Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS

Douglas L Arnold, Elizabeth Fisher, Vesna V Brinar, Jeffrey A Cohen, Alasdair J Coles, Gavin Giovannoni, Hans-Peter Hartung, Eva Havrdova, Krzysztof W Selmaj, Miroslav Stojanovic, Howard L Weiner, Stephen L Lake, David H Margolin, David R Thomas, Michael A Panzara, D Alastair S Compston, CARE-MS I and CARE-MS II Investigators, Douglas L Arnold, Elizabeth Fisher, Vesna V Brinar, Jeffrey A Cohen, Alasdair J Coles, Gavin Giovannoni, Hans-Peter Hartung, Eva Havrdova, Krzysztof W Selmaj, Miroslav Stojanovic, Howard L Weiner, Stephen L Lake, David H Margolin, David R Thomas, Michael A Panzara, D Alastair S Compston, CARE-MS I and CARE-MS II Investigators

Abstract

Objective: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS).

Methods: The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II).

Results: Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-β-1a.

Conclusions: Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS.

Clinicaltrialsgov identifier: NCT00530348 and NCT00548405.

Classification of evidence: The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints.

Figures

Figure 1. Percentage of CARE-MS I patients… — **Figure 1. Percentage of CARE-MS I patients free from lesion activity and overall MRI disease activity**
Percentage of patients free from (A) new/enlarging T2-hyperintense lesions, (B) gadolinium (Gd)-enhancing lesions, and (C) new T1-hypointense lesions and (D) free from MRI disease activity. Freedom from MRI disease activity defined as the absence of new Gd-enhancing lesions and new/enlarging T2-hyperintense lesions. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CI = confidence interval; NS = no significant difference; SC IFN-β-1a = subcutaneous interferon β-1a. *p

**Figure 2. Percentage of CARE-MS II patients…**

**Figure 2. Percentage of CARE-MS II patients free from lesion activity and overall MRI disease…**

**Figure 2. Percentage of CARE-MS II patients free from lesion activity and overall MRI disease activity**
Percentage of patients free from (A) new/enlarging T2-hyperintense lesions, (B) gadolinium (Gd)-enhancing lesions, and (C) new T1-hypointense lesions and (D) free from MRI disease activity. Freedom from MRI disease activity defined as the absence of new Gd-enhancing lesions and new/enlarging T2-hyperintense lesions. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CI = confidence interval; SC IFN-β-1a = subcutaneous interferon β-1a. *p < 0.05; **p ≤ 0.0001.

**Figure 3. Median percentage change in T2-hyperintense…**

**Figure 3. Median percentage change in T2-hyperintense and T1-hypointense lesion volume in CARE-MS I and…**

**Figure 3. Median percentage change in T2-hyperintense and T1-hypointense lesion volume in CARE-MS I and CARE-MS II**
Median percentage change from baseline in T2-hyperintense lesion volume in (A) CARE-MS I and (B) CARE-MS II. Median percentage change from baseline in T1-hypointense lesion volume in (C) CARE-MS I and (D) CARE-MS II. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; NS = no significant difference; SC IFN-β-1a = subcutaneous interferon β-1a. *p < 0.05.

**Figure 4. Median percentage change in brain…**

**Figure 4. Median percentage change in brain parenchymal fraction in (A) CARE-MS I and (B)…**

**Figure 4. Median percentage change in brain parenchymal fraction in (A) CARE-MS I and (B) CARE-MS II**
Data are shown as medians with standard error bars; p values are for the comparison of alemtuzumab with SC IFN-β-1a over the time period shown. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; NS = no significant difference; SC IFN-β-1a = subcutaneous interferon β-1a.

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Figure 2. Percentage of CARE-MS II patients… — **Figure 2. Percentage of CARE-MS II patients free from lesion activity and overall MRI disease activity**
Percentage of patients free from (A) new/enlarging T2-hyperintense lesions, (B) gadolinium (Gd)-enhancing lesions, and (C) new T1-hypointense lesions and (D) free from MRI disease activity. Freedom from MRI disease activity defined as the absence of new Gd-enhancing lesions and new/enlarging T2-hyperintense lesions. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CI = confidence interval; SC IFN-β-1a = subcutaneous interferon β-1a. *p < 0.05; **p ≤ 0.0001.

Figure 3. Median percentage change in T2-hyperintense… — **Figure 3. Median percentage change in T2-hyperintense and T1-hypointense lesion volume in CARE-MS I and CARE-MS II**
Median percentage change from baseline in T2-hyperintense lesion volume in (A) CARE-MS I and (B) CARE-MS II. Median percentage change from baseline in T1-hypointense lesion volume in (C) CARE-MS I and (D) CARE-MS II. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; NS = no significant difference; SC IFN-β-1a = subcutaneous interferon β-1a. *p < 0.05.

Figure 4. Median percentage change in brain… — **Figure 4. Median percentage change in brain parenchymal fraction in (A) CARE-MS I and (B) CARE-MS II**
Data are shown as medians with standard error bars; p values are for the comparison of alemtuzumab with SC IFN-β-1a over the time period shown. CARE-MS = Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; NS = no significant difference; SC IFN-β-1a = subcutaneous interferon β-1a.

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Source: PubMed

Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS

Abstract

Figures

References

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