Abstract
Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients’ clinical features and preferences.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) [1]; it is a frequent illness, affecting more than 2.3 million people in the world [2]
Several studies [5,6,7,8] demonstrated that one of the mechanisms involved in the adhesion and migration of lymphocytes to the CNS is related to the interaction of the α4β1 integrin expressed on their surface with the vascular-cell adhesion molecule 1 (VCAM-1) on the surface of vascular endothelial cells of CNS blood vessels
Natalizumab was initially approved by the US Food and Drug Adminsitration (FDA) in 2004 for relapsing remitting multiple sclerosis (RRMS), upon the interim results of two phase-III trials, the AFFIRM and SENTINEL [12,13], but in 2005 it was taken off the market after the occurrence of three cases of progressive multifocal leukoencephalopathy (PML): two in MS patients and one in a Crohn’s disease (CD) patient [14,15,16]
Summary
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) [1]; it is a frequent illness, affecting more than 2.3 million people in the world [2]. No PML cases have been reported in MS patients before the introduction of natalizumab [23]; in case of JCV reactivation, the infection affects the myelin-producing oligodendrocytes, resulting in severe demyelination [24,25,26,27]. The anti-JC virus antibody level in serum or plasma has been identified as a further risk of natalizumab-associated PML [37] According to these data, European Medicines Agency (EMA) has recently updated the estimate risk for PML in seropositive JCV antibody patients treated with natalizumab [38]; the risk is small at antibody index values of 0.9 or less (0.1–0.6/1000), and increases substantially in patients with index values above 1.5 who have been treated with natalizuab for more than 24 administrations (0.9–10/1000) [38]. Besides the risk of PML, other circumstances should lead to the decision to stop natalizumab therapy, such as the detection of anti-natalizumab antibodies, incomplete efficacy, tolerability matters, or patient preference for oral therapies [44]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
