Can dimethyl-fumarate be a good treatment choice after natalizumab discontinuation?
Author(s): ,
G Farina
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy
,
M Pitteri
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy
,
R Magliozzi
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy;Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom
,
M Castellaro
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy;Department of Information Engineering
,
V Camera
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy
,
C Romualdi
Affiliations:
Department of Biology, University of Padova, Padova, Italy
,
A Bertoldo
Affiliations:
Department of Information Engineering
,
S Monaco
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy
M Calabrese
Affiliations:
Neurology B, Dept. of Neurological and Movement Sciences, University of Verona, Verona, Italy
ECTRIMS Online Library. Farina G. 09/16/16; 145838; P1154
Gabriele Farina
Gabriele Farina
Contributions
Abstract

Abstract: P1154

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: Several studies demonstrated the impressive efficacy and the good tolerability profile of Natalizumab (NTZ) in Multiple Sclerosis (MS) patients. Although the long-term safety of NTZ therapy is burdened by the risk of progressive multifocal leukoencephalopathy (especially in anti-JCV seropositive patients treated for more than two years) the NTZ discontinuation enlightened the risk of disease reactivation. Previous data indicated that Fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from NTZ.

Aim: In this study we wanted to explore the efficacy of Dimethyl-fumarate (DMF) in controlling MS reactivation after NTZ discontinuation.

Patients and methods: 37 relapsing-remitting MS patients having high titre of JCV-Ab and more than 2 years of treatment, were shifted from NTZ to DMF after a mean of 1 month washout period. An increasing dose scheme as the following was used: 120 mg BID for 1 week, then 240 mg BID.

Expanded Disability Status Scale (EDSS) was evaluated monthly for a mean follow-up period of 9.8

(±3; range 5.5-16) months. Brain 3T MRI was obtained at the beginning of DMF and every 3 months after therapy initiation. Three patients had less than 6 months of follow up to date and therefore were excluded from the analysis.

The number of relapses, the disability (EDSS) progression and the MRI activity (new Gad+ lesions, new T2 lesions, new enlarging T2 lesions and new cortical lesions) were evaluated.

The NEDA-3 patients defined by no clinical relapses, no disability progression and no MRI activity were also calculated.

Results: Among the 34 analysed patients and after 9 months of follow up, 31 (91%) can be considered NEDA-3. One patient (2.9%) had a clinical relapse plus MRI activity while 2 patients (5.9%) showed MRI activity only. In all cases, disease activity occurred within the first 3 months of the DMF treatment. The side effects were similar to the phase 3 main clinical trials and no dropouts were registered.

Discussion and conclusion: Although DMF does not seem to completely eliminate the possibility of disease reactivation, our results indicate that it might be a promising drug for those patients who shall discontinue NTZ. Additional data on larger sample sizes should confirm this hypothesis.

Disclosure:

Gabriele Farina: nothing to disclose.

Marco Pitteri: nothing to disclose.

Roberta Magliozzi: nothing to disclose.

Marco Castellaro: nothing to disclose.

Valentina Camera: nothing to disclose.

Chiara Romualdi: nothing to disclose.

Alessandra Bertoldo: nothing to disclose.

Salvatore Monaco: nothing to disclose.

Massimiliano Calabrese: advisory board membership: Bayer-Shering, Genzyme, Biogen Idec; payment for development of educational presentations including service on speakers bureaus: Biogen-Elan, Genzyme, TEVA, Bayer-Schering; travel/accommodation expenses covered or reimbursed: Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA.

Abstract: P1154

Type: Poster

Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression

Background: Several studies demonstrated the impressive efficacy and the good tolerability profile of Natalizumab (NTZ) in Multiple Sclerosis (MS) patients. Although the long-term safety of NTZ therapy is burdened by the risk of progressive multifocal leukoencephalopathy (especially in anti-JCV seropositive patients treated for more than two years) the NTZ discontinuation enlightened the risk of disease reactivation. Previous data indicated that Fingolimod does not exert clinical activity quickly enough to stop MS reactivation after a break from NTZ.

Aim: In this study we wanted to explore the efficacy of Dimethyl-fumarate (DMF) in controlling MS reactivation after NTZ discontinuation.

Patients and methods: 37 relapsing-remitting MS patients having high titre of JCV-Ab and more than 2 years of treatment, were shifted from NTZ to DMF after a mean of 1 month washout period. An increasing dose scheme as the following was used: 120 mg BID for 1 week, then 240 mg BID.

Expanded Disability Status Scale (EDSS) was evaluated monthly for a mean follow-up period of 9.8

(±3; range 5.5-16) months. Brain 3T MRI was obtained at the beginning of DMF and every 3 months after therapy initiation. Three patients had less than 6 months of follow up to date and therefore were excluded from the analysis.

The number of relapses, the disability (EDSS) progression and the MRI activity (new Gad+ lesions, new T2 lesions, new enlarging T2 lesions and new cortical lesions) were evaluated.

The NEDA-3 patients defined by no clinical relapses, no disability progression and no MRI activity were also calculated.

Results: Among the 34 analysed patients and after 9 months of follow up, 31 (91%) can be considered NEDA-3. One patient (2.9%) had a clinical relapse plus MRI activity while 2 patients (5.9%) showed MRI activity only. In all cases, disease activity occurred within the first 3 months of the DMF treatment. The side effects were similar to the phase 3 main clinical trials and no dropouts were registered.

Discussion and conclusion: Although DMF does not seem to completely eliminate the possibility of disease reactivation, our results indicate that it might be a promising drug for those patients who shall discontinue NTZ. Additional data on larger sample sizes should confirm this hypothesis.

Disclosure:

Gabriele Farina: nothing to disclose.

Marco Pitteri: nothing to disclose.

Roberta Magliozzi: nothing to disclose.

Marco Castellaro: nothing to disclose.

Valentina Camera: nothing to disclose.

Chiara Romualdi: nothing to disclose.

Alessandra Bertoldo: nothing to disclose.

Salvatore Monaco: nothing to disclose.

Massimiliano Calabrese: advisory board membership: Bayer-Shering, Genzyme, Biogen Idec; payment for development of educational presentations including service on speakers bureaus: Biogen-Elan, Genzyme, TEVA, Bayer-Schering; travel/accommodation expenses covered or reimbursed: Novartis Pharma, Genzyme, Biogen idec, Merck Serono, Bayer-Schering, TEVA.

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