Background Natalizumab was the first monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) in the European Union in 2006. It is indicated for patients with high disease activity despite treatment with a β-interferon (IFN) or glatiramer acetate (GA) and in those with rapidly evolving severe RRMS. It is associated with the development of progressive multifocal leukoencephalopathy (PML).
Purpose To evaluate the effectiveness of natalizmab in ‘triple risk’ patients:
Long term natalizumab treatment (more than 2 years).
JCV (John Cunningham virus) antibody positive status, knowing that the risk of getting PML is greatest if you have all three risk factor listed above.
Material and methods Retrospective observational study including patients with at least one of the three risk factors for PML. Data were obtained from medical records from the neurology department in a university emergency hospital.
Results 30 patients, 21 women (70%).
Mean age 36.6 years, median time of natalizumab exposure: 37 months.
The PML factor risk distribution:
Time exposure more than 2 years: 25 patients (83.3%); 6 had >5 years of exposure).
Positive status JCV (test ELISA): 15 patients (50%).
Both risk factors: 10 patients (33,3%).
Immunosuppressive pretreatment: 2 patients (one with myasthenia gravis also).
Reason to use natalizumab:
4 patients firstline therapy, because of the aggressive form.
26 patients secondline therapy, because of treatment failure with IFN or GA.
One case was suspected of PML – suggestive MRI lesions, positive JCV, exposure >5 years, despite negative JVC-DNA, correlated with JCV antibody index value 3.37. PML was confirmed.
Conclusion Estimating or accurately predicting an individual’s risk of PML is still a major challenge. Our small sample size made an exhaustive evaluation difficult. One case of PML was detected. However, 97% of patients showed good adherence and better results than expected according to the triple risk factor distributions. Despite potential life threatening side effects such as PML, natalizumab remains one of the most effective therapies as an alternative in immunomodulator non-responders but for PML risk management for all patients, it is crucial to periodically evaluate if the expected benefit of natalizumab outweighs the risk.
No conflict of interest.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.