From natalizumab to fingolimod in eight weeks — Immunological, clinical, and radiological data in quest of the optimal switch

Harrer, Andrea; Pilz, Georg; Oppermann, Katrin; Sageder, Marlene; Afazel, Shahrzad; Haschke-Becher, Elisabeth; Rispens, Theo; Vries, Annick de; McCoy, Mark R.; Stevanovic, Vlado; Hitzl, Wolfgang; Trinka, Eugen; Kraus, Jörg; Sellner, Johann; Wipfler, Peter

doi:10.1016/j.clim.2017.01.001

Cited by 7 publications

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“…However, we found no significant difference in concentration under natalizumab treatment when comparing patients with disease activity and patients without disease activity, which is in agreement with a recently published study of 12 patients switching from natalizumab to fingolimod. 26 In our study, the possible explanation could be that the clinical disease activity appeared after 3 months of natalizumab discontinuation when concentration of the drug had already decreased under therapeutic levels. 5 When comparing longitudinal natalizumab concentration in patients with and without disease activity, the mean concentration at 3 months was lower in patients who did not experience disease activity (0.8 vs 4.2 µg/mL).…”

Section: Discussionmentioning

confidence: 66%

Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

et al. 2017

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Background:Natalizumab is an effective treatment in relapsing-remitting multiple sclerosis (MS). Mainly because of the risk of progressive multifocal leukoencephalopathy (PML), a substantial proportion of John Cunningham (JC) virus–positive patients switch to fingolimod. Previous reports show a clear benefit when the duration of a washout (WO) period of natalizumab is 0–3 months in comparison to longer WO periods. However, there is no consensus regarding the optimal duration of a WO period under 3 months.Objective:We compared MS disease activity after different WO periods. In addition, we investigated several factors that possibly influence recurrence of disease activity, including serum natalizumab concentration and lymphocyte counts.Methods:From a prospective observational cohort study of natalizumab-treated patients, we selected 52 patients who switched to fingolimod. We divided the patients in three groups (<6 weeks, 6–8 weeks, >8 weeks WO). Serum natalizumab concentration and lymphocyte count were assessed during and after natalizumab treatment.Results:Patients with a WO period of >8 weeks had a significant higher recurrence of disease activity (odds ratio, 6.8; 95% confidence interval, 1.4–32.8) compared to patients with a WO period of <6 weeks. Serum natalizumab concentration and lymphocyte count did not predict recurrence of disease activity.Interpretation:A short WO period decreases the risk of recurrence of disease activity. The possible impact of a short WO period on the risk of carry-over PML in JC virus–positive patients remains uncertain.

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Section: Discussionmentioning

confidence: 66%

Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

et al. 2017

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“…According to other authors [71,72,73], we think it is important to analyse in larger cohorts of patients the immunological consequences of natalizumab discontinuation, in order to find out a useful biomarker for an effective therapeutic switch. …”

Section: Discussionmentioning

confidence: 99%

“…The results showed that Th17 and IL-17 levels increased during prolonged natalizumab treatment, returned to baseline levels after withdrawal and resulted almost undetectable in patients who experienced relapses during the natalizumab washout period [72]. Looking for a biomarker for a safe and effective change from natalizumab to fingolimod, Harrer and colleagues [73] monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two therapies; they studied 12 MS patients previously treated with natalizumab (for at least 12 months) during the eight-week wash out period and the six months of fingolimod treatment. The authors found an high interindividual variability and the only linkage with MS reactivation was an higher frequencies of memory CD8 lymphocytes after six months on fingolimod, thus, none of the analyzed parameters showed a potential role as a prognostic biomarker for the outcome of the switch [73].…”

Section: Literature Review Sectionmentioning

confidence: 99%

Natalizumab in Multiple Sclerosis: Long-Term Management

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et al. 2017

IJMS

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Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients’ clinical features and preferences.

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“…Thereby, we could show statistical significant differences in natalizumab cell-bound levels between different treatment intervals (natalizumab saturation after 4 weeks is 64%, after 5 weeks is 55.2%, and after 8 weeks is 34%), while higher interindividual differences occur with longer treatment intervals. Harrer et al 9 could demonstrate higher natalizumab saturation levels after a 8-week treatment holiday in 12 patients (CD8 cells, 57%; interquartile range, 26%–64% and CD4 cells, 67%; interquartile range, 38%–69%) with high interindividual variability.…”

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confidence: 97%

Letter to the editor on the paper: “The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing”

et al. 2017

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From natalizumab to fingolimod in eight weeks — Immunological, clinical, and radiological data in quest of the optimal switch

Cited by 7 publications

References 30 publications

Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

Switching natalizumab to fingolimod within 6 weeks reduces recurrence of disease activity in MS patients

Natalizumab in Multiple Sclerosis: Long-Term Management

Letter to the editor on the paper: “The majority of natalizumab-treated MS patients have high natalizumab concentrations at time of re-dosing”

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