Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial
Abstract
Background The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial.Methods In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis. Eligible participants were randomly allocated in a 2:1 ratio by an interactive voice response system, stratified by site, to receive intravenous alemtuzumab 12 mg per day or subcutaneous interferon beta 1a 44 μg. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and once per day for 3 days at 12 months. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00530348.Findings 187 (96%) of 195 patients randomly allocated interferon beta 1a and 376 (97%) of 386 patients randomly allocated alemtuzumab were included in the primary analyses. 75 (40%) patients in the interferon beta 1a group relapsed (122 events) compared with 82 (22%) patients in the alemtuzumab group (119 events; rate ratio 0·45 [95% CI 0·32-0·63]; p<0.0001), corresponding to a 54·9% improvement with alemtuzumab. Based on Kaplan-Meier estimates, 59% of patients in the interferon beta 1a group were relapse-free at 2 years compared with 78% of patients in the alemtuzumab group (p<0·0001). 20 (11%) of patients in the interferon beta 1a group had sustained accumulation of disability compared with 30 (8%) in the alemtuzumab group (hazard ratio 0·70 [95% CI 0·40-1·23]; p=0·22). 338 (90%) of patients in the alemtuzumab group had infusion-associated reactions; 12 (3%) of which were regarded as serious. Infections, predominantly of mild or moderate severity, occurred in 253 (67%) patients treated with alemtuzumab versus 85 (45%) patients treated with interferon beta 1a. 62 (16%) patients treated with alemtuzumab had herpes infections (predominantly cutaneous) compared with three (2%) patients treated with interferon beta 1a. By 24 months, 68 (18%) patients in the alemtuzumab group had thyroid-associated adverse events compared with 12 (6%) in the interferon beta 1a group, and three (1%) had immune thrombocytopenia compared with none in the interferon beta 1a group. Two patients in the alemtuzumab group developed thyroid papillary carcinoma.Interpretation Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here.Funding Genzyme (Sanofi) and Bayer Schering Pharma.
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In phase III clinical trials comparing alemtuzumab with interferon β-1a in highly active MS, no overall increase in malignancy was observed.
“In the phase III clinical trials comparing alemtuzumab with interferon β-1a in highly active MS, no overall increase in malignancy was observed;”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [60]
Papillary thyroid cancer was discovered in 0.4% of alemtuzumab-treated patients in those trials.
“however, papillary thyroid cancer was discovered in 0.4% of alemtuzumab-treated patients [59, 60].”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [60]
Cites
Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS)
Kurtzke, J. F. (1983) · Neurology · doi:10.1212/wnl.33.11.1444 · Cited by 15,011 · see citing works
Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”
Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H., Kappos, L., Lublin, F. D., Metz, L. M., McFarland, H. F., O'Connor, P. W., et al. (2005) · Annals of Neurology · doi:10.1002/ana.20703 · Cited by 5,017 · see citing works
Self-citationThe Robust Inference for the Cox Proportional Hazards Model
Lin, D. Y., & Wei, L. J. (1989) · Journal of the American Statistical Association · doi:10.1080/01621459.1989.10478874 · Cited by 2,655 · see citing works
Multiple Comparison Procedures
Hochberg, Y., & Tamhane, A. C. (1987) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316672 · Cited by 2,389 · see citing works
Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis
Cohen, J. A., Barkhof, F., Comı, G., Hartung, H., Khatri, B. O., Montalbán, X., Pelletier, J., Capra, R., Gallo, P., Izquierdo, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907839 · Cited by 2,199 · see citing works
Self-citationMultiple Comparison Procedures
Hahs-Vaughn, D., & Lomax, R. (2013) · Routledge eBooks · doi:10.4324/9780203137819-17 · Cited by 2,132 · see citing works
Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis
Rudick, R. A., Stuart, W. H., Calabresi, P. A., Confavreux, C., Galetta, S. L., Radue, E. W., LUBLIN, F. D., Weinstock‐Guttman, B., Wynn, D. R., Lynn, F., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa044396 · Cited by 1,342 · see citing works
Self-citationDiagnostic criteria for multiple sclerosis
Poser, C. M., & Brinar, V. V. (2001) · Clinical Neurology and Neurosurgery · doi:10.1016/s0303-8467(00)00125-6 · Cited by 1,282 · see citing works
Self-citationColes, A. J., Twyman, C. L., Arnold, D. L., Cohen, J. A., Confavreux, C., Fox, E. J., Hartung, H.-P., Havrdova, E., Selmaj, K. W., Weiner, H. L., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61768-1 · Cited by 1,198 · see citing works
Self-citationDevelopment of a multiple sclerosis functional composite as a clinical trial outcome measure
Cutter, G. (1999) · Brain · doi:10.1093/brain/122.5.871 · Cited by 1,191 · see citing works
Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis
The CAMMS Trial Investigators (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802670 · Cited by 1,012 · see citing works
Semiparametric regression for the mean and rate functions of recurrent events
Lin, D. Y., Wei, L. J., Yang, I., & Ying, Z. (2000) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/1467-9868.00259 · Cited by 969 · see citing works
Randomized, comparative study of interferon β-1a treatment regimens in MS
PANITCH, H. S., Goodin, D. S., Francis, G., Chang, P., Coyle, P. K., O'Connor, P. W., Ed, M., Li, D., & Weinshenker, B. G. (2002) · Neurology · doi:10.1212/01.wnl.0000034080.43681.da · Cited by 631 · see citing works
The window of therapeutic opportunity in multiple sclerosis
Coles, A. J., Cox, A., Page, E. L., Jones, J., Trip, S. A., Deans, J., Seaman, S. R., Miller, D. H., Hale, G., Waldmann, H., et al. (2005) · Journal of Neurology · doi:10.1007/s00415-005-0934-5 · Cited by 506 · see citing works
Self-citationKappos, L., Freedman, M. S., Polman, C. H., Edan, G., Hartung, H., Miller, D. H., Montalbán, X., Barkhof, F., Radue, E. W., Bauer, L., et al. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61194-5 · Cited by 500 · see citing works
Self-citationMikol, D. D., Barkhof, F., Chang, P., Coyle, P. K., Jeffery, D., Schwid, S. R., Stubinski, B., & Uitdehaag, B. M. J. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70200-x · Cited by 484 · see citing works
O'Connor, P. W., Filippi, M., Arnason, B. G. W., Comı, G., Cook, S. D., Goodin, D. S., Hartung, H.-P., Jeffery, D., Kappos, L., Boateng, F., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70226-1 · Cited by 404 · see citing works
Self-citationClark, R. A., Watanabe, R., Teague, J. E., Schlapbach, C., Tawa, M. C., Adams, N., Dorosario, A. A., Chaney, K. S., Cutler, C. S., LeBoeuf, N. R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003008 · Cited by 367 · see citing works
Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model
Hu, Y., Turner, M. J., Shields, J. D., Gale, M. S., Hutto, E. H., Roberts, B., Siders, W., & Kaplan, J. M. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03115.x · Cited by 336 · see citing works
Two-Sample Asymptotically Distribution-Free Tests for Incomplete Multivariate Observations
Wei, L., & Lachin, J. M. (1984) · Journal of the American Statistical Association · doi:10.1080/01621459.1984.10478093 · Cited by 307 · see citing works
Jones, J., Phuah, C., Cox, A. L., Thompson, S. A. J., Ban, M., Shawcross, J., Walton, A., Sawcer, S. J., Compston, A., & Coles, A. J. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37878 · Cited by 297 · see citing works
Self-citationLymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis
Cox, A. L., Thompson, S. A. J., Jones, J., Robertson, V. H., Hale, G., Waldmann, H., Compston, D. A. S., & Coles, A. J. (2005) · European Journal of Immunology · doi:10.1002/eji.200535075 · Cited by 291 · see citing works
Self-citationAlemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial
Coles, A. J., Fox, E., Vladić, A., Gazda, S. K., Brinar, V. V., Selmaj, K. W., Skoromets, A. A., Stolyarov, I. D., Bass, A. D.-D., Sullivan, H., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31824e8ee7 · Cited by 266 · see citing works
Self-citationB-Cell Reconstitution and BAFF After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
Thompson, S. A. J., Jones, J., Cox, A. L., Compston, D. A. S., & Coles, A. J. (2009) · Journal of Clinical Immunology · doi:10.1007/s10875-009-9327-3 · Cited by 230 · see citing works
Self-citationA randomized, double-blind, dose-comparison study of weekly interferon β-1a in relapsing MS
Clanet, M., Radue, E. W., Kappos, L., Hartung, H., Hohlfeld, R., Sandberg‐Wollheim, M., Kooijmans-Coutinho, M. F., Tsao, E., Sandrock, A., & the European IFNβ-1a (Avonex) Dose-Comparison Study Investigators* (2002) · Neurology · doi:10.1212/01.wnl.0000032256.35561.d6 · Cited by 219 · see citing works
Self-citationMoreau, T., Scolding, N. J., Compston, A., Thorpe, J. W., Miller, D., MOSELEY, I. F., Hale, G., Waldmann, H., Clayton, D. G., Wing, M. G., et al. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91339-0 · Cited by 186 · see citing works
Use of the Multiple Sclerosis Functional Composite as an Outcome Measure in a Phase 3 Clinical Trial
Cohen, J. A. (2001) · Archives of Neurology · doi:10.1001/archneur.58.6.961 · Cited by 177 · see citing works
Self-citationAnıl, C., Göksel, S., & Gürsoy, A. (2010) · Thyroid · doi:10.1089/thy.2009.0450 · Cited by 142 · see citing works
Multicentre study of thyroid nodules in patients with Graves' disease
Kraimps, J. L., Bouin-Pineau, M. H., Mathonnet, M., de Calan, L., Ronceray, J., Visset, J., Maréchaud, R., & Barbier, J. (2000) · British journal of surgery · doi:10.1046/j.1365-2168.2000.01504.x · Cited by 123 · see citing works
Ultrasonographic screening for detection of thyroid cancer in patients with Graves’ disease
Kim, W. B., Han, S., Kim, T. Y., Nam‐Goong, I. S., Gong, G., Lee, H. K., Hong, S. J., & Shong, Y. K. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02043.x · Cited by 103 · see citing works
Lachin, J. M. (1992) · Statistics in Medicine · doi:10.1002/sim.4780110903 · Cited by 100 · see citing works
Kinkel, R. P. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.1426 · Cited by 97 · see citing works
Phase III dose‐comparison study of glatiramer acetate for multiple sclerosis
Comi, G., Cohen, J. A., Arnold, D. L., Wynn, D. R., Filippi, M., & for the FORTE Study Group (2010) · Annals of Neurology · doi:10.1002/ana.22316 · Cited by 73 · see citing works
Self-citationStatistical methods for the analysis of relapse data in MS clinical trials
Wang, Y. C., Meyerson, L. J., Tang, Y., & Qian, N. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.07.017 · Cited by 59 · see citing works
Berker, D. S., Işık, S., Özuğuz, U., Tütüncü, Y., Küçükler, K., Akbaba, G., Aydın, Y., & Güler, S. (2010) · Endocrine · doi:10.1007/s12020-010-9405-6 · Cited by 39 · see citing works
Kawade, Y., Finter, N. B., & Grossberg, S. E. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(03)00203-5 · Cited by 39 · see citing works
Kordower (1999) · doi:10.1002/1531-8249(199909)46:3
Self-citation
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Filippi, M., Bar-Or, A., Piehl, F., Preziosa, P., Solari, A., Vukusic, S., & Rocca, M. A. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0041-4 · Cited by 1,562 · see citing works
Diagnosis and Treatment of Multiple Sclerosis: A Review
McGinley, M. P., Goldschmidt, C. H., & Rae-Grant, A. D. (2021) · JAMA · doi:10.1001/jama.2020.26858 · Cited by 1,205 · see citing works
Coles, A. J., Twyman, C. L., Arnold, D. L., Cohen, J. A., Confavreux, C., Fox, E. J., Hartung, H.-P., Havrdova, E., Selmaj, K. W., Weiner, H. L., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61768-1 · Cited by 1,198 · see citing works
Self-citationMultiple Sclerosis: Current Knowledge and Future Outlook
Kamm, C. P., Uitdehaag, B. M. J., & Polman, C. H. (2014) · European Neurology · doi:10.1159/000360528 · Cited by 1,011 · see citing works
Treatment of Multiple Sclerosis: A Review
Hauser, S. L., & Cree, B. A. C. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.05.049 · Cited by 969 · see citing works
ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis
Montalbán, X., Gold, R., Thompson, A. J., Otero‐Romero, S., Amato, M. P., Chandraratna, D., Clanet, M., Comı, G., Derfuss, T. J., Fazekas, F., et al. (2018) · Multiple Sclerosis Journal · doi:10.1177/1352458517751049 · Cited by 714 · see citing works
Self-citationTiming of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study
He, A. H., Merkel, B., Brown, J. W. L., Ryerson, L. Z., Kister, I., Malpas, C. B., Sharmin, S., Horáková, D., Havrdová, E., Spelman, T. D., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30067-3 · Cited by 473 · see citing works
Self-citationBrain health: time matters in multiple sclerosis
Giovannoni, G., Butzkueven, H., Dhib-Jalbut, S. S., Hobart, J. C., Kobelt, G., Pepper, G., Sormani, M. P., Thalheim, C., Traboulsee, A. L., & Vollmer, T. L. (2016) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2016.07.003 · Cited by 463 · see citing works
Self-citationMultiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies
Wingerchuk, D. M., & Carter, J. L. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.11.002 · Cited by 416 · see citing works
Harding, K. E., Williams, O., Willis, M., Hrastelj, J., Rimmer, A., Joseph, F., Tomassini, V., Wardle, M., Pickersgill, T. P., Robertson, N. P., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.4905 · Cited by 377 · see citing works
Treatment of multiple sclerosis — success from bench to bedside
Tintoré, M., Vidal‐Jordana, Á., & Sastre‐Garriga, J. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0082-z · Cited by 343 · see citing works
Giovannoni, G., Sørensen, P. S., Cook, S. D., Rammohan, K. W., Rieckmann, P., Comı, G., Dangond, F., Adeniji, A. K., & Vermersch, P. (2017) · Multiple Sclerosis Journal · doi:10.1177/1352458517727603 · Cited by 341 · see citing works
Self-citationMultiple sclerosis—a quiet revolution
Ransohoff, R. M., Hafler, D. A., & Lucchinetti, C. F. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.14 · Cited by 338 · see citing works
Is it time to target no evident disease activity (NEDA) in multiple sclerosis?
Giovannoni, G., Turner, B. P., Gnanapavan, S., Offiah, C. E., Schmierer, K., & Marta, M. (2015) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2015.04.006 · Cited by 338 · see citing works
Self-citationBurt, R. K., Balabanov, R. D., Burman, J., Sharrack, B., Snowden, J. A., Oliveira, M. C., Fagius, J., ROSE, J. W., Nelson, F. M., Barreira, A. A., et al. (2019) · JAMA · doi:10.1001/jama.2018.18743 · Cited by 316 · see citing works
Evolving concepts in the treatment of relapsing multiple sclerosis
Comi, G., Radaelli, M., & Sørensen, P. S. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32388-1 · Cited by 309 · see citing works
Epidemiology and treatment of multiple sclerosis in elderly populations
Vaughn, C. B., Jakimovski, D., Kavak, K. S., Ramanathan, M. K., Benedict, R. H. B., Zivadinov, R., & Weinstock‐Guttman, B. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0183-3 · Cited by 310 · see citing works
Clinical Relevance of Brain Volume Measures in Multiple Sclerosis
Stefano, N. D., Airas, L. M., Grigoriadis, N., Mattle, H. P., O’Riordan, J. I., Oreja‐Guevara, C., Sellebjerg, F. T., Stankoff, B., Walczak, A., Wiendl, H., et al. (2014) · CNS Drugs · doi:10.1007/s40263-014-0140-z · Cited by 302 · see citing works
Sormani, M. P., Arnold, D. L., & Stefano, N. D. (2013) · Annals of Neurology · doi:10.1002/ana.24018 · Cited by 299 · see citing works
Self-citationVaisman‐Mentesh, A., Gutiérrez-González, M., DeKosky, B. J., & Wine, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01951 · Cited by 295 · see citing works
Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis
Baker, D., Marta, M., Pryce, G., Giovannoni, G., & Schmierer, K. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.01.042 · Cited by 290 · see citing works
Self-citationMelzer, N., Ruck, T., Fuhr, P., Gold, R., Hohlfeld, R., Marx, A., Melms, A., Tackenberg, B., Schalke, B. C. G., Schneider‐Gold, C., et al. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8045-z · Cited by 291 · see citing works
Multiple Sclerosis: Immunopathology and Treatment Update
Dargahi, N., Κατσάρα, Μ., Tselios, T. V., Androutsou, M., de Courten, M., Matsoukas, J., & Apostolopoulos, V. (2017) · Brain Sciences · doi:10.3390/brainsci7070078 · Cited by 289 · see citing works
Disease‐modifying treatments for multiple sclerosis – a review of approved medications
Torkildsen, Ø., Myhr, K.-M., & Bø, L. (2015) · European Journal of Neurology · doi:10.1111/ene.12883 · Cited by 283 · see citing works
Cohen, J. A., Comı, G., Selmaj, K. W., Bar‐Or, A., Arnold, D. L., Steinman, L., Hartung, H., Montalbán, X., Havrdová, E., Cree, B., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30238-8 · Cited by 280 · see citing works
Self-citationAlemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings
Coles, A. J., Cohen, J. A., Fox, E. J., Giovannoni, G., Hartung, H.-P., Havrdova, E., Schippling, S., Selmaj, K. W., Traboulsee, A., Compston, D. A. S., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004354 · Cited by 277 · see citing works
Self-citationon behalf of the MAGNIMS study group, Sastre‐Garriga, J., Pareto, D., Battaglini, M., Rocca, M. A., Ciccarelli, O., Enzinger, C., Wuerfel, J. T., Sormani, M. P., Barkhof, F., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0314-x · Cited by 279 · see citing works
B cells in multiple sclerosis — from targeted depletion to immune reconstitution therapies
Cencioni, M. T., Mattoscio, M., Magliozzi, R., Bar‐Or, A., & Muraro, P. A. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00498-5 · Cited by 277 · see citing works
Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?
Gajofatto, A., & Benedetti, M. D. (2015) · World Journal of Clinical Cases · doi:10.12998/wjcc.v3.i7.545 · Cited by 257 · see citing works
Disease-modifying therapies and infectious risks in multiple sclerosis
Winkelmann, A., Loebermann, M., Reisinger, E. C., Hartung, H., & Zettl, U. K. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.21 · Cited by 254 · see citing works
Self-citationSharrack, B., Saccardi, R., Alexander, T., Badoglio, M., Burman, J., Farge, D., Greco, R., Jessop, H., Kazmi, M. A., Киргизов, К. И., et al. (2019) · Bone Marrow Transplantation · doi:10.1038/s41409-019-0684-0 · Cited by 257 · see citing works
Comorbidity in multiple sclerosis: implications for patient care
Marrie, R. A. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.33 · Cited by 250 · see citing works
Overview of Infections in the Immunocompromised Host
Dropulic, L. K., & Lederman, H. M. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.dmih2-0026-2016 · Cited by 249 · see citing works
Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab
Baker, D., Herrod, S. S., Álvarez-González, C., Giovannoni, G., & Schmierer, K. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0676 · Cited by 242 · see citing works
Self-citationAlemtuzumab treatment of multiple sclerosis: long-term safety and efficacy
Tuohy, O., Costelloe, L., Hill-Cawthorne, G., Bjornson, I., Harding, K., Robertson, N., May, K., Button, T., Azzopardi, L., Kousin-Ezewu, O., et al. (2015) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-307721 · Cited by 238 · see citing works
Self-citationHan, Y., Jia, Q., Jahani, P. S., Hurrell, B. P., Pan, C., Huang, P., Gukasyan, J., Woodward, N. C., Eskin, E., Gilliland, F. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15649-3 · Cited by 222 · see citing works
Scolding, N. J., Barnes, D., Cader, S., Chataway, J., Chaudhuri, A., Coles, A. J., Giovannoni, G., Miller, D. H., Rashid, W., Schmierer, K., et al. (2015) · Practical Neurology · doi:10.1136/practneurol-2015-001139 · Cited by 222 · see citing works
Self-citationAlemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy
Havrdova, E., Arnold, D. L., Cohen, J. A., Hartung, H.-P., Fox, E. J., Giovannoni, G., Schippling, S., Selmaj, K. W., Traboulsee, A., Compston, D. A. S., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004313 · Cited by 221 · see citing works
Self-citationECTRIMS / EAN guideline on the pharmacological treatment of people with multiple sclerosis
Montalbán, X., Gold, R., Thompson, A. J., Otero‐Romero, S., Amato, M. P., Chandraratna, D., Clanet, M., Comı, G., Derfuss, T. J., Fazekas, F., et al. (2018) · European Journal of Neurology · doi:10.1111/ene.13536 · Cited by 226 · see citing works
Self-citationNatrajan, M. S., de la Fuente, A. G., Crawford, A. H., Linehan, E., Núñez, V., Johnson, K. R., Wu, T., Fitzgerald, D. C., Ricote, M., Bielekova, B., et al. (2015) · Brain · doi:10.1093/brain/awv289 · Cited by 217 · see citing works
McGuigan, C., Craner, M., Guadagno, J. V., Kapoor, R., Mazibrada, G., Molyneux, P. D., Nicholas, R. S., Palace, J. A., Pearson, O. R., Rog, D. J., et al. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2015-311100 · Cited by 220 · see citing works
Tramacere, I., Giovane, C. D., Salanti, G., D’Amico, R., & Filippini, G. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011381.pub2 · Cited by 215 · see citing works
Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond
Ruck, T., Bittner, S., Wiendl, H., & Meuth, S. G. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160716414 · Cited by 213 · see citing works
Mikulska, M., Lanini, S., Gudiol, C., Drgoňa, Ľ., Ippolito, G., Fernández‐Ruiz, M., & Salzberger, B. (2018) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2018.02.003 · Cited by 213 · see citing works
Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation
Jones, J., Thompson, S. A. J., Loh, P., Davies, J. L., Tuohy, O., Curry, A. J., Azzopardi, L., Hill-Cawthorne, G. A., Fahey, M. T., Compston, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313654110 · Cited by 206 · see citing works
Self-citationBurt, R. K., Balabanov, R. D., Han, X., Sharrack, B., Morgan, A., Quigley, K., Yaung, K., Helenowski, I., Jovanovic, B., Spahovic, D., et al. (2015) · JAMA · doi:10.1001/jama.2014.17986 · Cited by 200 · see citing works
A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis
Marrie, R. A., Reider, N., Cohen, J. A., Stüve, O., Sørensen, P. S., Cutter, G., Reingold, S. C., & Trojano, M. (2014) · Multiple Sclerosis Journal · doi:10.1177/1352458514564490 · Cited by 195 · see citing works
Self-citationOptimizing treatment success in multiple sclerosis
Ziemssen, T., Derfuss, T. J., Stefano, N. D., Giovannoni, G., Palavra, F., Tomic, D., Vollmer, T., & Schippling, S. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7986-y · Cited by 191 · see citing works
Self-citationInfectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies
Davis, J. S., Ferreira, D., Paige, E. K., Gedye, C. A., & Boyle, M. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00035-19 · Cited by 188 · see citing works
Varicella-Zoster Virus Infections in Patients Treated With Fingolimod
Arvin, A. M., Wolinsky, J. S., Kappos, L., Morris, M. I., Reder, A. T., Tornatore, C., Gershon, A. A., Gershon, M. D., Levin, M. J., Bezuidenhoudt, M., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.3065 · Cited by 184 · see citing works
Havrdová, E., Horáková, D., & Kovářová, I. (2015) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285614563522 · Cited by 177 · see citing works
Neurodegeneration in multiple sclerosis
Mey, G. M., Mahajan, K. R., & DeSilva, T. M. (2022) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1583 · Cited by 174 · see citing works
Interferon β for Multiple SclerosisPreprint
Jakimovski, D., Kolb, C., Ramanathan, M. K., Zivadinov, R., & Weinstock‐Guttman, B. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a032003 · Cited by 170 · see citing works
Early highly effective versus escalation treatment approaches in relapsing multiple sclerosis
Ontaneda, D., Tallantyre, E. C., Kalinčík, T., Planchon, S. M., & Evangelou, N. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30151-6 · Cited by 170 · see citing works
High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS
Nash, R. A., Hutton, G. J., Racke, M. K., Popat, U., Devine, S. M., Steinmiller, K. C., Griffith, L. M., Muraro, P. A., Openshaw, H., Sayre, P. H., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003660 · Cited by 167 · see citing works
Self-citationDisease modifying therapies for relapsing multiple sclerosis
Wingerchuk, D. M., & Weinshenker, B. G. (2016) · BMJ · doi:10.1136/bmj.i3518 · Cited by 167 · see citing works
Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm
Giovannoni, G. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000561 · Cited by 165 · see citing works
Self-citationUpdates and Advances in Multiple Sclerosis Neurotherapeutics
Amin, M., & Hersh, C. M. (2022) · Neurodegenerative Disease Management · doi:10.2217/nmt-2021-0058 · Cited by 171 · see citing works
Kalinčík, T., Brown, J. W. L., Robertson, N. P., Willis, M., Scolding, N. J., Rice, C. M., Wilkins, A., Pearson, O. R., Ziemssen, T., Hutchinson, M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30007-8 · Cited by 164 · see citing works
Self-citationZhang, X., Tao, Y., Chopra, M., Ahn, M., Marcus, K. L., Choudhary, N. R., Hongtu Zhu, B., & Markovic‐Plese, S. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301926 · Cited by 162 · see citing works
Initial high-efficacy disease-modifying therapy in multiple sclerosis
Buron, M. D., Chalmer, T. A., Sellebjerg, F. T., Barzinji, I., Sindberg, D. B., Christensen, J. R., Christensen, M. K., Hansen, V., Illés, Z., Jensen, H. B., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000010135 · Cited by 163 · see citing works
Promoting remyelination in multiple sclerosis
Cunniffe, N. G., & Coles, A. J. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09421-x · Cited by 161 · see citing works
Self-citationBrain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options
Andravizou, A., Dardiotis, E., Artemiadis, A., Sokratous, M., Siokas, V., Tsouris, Z., Aloizou, A., Nikolaidis, I., Bakirtzis, C., Tsivgoulis, G. K., et al. (2019) · Autoimmunity Highlights · doi:10.1186/s13317-019-0117-5 · Cited by 153 · see citing works
Immunological Aspects of Approved MS Therapeutics
Rommer, P. S., Milo, R., Han, M. H., Satyanarayan, S., Sellner, J., Hauer, L., Illés, Z., Warnke, C., Laurent, S. A., Weber, M. S., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01564 · Cited by 157 · see citing works
Rae-Grant, A. D., Day, G. S., Marrie, R. A., Rabinstein, A. A., Cree, B., Gronseth, G., Haboubi, M., Halper, J., Hosey, J. P., Jones, D., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000005345 · Cited by 153 · see citing works
Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells
Ceronie, B., Jacobs, B. M., Baker, D., Dubuisson, N., Mao, Z., Ammoscato, F., Lock, H., Longhurst, H. J., Giovannoni, G., & Schmierer, K. (2018) · Journal of Neurology · doi:10.1007/s00415-018-8830-y · Cited by 148 · see citing works
Self-citationGholamzad, M., Ebtekar, M., Ardestani, M. S., Azimi, M., Mahmodi, Z., Mousavi, M. J., & Aslani, S. (2018) · Inflammation Research · doi:10.1007/s00011-018-1185-0 · Cited by 147 · see citing works
Assessing treatment outcomes in multiple sclerosis trials and in the clinical setting
Tur, C., Moccia, M., Barkhof, F., Chataway, J., Sastre‐Garriga, J., Thompson, A. J., & Ciccarelli, O. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.171 · Cited by 146 · see citing works
Epstein, D. J., Dunn, J., & Deresinski, S. C. (2018) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofy174 · Cited by 146 · see citing works
The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis
Mallucci, G., Peruzzotti‐Jametti, L., Bernstock, J. D., & Pluchino, S. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.02.003 · Cited by 143 · see citing works
High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis
Freeman, L. A., Longbrake, E. E., Coyle, P. K., Hendin, B. A., & Vollmer, T. R. (2022) · CNS Drugs · doi:10.1007/s40263-022-00965-7 · Cited by 147 · see citing works
Established and novel disease‐modifying treatments in multiple sclerosis
Cross, A. H., & Naismith, R. T. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12203 · Cited by 142 · see citing works
Both cladribine and alemtuzumab may effect MS via B-cell depletion
Baker, D., Herrod, S. S., Álvarez-González, C., Zalewski, L., Albor, C., & Schmierer, K. (2017) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000360 · Cited by 140 · see citing works
Update on Disease-Modifying Therapies for Multiple Sclerosis
Vargas, D. L., & Tyor, W. R. (2017) · Journal of Investigative Medicine · doi:10.1136/jim-2016-000339 · Cited by 138 · see citing works
Therapeutic Advances in Multiple Sclerosis
Yang, J. H., Rempe, T., Whitmire, N., Dunn‐Pirio, A., & Graves, J. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.824926 · Cited by 142 · see citing works
Svenningsson, A., Frisell, T., Burman, J., Salzer, J., Fink, K., Hallberg, S., Hambraeus, J., Axelsson, M., Nimer, F. A., Sundström, P., et al. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00209-5 · Cited by 141 · see citing works
No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine
Pakpoor, J., Disanto, G., Altmann, D. R., Pavitt, S. H., Turner, B. P., Marta, M., Juliusson, G., Baker, D., Chataway, J., & Schmierer, K. (2015) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000158 · Cited by 134 · see citing works
Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: A systematic review
Merkel, B., Butzkueven, H., Traboulsee, A. L., Havrdová, E., & Kalinčík, T. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.04.010 · Cited by 134 · see citing works
Early Aggressive Treatment Approaches for Multiple Sclerosis
Simpson, A. C., Mowry, E. M., & Newsome, S. D. (2021) · Current Treatment Options in Neurology · doi:10.1007/s11940-021-00677-1 · Cited by 134 · see citing works
Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations
Freedman, M. S., Devonshire, V. A., Duquette, P., Giacomini, P. S., Giuliani, F., Levin, M. C., Montalbán, X., Morrow, S. A., Oh, J., Rotstein, D., et al. (2020) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2020.66 · Cited by 132 · see citing works
Kalincik, T., Spelman, T., Trojano, M., Duquette, P., Izquierdo, G., Grammond, P., Lugaresi, A., Hupperts, R., Cristiano, E., van Pesch, V., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063480 · Cited by 128 · see citing works
Aggressive multiple sclerosis: proposed definition and treatment algorithm
Rush, C., MacLean, H. J., & Freedman, M. S. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.85 · Cited by 128 · see citing works
Dulamea, A. O. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-47861-6_7 · Cited by 128 · see citing works
New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis
English, C., & Aloi, J. J. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.03.001 · Cited by 126 · see citing works
GM-CSF in Neuroinflammation: Licensing Myeloid Cells for Tissue Damage
Croxford, A. L., Spath, S., & Becher, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.004 · Cited by 125 · see citing works
Current and emerging disease‐modulatory therapies and treatment targets for multiple sclerosis
Piehl, F. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13215 · Cited by 125 · see citing works
The immunological function of CD52 and its targeting in organ transplantation
Zhao, Y., Su, H., Shen, X., Du, J., Zhang, X., & Zhao, Y. X. (2017) · Inflammation Research · doi:10.1007/s00011-017-1032-8 · Cited by 120 · see citing works
Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS
Akgün, K., Kretschmann, N., Haase, R., Proschmann, U., Kitzler, H. H., Reichmann, H., & Ziemssen, T. (2019) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000555 · Cited by 124 · see citing works
Fogarty, E., Schmitz, S., Tubridy, N. J., Walsh, C., & Barry, M. G. (2016) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2016.06.001 · Cited by 119 · see citing works
Pardo, G., & Jones, D. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8594-9 · Cited by 119 · see citing works
Thinking outside the box: non-canonical targets in multiple sclerosis
Bierhansl, L., Hartung, H., Aktaş, O., Ruck, T., Roden, M., & Meuth, S. G. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00477-5 · Cited by 119 · see citing works
Self-citationEfficacy classification of modern therapies in multiple sclerosis
Samjoo, I. A., Worthington, E., Drudge, C., Zhao, M., Cameron, C. G., Häring, D. A., Stoneman, D., Klotz, L., & Adlard, N. (2021) · Journal of Comparative Effectiveness Research · doi:10.2217/cer-2020-0267 · Cited by 117 · see citing works
Axisa, P., & Hafler, D. A. (2016) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000319 · Cited by 118 · see citing works
Guidelines on the use of irradiated blood components
Foukaneli, T., Kerr, P., Bolton‐Maggs, P. H. B., Cardigan, R. A., Coles, A. J., Gennery, A. R., Jane, D., Kumararatne, D. S., Manson, A. L., New, H. V., et al. (2020) · British Journal of Haematology · doi:10.1111/bjh.17015 · Cited by 113 · see citing works
Self-citationDefining and scoring response to IFN-β in multiple sclerosis
Sormani, M. P., & Stefano, N. D. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.146 · Cited by 111 · see citing works
Therapies for multiple sclerosis: translational achievements and outstanding needs
Haghikia, A., Hohlfeld, R., Gold, R., & Fugger, L. H. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.03.004 · Cited by 105 · see citing works
Risk of relapse phenotype recurrence in multiple sclerosis
Kalinčík, T., Buzzard, K. A., Jokubaitis, V., Trojano, M., Duquette, P., Izquierdo, G., Girard, M., Lugaresi, A., Grammond, P., Grand’Maison, F., et al. (2014) · Multiple Sclerosis Journal · doi:10.1177/1352458514528762 · Cited by 108 · see citing works
New management algorithms in multiple sclerosis
Sørensen, P. S. (2014) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000096 · Cited by 106 · see citing works
Rae-Grant, A. (2019) · Neurology · doi:10.1212/wnl.0000000000008376 · Cited by 103 · see citing works
Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort
Willis, M., Harding, K. E., Pickersgill, T. P., Wardle, M., Pearson, O. R., Scolding, N. J., Smee, J., & Robertson, N. (2015) · Multiple Sclerosis Journal · doi:10.1177/1352458515614092 · Cited by 101 · see citing works
- Authors
- Cohen, J. A., Coles, A. J., Arnold, D. L., Confavreux, C., Fox, E. J., Hartung, H.-P., Havrdova, E., Selmaj, K. W., Weiner, H. L., Fisher, E., Brinar, V. V., Giovannoni, G., Stojanovic, M., Ertik, B. I., Lake, S. L., Margolin, D. H., Panzara, M. A., & Compston, D. A. S.
- Affiliations
- Cleveland Clinic (US)
- University of Cambridge (GB)
- Montreal Neurological Institute and Hospital (CA)
- Lyon 1 Université (FR)
- Central Texas Neurology Consultants (US)
- Heinrich Heine University Düsseldorf (DE)
- Medical University of Lodz (PL)
- Brigham and Women's Hospital (US)
- University Hospital Centre Zagreb (HR)
- Queen Mary University of London (GB)
- Clinical Centre of Kragujevac (RS)
- Corresponding author
- Cohen, Jeffrey A
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 380
- Issue
- 9856
- Pages
- 1819-1828
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2148766438
- Cited by
- 1,205
- References
- 39
- Citations by year
- 2026: 25 · 2025: 52 · 2024: 66 · 2023: 71 · 2022: 70 · 2021: 77 · 2020: 109 · 2019: 112 · 2018: 108 · 2017: 120 · 2016: 112 · 2015: 104 · 2014: 85 · 2013: 83 · 2012: 6
- FWCI
- 64.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0508-10335)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Keywords
- alemtuzumab, interferon beta-1a, relapsing-remitting multiple sclerosis, first-line therapy, anti-CD52 monoclonal antibody, relapse rate, disability progression, disease-modifying therapy, treatment safety, treatment-naive patients, relapse-free survival, time to treatment discontinuation, adverse events, immunosuppression
- MeSH terms
- Interferon beta-1a, Alemtuzumab, Adjuvants, Immunologic, Administration, Cutaneous, Adolescent, Adult, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Recurrence, Treatment Outcome, Interferon-beta, Disease-Free Survival, Multiple Sclerosis, Relapsing-Remitting, Kaplan-Meier Estimate, Young Adult, Antibodies, Monoclonal, Humanized
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