The following recommendations paper from a group of EU experts doesn’t address the real issues with using alemtuzumab. Why? May because it was drafted and co-written by a third-party vendor and subsequently proof-read and checked by Sanofi-Genzyme.
Baker PhD, and Neli Boyanova MD, of Sanofi Genzyme. Editorial
support (assistance in drafting and editing of the manuscript text and
tables, as directed by authors, data checking and incorporation of
comments from reviewers, and assisting with the submission process) was provided by Steve Banner at Fishawack Communications Ltd.,
funded by Sanofi Genzyme. This was the only funding provided for
the development of this manuscript. This article is based on the
outcomes of a European Advisory Board, held in Vienna, Austria, in
November 2013, during which a panel of European MS experts
provided insights, guidance, and recommendations regarding best
practices for alemtuzumab treatment and compliance with ongoing
monitoring requirements designed to mitigate potential adverse
Compliance with Ethical Standards
Funding The advisory board was funded by Sanofi Genzyme. All
advisors received honoraria payments for their participation. Open
access fee was funded by the Medical University of Innsbruck.’
- Should you consider alemtuzumab in patients with MS who have only had one clinical attack?
- How exactly do you transition patients at high-risk of PML from natalizumab to alemtuzumab?
- How exactly do you transition patients from fingolimod to alemtuzumab? Would you be guided by the peripheral blood lymphocyte counts? Would these principles apply to other DMTs associated with lymphopaenia?
- How do you define an alemtuzumab treatment failure?
- How many courses of alemtuzumab do you give before you consider the pwMS are non-responders?
- What treatments can be given post-alemtuzumab? How would you give these treatments?
- What do you do if someone has a relapse several months before the next course of alemtuzumab is due? Can you give the next course early?
- Can you give the next course of alemtuzumab if someone has persistent lymphopaenia post-alemtuzumab; if no, at what level would you recommend not retreating (grade 1 >800-1000/mm3, grade 2 > 500-800/mm3, grade 3 > 200-500/mm3 or grade 4 < 200/mm3)?
- When do you test for neutralising anti-alemtuzumab antibodies (NABs)? How do you test for NABs?
- What do you do if someone does not deplete their peripheral lymphocytes with alemtuzumab? Do you call these individuals non-responders?
- Apart from autoimmune thyroid, anti-GBM and ITP, what about the other autoimmune diseases that you need to be vigilant about post alemtuzumab; i.e. neutropaenia, haemolytic aneamia, bullous skin disease, acquired haemophilia, pernicious anaemia, vasculitis, TTP, etc.?
- What about infectious complications post alemtuzumab, i.e. listeriosis, nocardiosis, zoster?
- What recommendations regarding Listeria prophylaxis would you give? What works, what doesn’t?
- What should we be telling pwMS to do regarding preventing Listerial, Nocardial and fungal infections?
- Should we be using anti-viral prophylaxis with alemtuzumab?
- What about baseline TB, HIV, hepatitis, and HPV (cervical smear) screening?
- When would live vaccines be potentially safe post-alemtuzumab?
- What about travel and exposure to exotic infections?
- What is the optimal protocol for reducing infusion related events? Can you avoid steroids?
- Is there any way of predicting who will develop secondary autoimmunity? Are there any therapeutic strategies to prevent secondary autoimmunity?
- What about CMV reactivation post-alemtuzumab? Is it a problem? Should we screen for it?
- What is the best strategies for engaging pwMS with their own pharmacovigilance? What do you do if someone is non-compliant with their pharmacovigilance? Can you use point-of-care testing for alemtuzumab pharmacovigilance?
- What do you do if someone develops PML post-alemtuzumab? Are there any strategies for managing this situation?
Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile. The European Union indication provides physicians with significant flexibility regarding treatment decisions, affording the opportunity for individualized treatment. Thus, alemtuzumab may be an appropriate treatment choice across a broad range of patients with RRMS, including, for example, treatment-naïve patients with active disease, patients with highly active disease, or for patients relapsing on prior DMTs. There are several practicalities to consider when using alemtuzumab, including the unique dosing regimen, administered via intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later, and as-needed retreatment (3 consecutive days at least 12 months after the last course) in cases of disease recurrence. Additionally, routine monthly monitoring is required for up to 48 months after the last infusion to promptly identify potentially serious autoimmune adverse events. Given these considerations, it is beneficial to gain insight into how alemtuzumab is being used in the real-world clinical setting. Here, we report recommendations from European multiple sclerosis experts regarding best practices for alemtuzumab treatment, including management of adverse events and compliance with ongoing safety monitoring requirements.