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Offline agate

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(Abst.) Switching from Tysabri to Gilenya...
« on: May 31, 2015, 03:53:55 pm »
From PubMed, May 31, 2015:

Quote
Neurology. 2015 May 29.

Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS

Kappos L1, Radue EW2, Comi G2, Montalban X2, Butzkueven H2, Wiendl H2, Giovannoni G2, Hartung HP2, Derfuss T2, Naegelin Y2, Sprenger T2, Mueller-Lenke N2, Griffiths S2, von Rosenstiel P2, Gottschalk R2, Zhang Y2, Dahlke F2, Tomic D2; TOFINGO study group.

Author information

1From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ. lkappos@uhbs.ch.

2From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.

OBJECTIVE:

To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in patients switching from natalizumab to fingolimod.

METHODS:

In this multicenter, double-blind, placebo-controlled trial (TOFINGO), patients with relapsing-remitting multiple sclerosis (RRMS) were randomized 1:1:1 to 8-, 12-, or 16-week WO followed by fingolimod treatment over 32 weeks from last natalizumab infusion (LNI). Brain MRI was performed at baseline and weeks 8, 12, 16, 20, and 24.

RESULTS:

Of 142 enrolled and randomized patients, 112 (78.9%) completed the study (8 weeks, n = 41/50; 12 weeks, n = 31/42; 16 weeks, n = 40/50). Number (95% confidence interval [CI]) of active (new/newly enlarged T2) lesions from LNI through 8 weeks of fingolimod treatment (primary outcome) was similar in the 8-week (2.1 [1.7-2.6]) and 12-week WO groups (1.7 [1.3-2.2]) and higher in the 16-week WO group (8.2 [7.3-9.1]). During the WO period only, the number (95% CI) of active lesions increased with increasing WO duration (8 weeks, 0.4 [0.2-0.6]; 12 weeks, 2.1 [1.6-2.6]; 16 weeks, 3.6 [3.0-4.2]). Over the 24 weeks from LNI, gadolinium-enhancing T1 lesion counts were lower in the 8-week WO group (14.1 [5.67-22.53]) than in the 12-week (21.3 [1.41-41.19]) or 16-week (18.5 [8.40-28.60]) WO groups. More patients were relapse-free in the 8-week (88%) and 12-week (91%) WO groups than the 16-week WO group (84%). Sixty-eight percent of patients experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or opportunistic infections occurred.

CONCLUSIONS:

Initiating fingolimod therapy 8-12 weeks after natalizumab discontinuation is associated with a lower risk of MRI and clinical disease reactivation than initiation after 16-week WO.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that for patients with RRMS switching from natalizumab to fingolimod, shorter natalizumab WO periods are associated with less MRI disease activity than are longer WO periods.

The abstract can be seen here.
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Re: (Abst.) Switching from Tysabri to Gilenya...
« Reply #1 on: June 27, 2015, 11:43:41 am »
More on this--in Multiple Sclerosis News Today, June 17, 2015:

Quote
Researchers Suggest Short Transition Period Between Natalizumab and Fingolimod Therapies to Control RRMS Disease Activity

 Patricia Silva, PhD PATRICIA SILVA, PHD


An international team led by researchers at the University Hospital Basel in Switzerland revealed that a short period of 8 to 12 weeks is the optimal timing to be considered when patients with relapsing-remitting multiple sclerosis (RRMS) are switched from natalizumab to fingolimod therapy. The study was recently published in the journal Neurology and is entitled “Switching from natalizumab to fingolimod, A randomized, placebo-controlled study in RRMS.”

...

The most frequent form of multiple sclerosis is RRMS, which is clinically characterized by recurring episodes of neurological symptoms. Natalizumab is a humanized monoclonal antibody used in the treatment of RRMS patients. However, its use is associated with some clinical complications such as persistent anti-natalizumab antibodies (natalizumab has a long elimination half-life and prolonged immunosuppressive effects), suboptimal efficacy, tolerability issues, and the development of progressive multifocal leuko-encephalopathy (PML, a severe opportunistic brain infection by the JC virus). As natalizumab has an intravenous formulation, patients often prefer an oral therapy. Due to these factors, a switch from natalizumab to other therapies is therefore often considered. Natalizumab discontinuation can, in turn, lead to a rapid return of relapse activity and magnetic resonance imaging (MRI) lesions to levels similar to the ones prior to the treatment.

Oral fingolimod (0.5 mg, once-daily) is an efficient therapy for relapsing forms of MS. Previous studies have suggested that fingolimod has a beneficial effect in terms of relapses in patients who discontinued natalizumab treatment, and could therefore be considered a potential suitable switch therapy from natalizumab.

In this study, researchers conducted a randomized, multicenter, double-blind, placebo-controlled trial (TOFINGO) to determine the optimal timing for initiating fingolimod therapy after natalizumab discontinuation in 142 RRMS patients. The goal is to maintain disease control and avoid potentially harmful additive effects on immune surveillance. The team tested the intervals of 8, 12 and 16 weeks between the last natalizumab infusion and fingolimod treatment over 32 weeks. Brain MRI recurrence and clinical disease activity were evaluated.

Researchers found that in total, 78.9% (112) of the patients completed the study. The number of active MRI lesions was found to increase according with the duration of the interval between the two therapies. More patients were found to be relapse-free in the 8-week (88%) and 12-week (91%) periods in comparison to the 16-week period (84%). Of the cohort, 68% of the patients experienced mild or moderate adverse events with no major differences between the groups analyzed. No unusually severe relapses or opportunistic infections were reported.

The team concluded that patients with RRMS switching from natalizumab to fingolimod therapy should undergo a short period of 8 to 12 weeks between therapies, as this time interval is associated with less MRI disease activity than longer periods. The authors suggest that additional studies should be performed to determine whether an interval shorter than 8 weeks would further improve disease control with reasonable risks.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.