The last five years had as benchmark the development of new drugs for treatment of multiple sclerosis. Its treatment has become complex because other aspects must be considered on choosing therapeutic management, as previous use of immunosuppressors, time of disease and more recently virus load.
This issue brings an interesting research on the controversial risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis patients treated with Natalizumab. Nali et al.11 Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP. Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients. Arq Neuropsiq. 2014;72(12):960-965. present a brief review on the PML of patients submitted to Natalizumab treatment for relapsing-remitting multiple sclerosis and describe the results of virus load and JVC/DNA positivity in urine and blood, of a patient, after a 12 months’ follow-up.
The central question of this research11 Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP.
Natalizumab treatment for multiple sclerosis: updates and considerations for
safer treatment in JCV positive patients. Arq Neuropsiq.
2014;72(12):960-965.
seems to be the identification of patients with lower or higher risk for developing PML,
which must be considered on prescribing Natalizumab. PML is a devastating condition
leading to death or severe disability, that can be the result of reactivation of a
previous latent JCV viral infection of urinary tract22 Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B.
Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS)
trial. Eur J Neurol. 2014;21(2):299-304.
http://dx.doi.org/10.1111/ene.12304
https://doi.org/10.1111/ene.12304...
.
To date, there is no available method to determine which patient will have a highest risk
for developing PML and, also, which association can be established between JCV/DNA
positivity, JCV viremia and JCV viruria, and PML33 Sørensen PS. New management algorithms in multiple sclerosis.
Curr. Opin Neurol. 2014;27(3):246-59.
http://dx.doi.org/10.1097/WCO.0000000000000096
https://doi.org/10.1097/WCO.000000000000...
.
Actual statistics demonstrate that, among 118,000 patients using Natalizumab, 401 (0.34%)
developed PML44 Biogen Idec Medical Affairs. Tysabri (natalizumab) benefit/risk
update & PML risk stratification. 2013 [cited 2014 Nov] Available
from:
http://multiple-sclerosis-research.blogspot.com.br/2013/10/natalizumab-pml-update-september-2013.html
http://multiple-sclerosis-research.blogs...
. Although this is a low
percentage, one must evaluate this risk to decide, with the patient, to continue or to
change prescription, but it remains controversial. Despite the presence of rearranged
forms of JCV virus in urine, there was no viremia or concomitant increased viral load
after a 12 months treatment with Natalizumab11 Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP.
Natalizumab treatment for multiple sclerosis: updates and considerations for
safer treatment in JCV positive patients. Arq Neuropsiq.
2014;72(12):960-965.. These findings of Nali et al.11 Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP.
Natalizumab treatment for multiple sclerosis: updates and considerations for
safer treatment in JCV positive patients. Arq Neuropsiq.
2014;72(12):960-965. seem to reinforce the new management algorithm proposed by
Sørensen33 Sørensen PS. New management algorithms in multiple sclerosis.
Curr. Opin Neurol. 2014;27(3):246-59.
http://dx.doi.org/10.1097/WCO.0000000000000096
https://doi.org/10.1097/WCO.000000000000...
, where JCV
positivity may point out to another therapy. This conduct is discussed by Nali et
al.11 Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP.
Natalizumab treatment for multiple sclerosis: updates and considerations for
safer treatment in JCV positive patients. Arq Neuropsiq.
2014;72(12):960-965., on considering the risks of
drug holiday after 12 months of Natalizumab treatment.
A final consideration is that we still know very little on the causation of PML, and
other researches will be necessary to investigate also the influence of host
immunity55 Gorelik L, Lerner M, Bixler S, Grossman M, Schlain B, Simon K, et
al. Anti-JC virus antibodies: implications for PML risk stratification. Ann
Neurol. 2010;68(3):295-303. http://dx.doi.org/10.1002/ana.22128
https://doi.org/10.1002/ana.22128...
, that seems to be
relevant as we observe the discrepancy between the widespread prevalence of JCV and the
rare occurrence of PML66 Sørensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R,
Havrdova E, et al. Risk stratification for progressive multifocal
leukoencephalopathy in patients treated with natalizumab. Mult Scler.
2012;18(2):143-52. http://dx.doi.org/10.1177/1352458511435105
https://doi.org/10.1177/1352458511435105...
. This
discrepancy suggests the influence of factors other than an altered immune system, as
interactions between host and viral factors or viral alterations22 Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B.
Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS)
trial. Eur J Neurol. 2014;21(2):299-304.
http://dx.doi.org/10.1111/ene.12304
https://doi.org/10.1111/ene.12304...
. This will help us on deciding the best therapy for MS
patients, with less PML risk.
References
-
1Nali LHS, Moraes L, Fink MCD, Callegaro D, Romano CM, Oliveira ACP. Natalizumab treatment for multiple sclerosis: updates and considerations for safer treatment in JCV positive patients. Arq Neuropsiq. 2014;72(12):960-965.
-
2Bozic C, Subramanyam M, Richman S, Plavina T, Zhang A, Ticho B. Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS) trial. Eur J Neurol. 2014;21(2):299-304. http://dx.doi.org/10.1111/ene.12304
» https://doi.org/10.1111/ene.12304 -
3Sørensen PS. New management algorithms in multiple sclerosis. Curr. Opin Neurol. 2014;27(3):246-59. http://dx.doi.org/10.1097/WCO.0000000000000096
» https://doi.org/10.1097/WCO.0000000000000096 -
4Biogen Idec Medical Affairs. Tysabri (natalizumab) benefit/risk update & PML risk stratification. 2013 [cited 2014 Nov] Available from: http://multiple-sclerosis-research.blogspot.com.br/2013/10/natalizumab-pml-update-september-2013.html
» http://multiple-sclerosis-research.blogspot.com.br/2013/10/natalizumab-pml-update-september-2013.html -
5Gorelik L, Lerner M, Bixler S, Grossman M, Schlain B, Simon K, et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010;68(3):295-303. http://dx.doi.org/10.1002/ana.22128
» https://doi.org/10.1002/ana.22128 -
6Sørensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R, Havrdova E, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler. 2012;18(2):143-52. http://dx.doi.org/10.1177/1352458511435105
» https://doi.org/10.1177/1352458511435105
Publication Dates
-
Publication in this collection
Dec 2014
History
-
Received
23 Sept 2014 -
Accepted
01 Oct 2014