Efficacy and Safety of Natalizumab in Multiple Sclerosis: Interim Observational Programme Results

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2014 Feb 18

PMID 24532785

Citations 67

Authors

Helmut Butzkueven

Ludwig Kappos

Fabio Pellegrini

Maria Trojano

Heinz Wiendl

Radhika N Patel

Annie Zhang

Christophe Hotermans

Shibeshih Belachew

Affiliations

Soon will be listed here.

Abstract

Background: Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.

Objective: To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.

Results: In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11-44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.

Conclusions: Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.

Trial Registration Number: NCT00493298.

Citing Articles

Monoclonal antibodies in neuro-ophthalmology.

Keehn C, Yazdian A, Hunt P, Davila-Siliezar P, Laylani N, Lee A Saudi J Ophthalmol. 2024; 38(1):13-24.

PMID: 38628411 PMC: 11017005. DOI: 10.4103/sjopt.sjopt_256_23.

Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis.

Rindi L, Zace D, Braccialarghe N, Massa B, Barchi V, Iannazzo R Drug Saf. 2024; 47(4):333-354.

PMID: 38321317 DOI: 10.1007/s40264-023-01383-4.

Identification and tracking of HTLV-1-infected T cell clones in virus-associated neurologic disease.

Nozuma S, Matsuura E, Tanaka M, Kodama D, Matsuzaki T, Yoshimura A JCI Insight. 2023; 8(7).

PMID: 37036006 PMC: 10132145. DOI: 10.1172/jci.insight.167422.

Correction to: Improvements in Cognitive Processing Speed, Disability, and Patient‑Reported Outcomes in Patients with Early Relapsing‑Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4‑year, Real‑World, Open‑Label Study.

Perumal J, Balabanov R, Su R, Chang R, Balcer L, Galetta S CNS Drugs. 2023; 37(3):275-289.

PMID: 36780107 PMC: 10024661. DOI: 10.1007/s40263-022-00982-6.

Correlation of disability with quality of life in patients with multiple sclerosis treated with natalizumab: primary results and post hoc analysis of the TYSabri ImPROvement study (PROTYS).

Achtnichts L, Zecca C, Findling O, Kamm C, Mueller S, Kuhle J BMJ Neurol Open. 2023; 5(1):e000304.

PMID: 36727105 PMC: 9884862. DOI: 10.1136/bmjno-2022-000304.

References

Polman C, OConnor P, Havrdova E, Hutchinson M, Kappos L, Miller D . A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9):899-910. DOI: 10.1056/NEJMoa044397. View

Rudick R, Sandrock A . Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS. Expert Rev Neurother. 2005; 4(4):571-80. DOI: 10.1586/14737175.4.4.571. View

Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A . Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012; 366(20):1870-80. DOI: 10.1056/NEJMoa1107829. View

Kallweit U, Jelcic I, Braun N, Fischer H, Zorner B, Schreiner B . 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. DOI: 10.1097/WNF.0b013e31824644e6. View

Roxburgh R, Seaman S, Masterman T, Hensiek A, Sawcer S, Vukusic S . Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005; 64(7):1144-51. DOI: 10.1212/01.WNL.0000156155.19270.F8. View

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh J, Comber H . Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013; 49(6):1374-403. DOI: 10.1016/j.ejca.2012.12.027. View

Kappos L, Bates D, Edan G, Eraksoy M, Garcia-Merino A, Grigoriadis N . Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol. 2011; 10(8):745-58. DOI: 10.1016/S1474-4422(11)70149-1. View

Putzki N, Yaldizli O, Buhler 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. DOI: 10.1159/000276400. View

Rudick R, Stuart W, Calabresi P, Confavreux C, Galetta S, Radue E . Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9):911-23. DOI: 10.1056/NEJMoa044396. View

10.

Sangalli F, Moiola L, Bucello S, Annovazzi P, Rizzo A, Radaelli M . Efficacy and tolerability of natalizumab in relapsing-remitting multiple sclerosis patients: a post-marketing observational study. Neurol Sci. 2010; 31 Suppl 3:299-302. DOI: 10.1007/s10072-010-0344-z. View

11.

Phillips J, Giovannoni G, Lublin F, OConnor P, Polman C, Willoughby E . Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult Scler. 2011; 17(8):970-9. DOI: 10.1177/1352458511399611. View

12.

Hutchinson M, Kappos L, Calabresi P, Confavreux C, Giovannoni G, Galetta S . The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL. J Neurol. 2009; 256(3):405-15. DOI: 10.1007/s00415-009-0093-1. View