved immunotherapies and is useful for immediate control of active disease, including in those who have relapsed while taking other immunotherapies.

• Satralizumab, a humanized monoclonal antibody that acts as an interleukin-6 receptor (IL-6R) antagonist, requires only monthly self-injections and is convenient for long-term use; however, there was a higher risk of early relapses on satralizumab compared to other newly approved immunotherapies.

• Inebilizumab, a humanized, afucosylated IgG1 monoclonal antibody that binds to the B cell surface marker, CD19, and rituximab, a chimeric monoclonal antibody that binds to CD20, are both administered as infusion therapies and are often dosed every 6 months. However, B cell depletion may last a longer or shorter duration.

• All individuals with AQP4 IgG-positive NMOSD should be promptly initiated on immunosuppressive therapy, and there is no safe time to discontinue immunotherapy based on current evidence.

• The pivotal clinical trial for eculizumab allowed for eculizumab treatment 3 months after the last B cell therapy infusion, while the clinical trials for satralizumab allowed for satralizumab administration 6 months after the last B cell therapy infusion. These time periods may guide therapy transitions, although earlier initiation of satralizumab is being investigated and is likely safe.

Declaration of interest

M Levy has received consulting fees from all three manufacturers involved in the trials discussed in this review, Alexion, Viela Bio and Genentech/Roche/Chugai. In addition, he has received consulting fees from Sanofi and UCB Pharmaceuticals. T Kaplan has served on scientific advisory boards for Novartis, Bristol Myers Squibb, and Genentech. 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.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received reimbursement for developing educational presentations, educational and research grants, consultation fees, and/or travel stipends from Biogen, Bayer, Genzyme, Merck, Novartis, Roche, Raffo, and Teva, and have also received grants from LACTRIMS and Guthy Jackson Charitable Foundation. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.