Monoclonal Antibodies in the Treatment of Relapsing Multiple Sclerosis: an Overview with Emphasis on Pregnancy, Vaccination, and Risk Management

Abstract

Monoclonal antibodies have become a mainstay in the treatment of patients with relapsing multiple sclerosis (RMS) and provide some benefit to patients with primary progressive MS. They are highly precise by specifically targeting molecules displayed on cells involved in distinct immune mechanisms of MS pathophysiology. They not only differ in the target antigen they recognize but also by the mode of action that generates their therapeutic effect. Natalizumab, an $$\alpha$$ α 4$$\beta$$ β 1 integrin antagonist, works via binding to cell surface receptors, blocking the interaction with their ligands and, in that way, preventing the migration of leukocytes across the blood–brain barrier. On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. However, potential adverse effects may be serious and can necessitate treatment discontinuation. Most importantly, those are the risk for (opportunistic) infections, but also secondary autoimmune diseases or malignancies. Monoclonal antibodies also carry the risk of infusion/injection-related reactions, primarily in early phases of treatment. By careful patient selection and monitoring during therapy, the occurrence of these potentially serious adverse effects can be minimized. Monoclonal antibodies are characterized by a relatively long pharmacologic half-life and pharmacodynamic effects, which provides advantages such as permitting infrequent dosing, but also creates disadvantages regarding vaccination and family planning. This review presents an overview of currently available monoclonal antibodies for the treatment of RMS, including their mechanism of action, efficacy and safety profile. Furthermore, we provide practical recommendations for risk management, vaccination, and family planning.

A retrospective evaluation of seroconversion after COVID-19 during the early Omicron wave in fully vaccinated multiple sclerosis patients receiving anti-CD20 therapies

“…The immunomodulatory effects of DMTs result in a substantially compromised immune system; the elimination of B-cell populations by anti-CD20 therapies specifically impairs the humoral response to vaccination ( Apostolidis et al, 2021 ; Roach and Cross, 2020 ). Patients with MS and related neuroinflammatory conditions receiving anti-CD20 therapies are at an increased risk of infections and impaired responses to vaccinations ( Bar-Or et al, 2020 ; Krajnc et al, 2022 ). Accordingly, concerns about the implications of limited seroconversion in patients treated with anti-CD20 therapies following COVID-19 vaccination have been reported ( Bar-Or et al, 2020 ; Cross et al, 2022 ; Georgieva et al, 2022 ; Iannetta et al, 2021 ; Levit et al, 2022 ; Smets et al, 2021 ; Tallantyre et al, 2022 ).…”

An Overview of the History, Pathophysiology, and Pharmacological Interventions of Multiple Sclerosis

“…To prevent infusion reactions, patients should be premedicated 30-60 minutes before ocrelizumab infusion with 100 mg of methylprednisolone and antihistamine. Observe patients for 60 minutes after injection of ocrelizumab injection [62][63][64].…”

“…Short-term objectives include reducing MRI lesion activity. Long-term goals involve preventing secondary progressive MS. After beginning the medication, patient compliance and drug toxicity monitoring are the key concerns [ 3 , 62 ].…”

Monoclonal antibody treatment for multiple sclerosis and neuromyelitis optica spectrum disorder: An update

“…The demonstration of the strong efficacy and good safety profile of selective B‐cell‐depleting therapies (such as anti‐CD20 mAbs) has significantly expanded the therapeutic scenario for patients with relapsing and progressive MS with the identification of new therapeutic targets. However, the increased number of treatment options means an added responsibility of completely understanding the characteristics and adverse events of each anti‐mAb treatment before administering it to patients 1,2 …”

“…However, the increased number of treatment options means an added responsibility of completely understanding the characteristics and adverse events of each anti-mAb treatment before administering it to patients. 1,2 The COVID-19 pandemic presents a unique situation where the effects of anti-mAb treatments on COVID-19 and its vaccination should be considered. This poses several questions, such as whether B-cell-depleting options such as rituximab increases the risk of COVID-19 or its severity, if COVID-19 vaccine is effective, and when to initiate anti-mAb treatment.…”