Is the risk of progressive multifocal leukoencephalopathy the real reason for natalizumab discontinuation in patients with multiple sclerosis?

TY - JOUR

T1 - Is the risk of progressive multifocal leukoencephalopathy the real reason for natalizumab discontinuation in patients with multiple sclerosis?

AU - Krämer, Julia

AU - Tenberge, Jan-Gerd

AU - Kleiter, Ingo

AU - Gaissmaier, Wolfgang

AU - Ruck, Tobias

AU - Heesen, Christoph

AU - Meuth, Sven G

PY - 2017/4/13

Y1 - 2017/4/13

N2 - BACKGROUND: Progressive 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.OBJECTIVES: We 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?METHODS: 699 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.RESULTS: Patients 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.CONCLUSION: According 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.

AB - BACKGROUND: Progressive 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.OBJECTIVES: We 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?METHODS: 699 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.RESULTS: Patients 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.CONCLUSION: According 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.

KW - Adult

KW - Aged

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Leukoencephalopathy, Progressive Multifocal

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Natalizumab

KW - Risk Factors

KW - Journal Article

KW - Multicenter Study

KW - Observational Study

U2 - 10.1371/journal.pone.0174858

DO - 10.1371/journal.pone.0174858

M3 - SCORING: Journal article

C2 - 28406921

VL - 12

SP - e0174858

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

ER -