Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial

被引:195
作者
Coles, A. J. [1 ]
Fox, E. [2 ]
Vladic, A. [3 ]
Gazda, S. K. [4 ]
Brinar, V. [5 ,6 ]
Selmaj, K. W. [7 ]
Skoromets, A. [8 ]
Stolyarov, I. [9 ]
Bass, A. [10 ]
Sullivan, H. [11 ]
Margolin, D. H. [12 ]
Lake, S. L. [12 ]
Moran, S. [12 ]
Palmer, J. [12 ]
Smith, M. S. [13 ]
Compston, D. A. S. [1 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Dept Neurosci, Cambridge CB2 2QQ, England
[2] Cent Texas Neurol Consultants, Round Rock, TX USA
[3] Gen Hosp Sv Duh, Zagreb, Croatia
[4] INTEGRA Clin Res, San Antonio, TX USA
[5] Zagreb Med Sch, Zagreb, Croatia
[6] Univ Hosp Ctr, Zagreb, Croatia
[7] Med Univ Lodz, Lodz, Poland
[8] IP Pavlovs State Med Univ, St Petersburg, Russia
[9] Russian Acad Sci, Inst Human Brain, St Petersburg 196140, Russia
[10] Neurol Ctr San Antonio, San Antonio, TX USA
[11] St Marys Hlth Care, Hauenstein Ctr, Grand Rapids, MI USA
[12] Genzyme Corp, Cambridge, MA USA
[13] ReS Pharmaceut Serv Inc, Ft Washington, MD USA
基金
英国医学研究理事会;
关键词
THERAPEUTIC LYMPHOCYTE DEPLETION; MULTIPLE-SCLEROSIS; CAMPATH-1H;
D O I
10.1212/WNL.0b013e31824e8ee7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon beta-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon beta-1a (IFN beta-1a) through extended follow-up (up to 60 months from baseline). Methods: Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFN beta-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months. Results: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFN beta-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFN beta-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFN beta-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFN beta-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFN beta-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFN beta-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab. Conclusions: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFN beta-1a, with a safety profile consistent with previous reports. Classification of Evidence: This study provides Class III evidence that alemtuzumab is more effective than interferon beta-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period. Neurology (R) 2012;78:1069-1078
引用
收藏
页码:1069 / 1078
页数:10
相关论文
共 15 条
  • [1] Anti-glomerular basement membrane disease after alemtuzumab
    Clatworthy, Menna R.
    Wallin, Elizabeth F.
    Jayne, David R.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (07) : 768 - 769
  • [2] The window of therapeutic opportunity in multiple sclerosis
    Coles, AJ
    Cox, A
    Le Page, E
    Jones, J
    Trip, SA
    Deans, J
    Seaman, S
    Miller, DH
    Hale, G
    Waldmann, H
    Compston, DA
    [J]. JOURNAL OF NEUROLOGY, 2006, 253 (01) : 98 - 108
  • [3] Coles AJ, 2008, NEW ENGL J MED, V359, P1786, DOI 10.1056/NEJMoa0802670
  • [4] Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes
    Coles, Alasdair J.
    Fox, Edward
    Vladic, Anton
    Gazda, Suzanne K.
    Brinar, Vesna
    Selmaj, Krzysztof W.
    Doan-Do Bass, Ann
    Wynn, Daniel R.
    Margolin, David H.
    Lake, Stephen L.
    Moran, Susan
    Palmer, Jeffrey
    Smith, M. Shelton
    Compston, D. Alastair S.
    [J]. LANCET NEUROLOGY, 2011, 10 (04) : 338 - 348
  • [5] Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis
    Cox, AL
    Thompson, SAJ
    Jones, JL
    Robertson, VH
    Haley, G
    Waldmann, H
    Compston, DAS
    Coles, AJ
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (11) : 3332 - 3342
  • [6] A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis
    Fox, E. J.
    Sullivan, H. C.
    Gazda, S. K.
    Mayer, L.
    O'Donnell, L.
    Melia, K.
    Lake, S. L.
    [J]. EUROPEAN JOURNAL OF NEUROLOGY, 2012, 19 (02) : 307 - 311
  • [7] The incidence of herpes zoster in a United States administrative database
    Insinga, RP
    Itzler, RF
    Pellissier, JM
    Saddier, P
    Nikas, AA
    [J]. JOURNAL OF GENERAL INTERNAL MEDICINE, 2005, 20 (08) : 748 - 753
  • [8] IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)
    Jones, Joanne L.
    Phuah, Chia-Ling
    Cox, Amanda L.
    Thompson, Sara A.
    Ban, Maria
    Shawcross, Jacqueline
    Walton, Amie
    Sawcer, Stephen J.
    Compston, Alastair
    Coles, Alasdair J.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (07) : 2052 - 2061
  • [9] KURTZKE JF, 1983, NEUROLOGY, V33, P1444, DOI 10.1212/WNL.33.11.1444
  • [10] Management and preparedness for infusion and hypersensitivity reactions
    Lenz, Heinz-Josef
    [J]. ONCOLOGIST, 2007, 12 (05) : 601 - 609