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Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients
Gavin Giovannoni, MD, PhD, Jeffrey A. Cohen, MD, Alasdair J. Coles, MD, PhD, Hans-Peter Hartung, MD, PhD, Eva Havrdova, MD, PhD, Krzysztof W. Selmaj, MD, PhD, David H. Margolin, MD, PhD, Stephen L. Lake, ScD, Susan M. Kaup, PhD, MBA, Michael A. Panzara, MD, MPH and D. Alastair S. Compston, MD, PhD On behalf of the CARE-MS II Investigators
Published online before print October 12, 2016, doi: http://dx.doi.org/10.1212/WNL.0000000000003319
Neurology 10.1212/WNL.0000000000003319
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.
Received June 2, 2015.
Accepted in final form July 7, 2016.
© 2016 American Academy of Neurology
Gavin Giovannoni, MD, PhD, Jeffrey A. Cohen, MD, Alasdair J. Coles, MD, PhD, Hans-Peter Hartung, MD, PhD, Eva Havrdova, MD, PhD, Krzysztof W. Selmaj, MD, PhD, David H. Margolin, MD, PhD, Stephen L. Lake, ScD, Susan M. Kaup, PhD, MBA, Michael A. Panzara, MD, MPH and D. Alastair S. Compston, MD, PhD On behalf of the CARE-MS II Investigators
Published online before print October 12, 2016, doi: http://dx.doi.org/10.1212/WNL.0000000000003319
Neurology 10.1212/WNL.0000000000003319
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.
Received June 2, 2015.
Accepted in final form July 7, 2016.
© 2016 American Academy of Neurology