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Neurology and Therapy
Published in: Neurology and Therapy 1/2017

Open Access 01-06-2017 | Original Research

Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial

Authors: Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Nobuhisa Ohtsuka, Yan Ling, Shinichi Torii, Nisha Lucas, Geoffrey Kuesters, Deb Steiner, J. T. Tibung, on behalf of the Natalizumab Trial Principal Investigators

Published in: Neurology and Therapy | Issue 1/2017

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Abstract

Introduction

The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients.

Methods

A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks. Multiple sclerosis relapses, changes in Expanded Disability Status Scale (EDSS) scores, and adverse events were assessed at regular intervals. Anti-natalizumab and anti-JC virus (JCV) antibodies were measured.

Results

After 2 years of natalizumab treatment, the mean adjusted annualized relapse rate was 0.30 (95% confidence interval [CI]: 0.18–0.52) among previously-on-placebo patients and 0.13 (95% CI: 0.05–0.29) among previously-on-natalizumab patients. The mean change in EDSS score from baseline to week 120 was −0.03 among previously-on-placebo patients and −0.18 among previously-on-natalizumab patients. In both groups, >90% of patients experienced ≥1 adverse event. Two previously-on-placebo patients developed persistently positive anti-natalizumab antibodies. Approximately 65% of all patients tested positive for anti-JCV antibodies at open-label treatment initiation. No deaths or progressive multifocal leukoencephalopathy cases were reported.

Conclusions

The efficacy and safety findings from this 2-year open-label extension study are comparable to and confirm the results of other clinical trials of natalizumab conducted in non-Asian patient populations, and provide longer-term evidence of efficacy and safety in Japanese patients.

Trial registration

ClinicalTrials.gov identifier NCT01416155.

Funding

Biogen.
Literature
1.
Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910.CrossRefPubMed
2.
Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):911–23.CrossRefPubMed
3.
O’Connor P, Goodman A, Kappos L, Lublin F, Polman C, Rudick RA, et al. Long-term safety and effectiveness of natalizumab redosing and treatment in the STRATA MS Study. Neurology. 2014;83(1):78–86.CrossRefPubMedPubMedCentral
4.
Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, et al. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry. 2014;85(11):1190–7.CrossRefPubMedPubMedCentral
5.
Kallweit U, Jelcic I, Braun N, Fischer H, Zörner B, Schreiner B, et al. Sustained efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis independent of disease activity and disability at baseline: real-life data from a Swiss cohort. Clin Neuropharmacol. 2012;35(2):77–80.CrossRefPubMed
6.
Putzki N, Yaldizli O, Bühler R, Schwegler G, Curtius D, Tettenborn B. Natalizumab reduces clinical and MRI activity in multiple sclerosis patients with high disease activity: results from a multicenter study in Switzerland. Eur Neurol. 2010;63(2):101–6.CrossRefPubMed
7.
Sangalli F, Moiola L, Bucello S, Annovazzi P, Rizzo A, Radaelli M, et al. Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study. Neurol Sci. 2011;31(Suppl 3):299–302.CrossRefPubMed
8.
Saida T, Kira J-I, Kishida S, Yamamura T, Sudo Y, Ogiwara K, et al. Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: a double-blind, randomized controlled trial and open-label pharmacokinetic study. Mult Scler Relat Disord. 2016 (Epub ahead of print).
9.
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.CrossRefPubMedPubMedCentral
10.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444–52.CrossRefPubMed
11.
Sorensen PS, Jensen PE, Haghikia A, Lundkvist M, Vedeler C, Sellebjerg F, et al. Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab. Mult Scler. 2011;17(9):1074–8.CrossRefPubMed
12.
Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010;68(3):295–303.CrossRefPubMed
13.
Lee P, Plavina T, Castro A, Berman M, Jaiswal D, Rivas S, et al. A second-generation ELISA (STRATIFY JCV™ DxSelect™) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol Off Publ Pan Am Soc Clin Virol. 2013;57(2):141–6.CrossRef
14.
Tysabri (natalizumab). Summary of product characteristics. Cambridge: Biogen; 2016.
15.
Calabresi PA, Giovannoni G, Confavreux C, Galetta SL, Havrdova E, Hutchinson M, et al. The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL. Neurology. 2007;69(14):1391–403.CrossRefPubMed
16.
Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.CrossRefPubMed
17.
Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348(1):15–23.CrossRefPubMed
Metadata
Title
Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial
Authors
Takahiko Saida
Jun-Ichi Kira
Shuji Kishida
Takashi Yamamura
Nobuhisa Ohtsuka
Yan Ling
Shinichi Torii
Nisha Lucas
Geoffrey Kuesters
Deb Steiner
J. T. Tibung
on behalf of the Natalizumab Trial Principal Investigators
Publication date
01-06-2017
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue 1/2017
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-016-0059-z

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