Advances in preventing adverse events during monoclonal antibody management of multiple sclerosis

ABSTRACT

Introduction: Decades of pharmacological research in Multiple Sclerosis (MS) led to the development of therapeutic Monoclonal Antibodies (MAbs) with many different mechanisms of action (MoA), potentially able to improve disability outcome but also determining a more complex management of patients.

Areas covered: When clinicians select MS treatments, they should consider adverse events (AEs) on individual basis to minimize patients’ risks. Some AEs are common and can be easily handled, but rare complications should also be taken into account. The aim of this review is to summarize existing evidence and provide practical recommendations for the management of therapeutic MAbs in MS.

Expert opinion: The introduction of MAbs revolutionized MS treatment with an improvement in effectiveness. Unfortunately, this has been coupled with a more complex array of AEs needing a tighter surveillance strategy. A close interaction between general practitioners, neurologists, and other specialists is the key for a safer use of such effective drugs.

KEYWORDS:

• Monoclonal antibodies
• multiple sclerosis
• disease-modifying therapies
• natalizumab
• alemtuzumab
• ocrelizumab

Article highlights

• Monoclonal antibodies (MAbs) are the most efficacious disease-modifying therapies (DMTs) for MS with a high rate of reduction of clinical relapses and MRI activity.

• The administration of MAbs must be initiated and continuously supervised by specialized physicians and resources for the management of hypersensitivity reactions should be available during the infusions.

• Serious infections represent rare events; however, a potentially serious infectious event or an opportunistic infection should be always considered in symptomatic patients.

• Before the administration of MAbs, patients must be tested for hepatitis B and C, VZV, HIV, and latent tuberculosis.

• A test for JCV antibodies should be performed before treatment with NTZ to quantify the specific risk of PML. The test should be repeated at different set times depending on their anti-JCV serological status, and the patients must follow MRI monitoring.

• Dietary restriction for the prevention of Listeriosis and treatment with antiviral drugs for the prevention of herpes infections are required for therapy with ALZ

• Regular blood testing for hematology, kidney and thyroid functions as well as regular urinalysis can early identify autoimmune reactions related to ALZ.

• Is too early to drawn definitive conclusion about cancer risks, individual risk should be evaluated and the surveillance plan recommended for general population can be intensified on individual basis. HPV DNA test is required before administration of ALZ in order to reduce the risk of uterine cervix cancer.

• Pregnancy should be discussed before the therapy initiation and planned with the treating physicians considering the specific indications for each drug.

Declaration of interest

C Pozzilli has received consulting fees, lecture fees and research funding from Almiral, Actelion, Bayer, Biogen, Genzyme, Merck & Co, Novartis, NuLife and Teva. L De Giglio has received travel grants from Biogen, Genzyme, Teva Pharmaceuticals and Novartis and consulting fees from Genzyme, Merck Serono, Novartis and Biogen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on his manuscript has been a consultant for Biogen, EMD Serono, Genentech, Genzyme, Novartis, and Teva; has received honoraria or speaker fees from Acorda, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, and Teva; and has received research grant support from Actelion, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, MedImmune, Novartis, Parexel, Patient-Centered Outcomes Research Institute, Sun Pharma, and TG Therapeutics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded