Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.

Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial.

Collaborators (229)

Arnold D, Cohen JA, Coles A, Compston A, Confavareux C, Fox E, Hartung HP, Havrdova E, Selmaj K, Weiner H, Panitch H, Clifford D, Antel J, Barkhof F, Snydman D, DeGroot L, Cines D, D'Agostino R, Greenberg B, Krauss J, Limmroth V, Markowitz C, Naismith R, Tabby D, Gupta AS, Fox E, Glyman SA, Thoits TK, Sullivan HC, Cascione MC, Rammohan KW, Gazda SK, Wynn DR, Wray SE, Elias S, Ford CC, Goodman A, Hughes BL, Khan OA, Vaishnav AG, Kirzinger S, Lynch SG, Mattson DH, Braley TJ, Mikol DD, Krieger S, Miller A, Miller TA, Collins F, Riskind PN, Bomprezzi R, Wingerchuk DM, Steingo B, Cohen JA, Crayton HJ, Royal W 3rd, Twyman CL, Cooper JA, Weiner LP, Moses H Jr, Agius MA, Bass AD, Lallana EC, Mitchell GW, Krolczyk SJ, Minagar A, Jubelt B, Evans BK, Hunter SF, Rizvi SA, Sheppard CA, Honeycutt WM, Herbert J, Lathi ES, Pardo G, Ilenson LJ, Rothstein TL, Thrower BW, Picone MA, Kita M, Grazioli EM, Silliman SL, Giancarlo T, Gottesman MH, Zeid NE, Rowe VD 3rd, Boutwell CM, Schaeffer JD, LaGanke CC, Riley CS, Gottschalk C, Preiningerova J, Edwards KR, Wendt JK, Bigley K Jr, Singer BA, Shubin RA, Markovic-Plese S, Jones DE, Clauser G, Freedman MS, Grand'Maison F, Jacques FH, Traboulsee AL, Brunet DG, Kremenchutzky M, Ayotte C, Lava NS, Waldman SR, Janus TJ, Vincent SG, Gudesblatt M, Rossen M, Stein LS, Machanic BI, Vollmer T, Gitt JS, Dunn J, Negroski D, Fletcher MH, Javed A, Frohman EM, Macdonell R, Owen J, Paine MA, Boundy K, Broadley S, Vucic S, Reddel S, Dreyer MD, Schwartz R, McCombe PA, Hodgkinson S, Tilbery C, Ferreira ML, Callegaro D, Martins MM, Villanueva JA, Caballero NS, Mendoza CV, Deri NH, Coles A, Scolding NJ, Giovannoni G, Sharrack B, Rog DJ, Comi G, Ghezzi A, Mancardi GL, Durelli L, Bertolotto A, Capra R, Pozzilli C, Marrosu MG, Hupperts RM, van Munster E, Montalbán X, González RA, Ayuso GI, Fernández ÓF, Haya C, Confavreux C, Vermersch P, de Seze J, Moreau T, Clavelou P, Lubetzki C, Clanet M, Debouverie M, Edan G, Hartung HP, Haas J, Stangel M, Ziemssen T, Hemmer B, Baum K, Zettl UK, Herrlinger U, Köhler W, Ochs G, Oschmann P, Tiel-Wilck K, Tumani H, Urban PP, Lycke J, Svenningsson A, Kovarova I, Vachova M, Rektor I, Talab R, Selmaj K, Stelmasiak Z, Kozubski W, Dubois BD, Dive D, Grandfossé R, Sindic C, Vass K, Sørensen PS, Petersen T, Ravnborg M, Achiron A, Dembinsky AV, Karni A, Gusev EI, Stolyarov ID, Zavalishin IA, Skoromets AA, Boyko AN, Belova AN, Malkova NA, Barantsevich ER, Yakupov EZ, Perfiliev SV, Poverennova IE, Voloshyna NP, Nehrych TI, Kobys TO, Habek M, Brinar V, Trkanjec Z, Vladić A, Piskać SK, Meštrovića I, Antonelli L, Drulović J, Nadj Č, Dinčić E, Tončev G.

Author information

  • 1Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. ajc1020@medschl.cam.ac.uk

Abstract

BACKGROUND:

The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.

METHODS:

In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1:2:2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 μg, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.

FINDINGS:

202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0·51 [95% CI 0·39-0·65]; p<0·0001), corresponding to a 49·4% improvement with alemtuzumab. 94 (47%) patients in the interferon beta 1a group were relapse-free at 2 years compared with 278 (65%) patients in the alemtuzumab group (p<0·0001). 40 (20%) patients in the interferon beta 1a group had sustained accumulation of disability compared with 54 (13%) in the alemtuzumab group (hazard ratio 0·58 [95% CI 0·38-0·87]; p=0·008), corresponding to a 42% improvement in the alemtuzumab group. For 435 patients allocated alemtuzumab 12 mg, 393 (90%) had infusion-associated reactions, 334 (77%) had infections (compared with 134 [66%] of 202 patients in the interferon beta 1a group) that were mostly mild-moderate with none fatal, 69 (16%) had thyroid disorders, and three (1%) had immune thrombocytopenia.

INTERPRETATION:

For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. Suitable risk management strategies allow for early identification of alemtuzumab's main adverse effect of secondary autoimmunity.

FUNDING:

Genzyme (Sanofi) and Bayer Schering Pharma.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Comment in

PMID:
23122650
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk