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Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring.

Alroughani RA, Aref HM, Bohlega SA, Dahdaleh MP, Feki I, Al Jumah MA, Al-Kawi MZ, Koussa SF, Sahraian MA, Alsharoqi IA, Yamout BI - BMC Neurol (2014)

Bottom Line: Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab.In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML.Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

View Article: PubMed Central - HTML - PubMed

Affiliation: Amiri Hospital, Arabian Gulf Street, 73767 Kuwait City, Kuwait. alroughani@gmail.com.

ABSTRACT

Background: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies.

Methods: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region.

Results: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients.

Conclusions: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

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Related in: MedlinePlus

Regional recommendations for using natalizumab in anti-JCV antibody-positive patients. B/R: Benefit/risk; IS: immunosuppression; JCV: John Cunningham virus.
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Figure 5: Regional recommendations for using natalizumab in anti-JCV antibody-positive patients. B/R: Benefit/risk; IS: immunosuppression; JCV: John Cunningham virus.

Mentions: Figures 3, 4 and 5 show the algorithm developed during the discussion. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease on the basis of its established efficacy in Phase III studies. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. Several factors including prior immunosuppressant therapy, anti-JCV antibody status and patient choice may contribute to the selection of natalizumab. A complete blood count and a cranial MRI scan (within 3 months of starting natalizumab therapy) are recommended at baseline. This enables comparison with subsequent scans that may be done to investigate the cause of new or worsening neurological symptoms once on natalizumab therapy. Figure 3 shows recommendations for maximising the safety of natalizumab. Treatment should be stopped if hypersensitivity reactions or persistent anti-drug antibodies occur. If infusion reactions occur, treatment can be continued with monitoring and pre-medication. Treatment is discontinued in the event of non-response, pregnancy, suspicion of PML, definite adverse events or a change in the benefit–risk evaluation. A low threshold to withhold natalizumab and investigate with MRI and CSF testing is recommended when a diagnosis of possible PML is entertained. If a thorough neurological assessment cannot rule out PML, natalizumab must be suspended and not restarted until a disorder other than MS has been excluded with confidence. Natalizumab can be resumed only if the diagnosis of PML is discounted [43].


Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring.

Alroughani RA, Aref HM, Bohlega SA, Dahdaleh MP, Feki I, Al Jumah MA, Al-Kawi MZ, Koussa SF, Sahraian MA, Alsharoqi IA, Yamout BI - BMC Neurol (2014)

Regional recommendations for using natalizumab in anti-JCV antibody-positive patients. B/R: Benefit/risk; IS: immunosuppression; JCV: John Cunningham virus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3927624&req=5

Figure 5: Regional recommendations for using natalizumab in anti-JCV antibody-positive patients. B/R: Benefit/risk; IS: immunosuppression; JCV: John Cunningham virus.
Mentions: Figures 3, 4 and 5 show the algorithm developed during the discussion. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease on the basis of its established efficacy in Phase III studies. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. Several factors including prior immunosuppressant therapy, anti-JCV antibody status and patient choice may contribute to the selection of natalizumab. A complete blood count and a cranial MRI scan (within 3 months of starting natalizumab therapy) are recommended at baseline. This enables comparison with subsequent scans that may be done to investigate the cause of new or worsening neurological symptoms once on natalizumab therapy. Figure 3 shows recommendations for maximising the safety of natalizumab. Treatment should be stopped if hypersensitivity reactions or persistent anti-drug antibodies occur. If infusion reactions occur, treatment can be continued with monitoring and pre-medication. Treatment is discontinued in the event of non-response, pregnancy, suspicion of PML, definite adverse events or a change in the benefit–risk evaluation. A low threshold to withhold natalizumab and investigate with MRI and CSF testing is recommended when a diagnosis of possible PML is entertained. If a thorough neurological assessment cannot rule out PML, natalizumab must be suspended and not restarted until a disorder other than MS has been excluded with confidence. Natalizumab can be resumed only if the diagnosis of PML is discounted [43].

Bottom Line: Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab.In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML.Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

View Article: PubMed Central - HTML - PubMed

Affiliation: Amiri Hospital, Arabian Gulf Street, 73767 Kuwait City, Kuwait. alroughani@gmail.com.

ABSTRACT

Background: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies.

Methods: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region.

Results: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients.

Conclusions: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

Show MeSH
Related in: MedlinePlus