Progressive multifocal leukoencephalopathy after fingolimod treatment

Joseph R. Berger, Bruce A. Cree, Benjamin Greenberg, Bernhard Hemmer, Brian J. Ward, Victor M. Dong, Martin Merschhemke

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Objective We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.MethodsThe Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.ResultsAs of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/L).ConclusionsThe risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.

Original languageEnglish (US)
Pages (from-to)E1815-E1821
JournalNeurology
Volume90
Issue number20
DOIs
StatePublished - Jan 1 2018

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Progressive Multifocal Leukoencephalopathy
Therapeutics
Fingolimod Hydrochloride
Confidence Intervals
Safety
Lymphopenia
Incidence
Lymphocyte Count
Natalizumab

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Berger, J. R., Cree, B. A., Greenberg, B., Hemmer, B., Ward, B. J., Dong, V. M., & Merschhemke, M. (2018). Progressive multifocal leukoencephalopathy after fingolimod treatment. Neurology, 90(20), E1815-E1821. https://doi.org/10.1212/WNL.0000000000005529

Progressive multifocal leukoencephalopathy after fingolimod treatment. / Berger, Joseph R.; Cree, Bruce A.; Greenberg, Benjamin; Hemmer, Bernhard; Ward, Brian J.; Dong, Victor M.; Merschhemke, Martin.

In: Neurology, Vol. 90, No. 20, 01.01.2018, p. E1815-E1821.

Research output: Contribution to journalArticle

Berger, JR, Cree, BA, Greenberg, B, Hemmer, B, Ward, BJ, Dong, VM & Merschhemke, M 2018, 'Progressive multifocal leukoencephalopathy after fingolimod treatment', Neurology, vol. 90, no. 20, pp. E1815-E1821. https://doi.org/10.1212/WNL.0000000000005529
Berger, Joseph R. ; Cree, Bruce A. ; Greenberg, Benjamin ; Hemmer, Bernhard ; Ward, Brian J. ; Dong, Victor M. ; Merschhemke, Martin. / Progressive multifocal leukoencephalopathy after fingolimod treatment. In: Neurology. 2018 ; Vol. 90, No. 20. pp. E1815-E1821.
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abstract = "Objective We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.MethodsThe Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.ResultsAs of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73{\%}) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/L).ConclusionsThe risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95{\%} confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95{\%} confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.",
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N2 - Objective We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.MethodsThe Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.ResultsAs of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/L).ConclusionsThe risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.

AB - Objective We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.MethodsThe Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.ResultsAs of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/L).ConclusionsThe risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.

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