Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: A double-blind, randomized controlled trial and open-label pharmacokinetic study

Abstract

In Japanese RRMS patients, natalizumab treatment every 4 weeks for 24 weeks was well tolerated and reduced the development of new brain lesions and relapses (Funded by Biogen; ClinicalTrials.gov identifier: NCT01440101).

Natalizumab for Achieving Relapse-Free, T1 Gadolinium-Enhancing-Lesion-Free, and T2 Lesion-Free Status in Japanese Multiple Sclerosis Patients: A Phase 2 Trial Subanalysis

“…The current study differs from the AFFIRM trial in that the proportion of patients free from new/newly enlarged T2 lesions in this study was not significantly larger with natalizumab than placebo. In addition, a similar result was observed in changes of mean EDSS score, referentially collected, in both groups (baseline score: placebo 2.05 vs. natalizumab 2.45; and score at 24 weeks: placebo 2.16 vs. natalizumab 2.25) [3]. These may be due, at least in part, to the shorter duration of this study (24 weeks) compared with AFFIRM (2 years) [5].…”

“…Part B was a double-blind study in which 94 patients were randomized to natalizumab 300 mg or placebo every 4 weeks for 24 weeks (Fig. 1) [3]. This subanalysis pertains only to patients randomized in part B of the study.…”

“…This subanalysis pertains only to patients randomized in part B of the study. The methodology of the full study, along with its efficacy and safety data, has been previously published [3].

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“…In both studies, natalizumab reduced the frequency of relapses, mitigated the development of new brain lesions on magnetic resonance imaging (MRI) scans, and delayed the time to confirmed disability worsening relative to placebo. Recently, the results of a phase 2 study of natalizumab in Japanese patients with RRMS were reported, and treatment-related changes in relapses, brain lesions, and disability worsening were comparable to those from the phase 3 studies [3]. …”

Current immunotherapies for multiple sclerosis and neuromyelitis optica spectrum disorders: the similarities and differences

“…Gilenya, 2010 0.5 mg, once a day, po Sphingosin-1 phosphate receptor agonist; induces lymphocytes to enter secondary lymphoid organs [116][117][118] RRMS [119][120][121][122][123][124] , PPMS [125] Teriflunomide Aubagio, 2012 7 or 14 mg, once a day, po Prevents dihydroorotate dehydrogenase activation; suppresses activated T-lymphocyte proliferation [126,127] RRMS [128][129][130][131] Dimethyl fumarate Tecfidera, 2013 240 mg, twice a day, po Th1-Th2 shift, lymphocyte apoptosis [132,133] RRMS [134][135][136] Natalizumab Tysabri, 2006 300 mg, once every 4 weeks, iv Inhibits α4-integrin; prevents activated CD4+ T-cells from crossing the blood-brain barrier [137][138][139] RRMS [140][141][142][143][144][145] , SPMS [146] Alemtuzumab Lemtrada, 2013 12 mg, once a day for 5 days, then for 3 days one year later, iv…”