Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study

Jai Perumal; Roumen Balabanov; Ray Su; Roger Chang; Laura Balcer; Steven Galetta; Denise I. Campagnolo; Robin Avila; Lily Lee; Danette Rutledge; Robert J. Fox

doi:10.1007/s12325-021-01722-w

Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study

Jai Perumal^*, Roumen Balabanov, Ray Su, Roger Chang, Laura Balcer, Steven Galetta, Denise I. Campagnolo, Robin Avila, Lily Lee, Danette Rutledge, Robert J. Fox

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration: ClinicalTrials.gov identifier NCT01485003.

Original language	English (US)
Pages (from-to)	3724-3742
Number of pages	19
Journal	Advances in Therapy
Volume	38
Issue number	7
DOIs	https://doi.org/10.1007/s12325-021-01722-w
State	Published - Jul 2021

Funding

The authors gratefully acknowledge the STRIVE investigators, listed below, for their efforts and contributions, as well as the patients. STRIVE investigators: Bridget Bagert, MD, Roumen Balabanov, MD, Margaret Burnett, MD, Claudia Chaves, MD, Stanley Cohan, MD, PhD, Joanna Cooper, MD, Eric Eggenberger, DO, John Foley, MD, Edward Fox, MD, PhD, Robert Fox, MD, Dennis Garwacki, MD, Lawrence Goldstick, MD, Benjamin Greenberg, MD, MHS, Mark Gudesblatt, MD, Craig Herrman, MD, Jonathan Howard, MD, John Huddlestone, MD, Mark Janicki, MD, Jeffrey Kaplan, MD, George Katsamakis, MD, Amos Katz, MD, Mariko Kita, MD, Lauren Krupp, MD, Ellen Lathi, MD, Kermit Lloyd, MD, Kenneth Mankowski, DO, Tamara Miller, MD, Stephen Newman, MD, Scott Newsome, DO, Allan Perel, MD, Jai Perumal, MD, John Puente, MD, Marcus Rice, MD, Emily Riser, MD, Peter Riskind, MD, PhD, Teri Schreiner, MD, MPH, Christopher Sheppard, MD, Scott Silliman, MD, Jason Silversteen, DO, Jacob Sloane, MD, PhD, Charles Smith, MD, Ben Thrower, MD, Robert Tillett, MD, Carlo Tornatore, MD. Biogen provided funding for this study as well as funding for medical writing support in the development of this manuscript. Biogen also funded the journal’s Rapid Service and Open Access Fees for this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Jai Perumal, Roumen Balabanov, Laura Balcer, Steve Galetta, Denise I. Campagnolo, and Robert J. Fox were involved in the conception and design of the study. Ray Su and Roger Chang performed the statistical analyses. All authors were involved in drafting the manuscript, discussing the results, and providing critical revision of the article. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D’Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Portions of these results were presented at the European Committee for Treatment & Research in Multiple Sclerosis (ECTRIMS; September 11–13, 2019; Stockholm, Sweden). Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis. All patients provided written informed consent prior to enrollment. Approval was granted by the Copernicus Group IRB #1 (reference number IRB00001313) and, at the rest of the study sites, by an independent ethics committee (Supplementary Appendix S1). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. The datasets generated and/or analyzed during the current study are not publicly available. The authors fully support sharing whenever possible. Requests for de-identified data should be made to Biogen via established company data-sharing policies and processes detailed on the website http://clinicalresearch.biogen.com/. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D’Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis.

Keywords

Anti-JCV antibody negative
Magnetic resonance imaging
Natalizumab
No evidence of disease activity
Relapsing-remitting multiple sclerosis

ASJC Scopus subject areas

Pharmacology (medical)

Access to Document

10.1007/s12325-021-01722-w

Cite this

@article{57a1d3b89f344b0a87eab5cc65b0824a,

title = "Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study",

abstract = "Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration: ClinicalTrials.gov identifier NCT01485003.",

keywords = "Anti-JCV antibody negative, Magnetic resonance imaging, Natalizumab, No evidence of disease activity, Relapsing-remitting multiple sclerosis",

author = "Jai Perumal and Roumen Balabanov and Ray Su and Roger Chang and Laura Balcer and Steven Galetta and Campagnolo, {Denise I.} and Robin Avila and Lily Lee and Danette Rutledge and Fox, {Robert J.}",

note = "Funding Information: The authors gratefully acknowledge the STRIVE investigators, listed below, for their efforts and contributions, as well as the patients. STRIVE investigators: Bridget Bagert, MD, Roumen Balabanov, MD, Margaret Burnett, MD, Claudia Chaves, MD, Stanley Cohan, MD, PhD, Joanna Cooper, MD, Eric Eggenberger, DO, John Foley, MD, Edward Fox, MD, PhD, Robert Fox, MD, Dennis Garwacki, MD, Lawrence Goldstick, MD, Benjamin Greenberg, MD, MHS, Mark Gudesblatt, MD, Craig Herrman, MD, Jonathan Howard, MD, John Huddlestone, MD, Mark Janicki, MD, Jeffrey Kaplan, MD, George Katsamakis, MD, Amos Katz, MD, Mariko Kita, MD, Lauren Krupp, MD, Ellen Lathi, MD, Kermit Lloyd, MD, Kenneth Mankowski, DO, Tamara Miller, MD, Stephen Newman, MD, Scott Newsome, DO, Allan Perel, MD, Jai Perumal, MD, John Puente, MD, Marcus Rice, MD, Emily Riser, MD, Peter Riskind, MD, PhD, Teri Schreiner, MD, MPH, Christopher Sheppard, MD, Scott Silliman, MD, Jason Silversteen, DO, Jacob Sloane, MD, PhD, Charles Smith, MD, Ben Thrower, MD, Robert Tillett, MD, Carlo Tornatore, MD. Biogen provided funding for this study as well as funding for medical writing support in the development of this manuscript. Biogen also funded the journal{\textquoteright}s Rapid Service and Open Access Fees for this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Jai Perumal, Roumen Balabanov, Laura Balcer, Steve Galetta, Denise I. Campagnolo, and Robert J. Fox were involved in the conception and design of the study. Ray Su and Roger Chang performed the statistical analyses. All authors were involved in drafting the manuscript, discussing the results, and providing critical revision of the article. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D{\textquoteright}Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Portions of these results were presented at the European Committee for Treatment & Research in Multiple Sclerosis (ECTRIMS; September 11–13, 2019; Stockholm, Sweden). Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis. All patients provided written informed consent prior to enrollment. Approval was granted by the Copernicus Group IRB #1 (reference number IRB00001313) and, at the rest of the study sites, by an independent ethics committee (Supplementary Appendix S1). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. The datasets generated and/or analyzed during the current study are not publicly available. The authors fully support sharing whenever possible. Requests for de-identified data should be made to Biogen via established company data-sharing policies and processes detailed on the website http://clinicalresearch.biogen.com/. Funding Information: Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D{\textquoteright}Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Funding Information: Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jul,

doi = "10.1007/s12325-021-01722-w",

language = "English (US)",

volume = "38",

pages = "3724--3742",

journal = "Advances in Therapy",

issn = "0741-238X",

publisher = "Adis",

number = "7",

}

TY - JOUR

T1 - Natalizumab in Early Relapsing-Remitting Multiple Sclerosis

T2 - A 4-Year, Open-Label Study

AU - Perumal, Jai

AU - Balabanov, Roumen

AU - Su, Ray

AU - Chang, Roger

AU - Balcer, Laura

AU - Galetta, Steven

AU - Campagnolo, Denise I.

AU - Avila, Robin

AU - Lee, Lily

AU - Rutledge, Danette

AU - Fox, Robert J.

N1 - Funding Information: The authors gratefully acknowledge the STRIVE investigators, listed below, for their efforts and contributions, as well as the patients. STRIVE investigators: Bridget Bagert, MD, Roumen Balabanov, MD, Margaret Burnett, MD, Claudia Chaves, MD, Stanley Cohan, MD, PhD, Joanna Cooper, MD, Eric Eggenberger, DO, John Foley, MD, Edward Fox, MD, PhD, Robert Fox, MD, Dennis Garwacki, MD, Lawrence Goldstick, MD, Benjamin Greenberg, MD, MHS, Mark Gudesblatt, MD, Craig Herrman, MD, Jonathan Howard, MD, John Huddlestone, MD, Mark Janicki, MD, Jeffrey Kaplan, MD, George Katsamakis, MD, Amos Katz, MD, Mariko Kita, MD, Lauren Krupp, MD, Ellen Lathi, MD, Kermit Lloyd, MD, Kenneth Mankowski, DO, Tamara Miller, MD, Stephen Newman, MD, Scott Newsome, DO, Allan Perel, MD, Jai Perumal, MD, John Puente, MD, Marcus Rice, MD, Emily Riser, MD, Peter Riskind, MD, PhD, Teri Schreiner, MD, MPH, Christopher Sheppard, MD, Scott Silliman, MD, Jason Silversteen, DO, Jacob Sloane, MD, PhD, Charles Smith, MD, Ben Thrower, MD, Robert Tillett, MD, Carlo Tornatore, MD. Biogen provided funding for this study as well as funding for medical writing support in the development of this manuscript. Biogen also funded the journal’s Rapid Service and Open Access Fees for this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Jai Perumal, Roumen Balabanov, Laura Balcer, Steve Galetta, Denise I. Campagnolo, and Robert J. Fox were involved in the conception and design of the study. Ray Su and Roger Chang performed the statistical analyses. All authors were involved in drafting the manuscript, discussing the results, and providing critical revision of the article. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D’Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Portions of these results were presented at the European Committee for Treatment & Research in Multiple Sclerosis (ECTRIMS; September 11–13, 2019; Stockholm, Sweden). Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis. All patients provided written informed consent prior to enrollment. Approval was granted by the Copernicus Group IRB #1 (reference number IRB00001313) and, at the rest of the study sites, by an independent ethics committee (Supplementary Appendix S1). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. The datasets generated and/or analyzed during the current study are not publicly available. The authors fully support sharing whenever possible. Requests for de-identified data should be made to Biogen via established company data-sharing policies and processes detailed on the website http://clinicalresearch.biogen.com/. Funding Information: Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Alexandra D’Agostino, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by Biogen. Funding Information: Jai Perumal has received fees from Acorda, Biogen, Genzyme, and Teva. Roumen Balabanov has received consulting fees from Biogen, Sanofi, and Teva and grant/research support from Biogen. Ray Su was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; he is now an employee of Inari Medical, which was not involved in this study. Lily Lee was an employee of Biogen at the time of these analyses and may hold stock and/or stock options in Biogen; she is now an employee of TG Therapeutics, which was not involved in this study. Laura Balcer has received consulting fees from Biogen and Genzyme. Steven Galetta has received consulting fees from Biogen. Roger Chang, Denise I. Campagnolo, Robin Avila, and Danette Rutledge are employees of and may hold stock and/or stock options in Biogen. Robert J. Fox has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi, Teva, and TG Therapeutics; has served on advisory committees for Actelion, Biogen, and Novartis; and has received clinical trial contract and research grant funding from Biogen and Novartis. Publisher Copyright: © 2021, The Author(s).

PY - 2021/7

Y1 - 2021/7

N2 - Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration: ClinicalTrials.gov identifier NCT01485003.

AB - Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. Results: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7–63.4%) and 73.6% (95% CI 66.2–80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0–89.9%) and 91.9% (95% CI 86.4–95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54–9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15–0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05–0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. Conclusion: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. Trial Registration: ClinicalTrials.gov identifier NCT01485003.

KW - Anti-JCV antibody negative

KW - Magnetic resonance imaging

KW - Natalizumab

KW - No evidence of disease activity

KW - Relapsing-remitting multiple sclerosis

UR - http://www.scopus.com/inward/record.url?scp=85106212226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85106212226&partnerID=8YFLogxK

U2 - 10.1007/s12325-021-01722-w

DO - 10.1007/s12325-021-01722-w

M3 - Article

C2 - 34014549

AN - SCOPUS:85106212226

SN - 0741-238X

VL - 38

SP - 3724

EP - 3742

JO - Advances in Therapy

JF - Advances in Therapy

IS - 7

ER -

Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study

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