Cyclophosphamide Pulses Therapy after Natalizumab Discontinu | 46311

Journal of Multiple Sclerosis

ISSN - 2376-0389
NLM - 101654564


Cyclophosphamide Pulses Therapy after Natalizumab Discontinuation for Multiple Sclerosis: A Multicentre Study

Marco Capobianco, Marianna Lo Re, Francesca Sangalli, Lucia Moiola, Paola Perini, Paolo Gallo, Maura Danni, Leandro Provinciali, Annamaria Repice, Luca Massacesi, Silvia Messina, Francesco Patti, Alice Laroni8, Gian Luigi Mancardi, Eugenio Pucci, Massimiliano Calabrese, Antonio Bertolotto

Importance: Natalizumab discontinuation induces the recurrence of Multiple Sclerosis (MS) disease activity: Currently no therapeutic approach has been found able to abolish disease reactivation.

Objective: To collect data from patients with MS switching from natalizumab to cyclophosphamide.

Design: Retrospective multicentre study.

Setting: Nine Multiple Sclerosis Centers in Italy.

Participants: A total of 47 patients with clinically definite RR-MS switched to cyclophosphamide after natalizumab discontinuation. Two patients were excluded from the analysis because received less than 12 natalizumab infusions. The remaining 45 patients were subdivided into two main groups: Early Treatment (period of washout between natalizumab and cyclophosphamide 1 to 3 months), Late Treatment (washout between natalizumab and cyclophosphamide higher than 3 months).

Intervention: Cyclophosphamide intravenous pulses after natalizumab discontinuation.

Main outcome measure: Number of relapses, Expanded Disability Status Scale scores, number of new T2/fluid-attenuated inversion recovery lesions and contrast-enhancing lesions on brain magnetic resonance imaging, rebound effect, adverse events.

Results: In the Early Treatment group, only 3/23 patients (13%) experienced a clinical relapse and only 2 out of 13 (15%) patients showed brain Magnetic Resonance Imaging (MRI) activity at 3 months, while none developed MRI activity at 6 months after cyclophosphamide introduction. In the Late Treatment Group 12/22 patients (63%) had relapses during the washout period and 4/22 (40%) after the introduction of cyclophosphamide; MRI disease activity was shown in 5/9 (56%) at 3 months and in 5/14 (36%) at 6 months after cyclophosphamide introduction.

Conclusions and relevance: These data show that cyclophosphamide could be able to reduce disease reactivation after natalizumab, in particular with a short washout period after natalizumab discontinuation. It can be suggested that a short period (3-6 months) of cyclophosphamide monthly pulses could be used as “re-induction” treatment in patients discontinuing natalizumab.