Natalizumab is an effective strategy for achieving disease control in those with highly-active MS, but owing to the risk of progressive multifocal leucoencephalopathy (PML), often needs to be de-escalated. However, discontinuation of natalizumab therapy is not without its own risks; the biggest risk being rebound activity, which rarely may be a flare beyond that of pre-treatment disease activity.
The RESTORE study showed much to the surprise of all that rebound may begin as early as 4-8 weeks after natalizumab discontinuation, this despite switching to either glatiramer acetate (Copaxone), interferon beta therapy or pulsed methylprednisolone.
Early switch (less than 3 months after stopping natalizumab) to fingolimod , however, seems to be superior to both interferon beta and glatiramer acetate in reducing the risk of rebound. Whilst, in a smaller study rituximab was found to be superior to fingolimod and dimethylfumerate, in terms reducing radiological activity based on number of enhancing lesions on MRI.
Little is know about how the other highly active therapies fare on preventing rebound. Alemtuzumab notably seems to be like rituximab, better than fingolimod; in one study after one year of treatment the fingolimod group had fewer without a relapse (54% fingolimod vs. 77% alemtuzumab) and MRI activity (50% fingolimod vs. 74% alemtuzumab) than alemtuzumab. And recently this week, in a case report Federle et al., following a particularly severe rebound after natalizumab discontinuation (12 new brain and spinal cord lesions, and an increase in disability scores from EDSS 1.5 to 6.5; see figure below), alemtuzumab stopped the development of new lesions and led to an improvement in the EDSS score to 4.
The authors suggest that alemtuzumab should be considered as an immediate rescue strategy for cases where rebound is catastrophic. Moreover, the JCV index, in this particular case was high at 3.63. Recommencing natalizumab or using maintenance strategies that lead to chronic lymphodepletion, are therefore not valid long-term strategies. When commencing natalizumab, sequencing of treatments post-natalizumab based on risk-minimization is important to consider at the very start.
Mult Scler Relat Disord. 2019 Mar 5;30:262-264. doi: 10.1016/j.msard.2019.03.002. [Epub ahead of print]
Alemtuzumab as rescue therapy in case of multiple sclerosis rebound following Natalizumab break: Clinical case and literature review.
Federle L1, Puthenparampil M2, Stenta G1, Paolo G1, Francesco P1.
Introduction: Natalizumab break exposes multiple sclerosis (MS) patients to a high risk of disease reactivation or rebound, whose prevention and treatment constitute a clinical challenge.
Case Presentation: We describe a dramatic case of MS rebound, characterized by the development of severe neurological and psychiatric symptoms, following natalizumab break. Alemtuzumab rapidly and completely suppressed brain inflammation as demonstrated by clinical and radiological findings.
Conclusions: Our case further adds to the available literature evidence on Alemtuzumab as first-choice rescue therapy following Natalizumab discontinuation.