Abstract
BackgroundProgressive multifocal leukoencephalopathy (PML) is one of the major risks of natalizumab therapy. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing.ObjectivesWe addressed the following questions: How do natalizumab-treated multiple sclerosis patients and their treating physicians assess and deal with PML risk? Is PML risk the real reason for natalizumab discontinuation?Methods699 natalizumab-treated multiple sclerosis patients and 99 physicians were included in this prospective observational study. Questionnaires were completed at 5 different time points. Patients were stratified into 5 subgroups according to the presence of PML risk factors (prior immunosuppression, anti-JCV antibody status, treatment duration). Patients with prior immunosuppression (n = 30, treated by n = 7 physicians) were excluded from analyses, because patient numbers were too small. Patients’ anti-JCV antibody index was not considered because data recruitment ended in 2014. Using Bayesian network and regression analysis, we examined the relationship between different patient- and physician-related factors and patients’ discontinuation of natalizumab.ResultsPatients of all subgroups and physicians assessed the PML risk as low. Overall patient adherence to natalizumab was high (87%). Only 13% of patients discontinued therapy. Natalizumab treatment cessation was associated with different patient- and physician-related factors (physicians’ assessment of general PML risk, number of treated patients per year, natalizumab treatment duration, relapses during the course of study) upon which only physicians’ judgment on treatment continuation, patients’ perception of personal PML risk, and JCV seroconversion showed significant relationships.ConclusionAccording to the currently employed risk stratification algorithm, the objective PML risk probably doesn’t play a dominant role in a patients’ decision to continue or stop natalizumab treatment. The decision-making process is rather guided by subjective views and experiences of patients and treating neurologists. Treating physicians should consider this discrepancy in their advice to improve the risk-benefit-ratio for the individual patient.
Highlights
Natalizumab (NTZ) (Tysabri; Biogen, Cambrige, MA, USA), a humanized recombinant monoclonal antibody that inhibits leukocyte extravasation into the central nervous system by targeting VLA-4, was approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS) in the US in 2004 on the basis of interim analyses of two large phase III trials (AFFIRM and SENTINEL) [1,2]
Natalizumab treatment cessation was associated with different patient- and physicianrelated factors upon which only physicians’ judgment on treatment continuation, patients’ perception of personal Progressive multifocal leukoencephalopathy (PML) risk, and John Cunningham virus (JCV) seroconversion showed significant relationships
The decision-making process is rather guided by subjective views and experiences of patients and treating neurologists
Summary
Natalizumab (NTZ) (Tysabri; Biogen, Cambrige, MA, USA), a humanized recombinant monoclonal antibody that inhibits leukocyte extravasation into the central nervous system by targeting VLA-4, was approved for the treatment of active relapsing-remitting multiple sclerosis (RRMS) in the US in 2004 on the basis of interim analyses of two large phase III trials (AFFIRM and SENTINEL) [1,2]. Three independent factors identified in all NTZ-treated patients with PML are established biomarkers for PML risk and are currently employed for PML risk stratification: the duration of NTZ treatment, especially after 24 months, prior use of immunosuppressants (IMS +), and positive serostatus for anti-JCV antibodies (JCV Ab +) [8]. This three-stage risk stratification algorithm does not allow for a precise prediction of PML risk in individual patients [4,9]. Despite introduction of the currently employed PML risk stratification algorithm, the incidence of natalizumab-associated PML cases is not decreasing
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
