Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

Gavin Giovannoni; Jeffrey A Cohen; Alasdair J Coles; Hans-Peter Hartung; Eva Havrdova; Krzysztof W Selmaj; David H Margolin; Stephen L Lake; Susan M Kaup; Michael A Panzara; D Alastair S Compston; CARE-MS II Investigators; Per Soelberg Sørensen

doi:10.1212/WNL.0000000000003319

Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

Gavin Giovannoni, Jeffrey A Cohen, Alasdair J Coles, Hans-Peter Hartung, Eva Havrdova, Krzysztof W Selmaj, David H Margolin, Stephen L Lake, Susan M Kaup, Michael A Panzara, D Alastair S Compston, CARE-MS II Investigators, Per Soelberg Sørensen (Medlem af forfattergruppering)

Afdeling for Hjerne- og Nervesygdomme

54 Citationer (Scopus)

Abstract

OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.

METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.

RESULTS: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.

CONCLUSIONS: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.

Originalsprog	Engelsk
Tidsskrift	Neurology
Vol/bind	87
Udgave nummer	19
Sider (fra-til)	1985-1992
Antal sider	8
ISSN	0028-3878
DOI	https://doi.org/10.1212/WNL.0000000000003319
Status	Udgivet - 8 nov. 2016

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10.1212/WNL.0000000000003319

Citationsformater

Giovannoni, G., Cohen, J. A., Coles, A. J., Hartung, H.-P., Havrdova, E., Selmaj, K. W., Margolin, D. H., Lake, S. L., Kaup, S. M., Panzara, M. A., Compston, D. A. S., CARE-MS II Investigators, & Sørensen, P. S. (2016). Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology, 87(19), 1985-1992. https://doi.org/10.1212/WNL.0000000000003319

@article{ab56707b50ec4908b158d4881832849e,

title = "Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients",

abstract = "OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.RESULTS: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.CONCLUSIONS: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.",

author = "Gavin Giovannoni and Cohen, {Jeffrey A} and Coles, {Alasdair J} and Hans-Peter Hartung and Eva Havrdova and Selmaj, {Krzysztof W} and Margolin, {David H} and Lake, {Stephen L} and Kaup, {Susan M} and Panzara, {Michael A} and Compston, {D Alastair S} and {CARE-MS II Investigators} and S{\o}rensen, {Per Soelberg}",

note = "{\textcopyright} 2016 American Academy of Neurology.",

year = "2016",

month = nov,

day = "8",

doi = "10.1212/WNL.0000000000003319",

language = "English",

volume = "87",

pages = "1985--1992",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "19",

}

TY - JOUR

T1 - Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

AU - Giovannoni, Gavin

AU - Cohen, Jeffrey A

AU - Coles, Alasdair J

AU - Hartung, Hans-Peter

AU - Havrdova, Eva

AU - Selmaj, Krzysztof W

AU - Margolin, David H

AU - Lake, Stephen L

AU - Kaup, Susan M

AU - Panzara, Michael A

AU - Compston, D Alastair S

AU - CARE-MS II Investigators

A2 - Sørensen, Per Soelberg

PY - 2016/11/8

Y1 - 2016/11/8

N2 - OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.RESULTS: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.CONCLUSIONS: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.

AB - OBJECTIVE: To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy.METHODS: Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation.RESULTS: Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients.CONCLUSIONS: In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.

U2 - 10.1212/WNL.0000000000003319

DO - 10.1212/WNL.0000000000003319

M3 - Journal article

C2 - 27733571

SN - 0028-3878

VL - 87

SP - 1985

EP - 1992

JO - Neurology

JF - Neurology

IS - 19

ER -

Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients

Abstract

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