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. 2022 Jan;29(1):257-266.
doi: 10.1111/ene.15121. Epub 2021 Oct 5.

A real-world study of alemtuzumab in a cohort of Italian patients

Cinzia Valeria Russo  1 , Francesco Saccà  1 , Jessica Frau  2 , Pietro Annovazzi  3 , Elisabetta Signoriello  4 , Simona Bonavita  4 , Roberta Grasso  5 , Marinella Clerico  6 , Cinzia Cordioli  7 , Alice Laroni  8 , Marco Capobianco  9 , Valentina Torri Clerici  10 , Arianna Sartori  11 , Paola Cavalla  12 , Giorgia Teresa Maniscalco  13 , Sara La Gioia  14 , Francesca Caleri  15 , Alessia Giugno  16 , Rosa Iodice  1 , Antonio Carotenuto  1 , Eleonora Cocco  2 , Giuseppe Fenu  2 , Mauro Zaffaroni  3 , Damiano Baroncini  3 , Giacomo Lus  4 , Antonio Gallo  17 , Stefania Federica De Mercanti  6 , Caterina Lapucci  8 , Valeria Di Francescantonio  5 , Laura Brambilla  10 , Maria Pia Sormani  18 , Alessio Signori  18
Affiliations

A real-world study of alemtuzumab in a cohort of Italian patients

Cinzia Valeria Russo et al. Eur J Neurol. 2022 Jan.

Abstract

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab.

Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation.

Results: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow-up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous-year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression-free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re-baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years.

Conclusions: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.

Keywords: alemtuzumab; cohort; efficacy; real-world evidence; safety.

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Conflict of interest statement

Francesco Saccà has received honoraria for public speaking and/or for advisory boards from Alexion, Almirall, Argenx, Avexis, Biogen, Forward Pharma, Lexeo, Merck, Mylan, Novartis, Pomona, Sanofi, Roche, Takeda and Teva. Cinzia Valeria Russo has nothing to disclose. Roberta Grasso has received honoraria for public speaking and/or for advisory boards from Merck, Biogen, Sanofi and Novartis. Jessica Frau serves on scientific advisory boards for Biogen and Genzyme, and has received honoraria as a speaker from Merck Serono, Genzyme, Biogen and Teva. Pietro Annovazzi has received personal compensation for speaking at meetings or participating in advisory boards from Almirall, Biogen, Merck, Mylan, Novartis, Roche, Sanofi and TEVA. Elisabetta Signoriello has received personal compensation from Almirall, Biogen, Genzyme, Novartis and Teva for traveling and advisory boards. Simona Bonavita has received honoraria for public speaking and/or for advisory boards from Roche, Novartis, Teva, Genzyme, Merck Serono and Biogen. Roberta Grasso has received compensation for serving on advisory boards for Merck, Biogen, Sanofi and Novartis. Marinella Clerico has received personal compensation as an invited speaker to conferences or for participating on advisory committee or boards from Merck, Biogen, Novartis, Sanofi‐ Genzyme and Pomona, and has received sponsorship to attend congresses from Merck, Biogen, Novartis, Sanofi‐Genzyme and Almirall. Cinzia Cordioli has received personal compensation for speaking and travel grants from Biogen, Novartis, TEVA, Merck Serono and Almirall. Alice Laroni has received financial support for travel and attending meetings from Merck, Sanofi Genzyme, Teva, Biogen and Novartis. Marco Capobianco has received personal compensation for speaking at meetings or participating on advisory boards from Almirall, Biogen, Merck, Novartis, Roche, Sanofi and TEVA. Valentina Torri Clerici acted as an Advisory Board member of Teva, Merck, Roche, Biogen, Novartis and Almirall, has received funding for traveling by Genzyme, Merck and Roche, and has received honoraria for speaking or writing from Genzyme, Novartis and Almirall. She received support for research projects from Almirall. Arianna Sartori has received funding for travel and/or speaker honoraria from Novartis, Teva, Merk, Genzyme, Roche and Biogen. Paola Cavalla received support for participation in scientific meetings or personal compensation for speaking at meetings or on advisory boards from Almirall, Biogen, Merck, Novartis, Roche, Sanofi and TEVA. Giorgia Teresa Maniscalco received personal compensation from Novartis, Genzyme, Biogen, Merck Serono, and TEVA for public speaking and advisory boards. Sara La Gioia has nothing to disclose. Francesca Caleri has received honoraria for advisory boards and/or for public speaking, and/or travel grants from Biogen, Merck, Teva, Sanofi‐Genzyme and Roche. Alessia Giugno has received sponsorship for travel and attending meeting from Sanofi‐Genzyme. Rosa Iodice has received honoraria for advisory boards and/or travel grants and/or public speaking fees from Biogen, Merck, Mylan, Sanofi and Roche. Antonio Carotenuto has received research grants from ALMIRALL and ECTRIMS‐MAGNIMS society, and honoraria form Novartis, Merck and Biogen. Eleonora Cocco has received research grants and honoraria as a speaker and member of advisory boards from Almirall, Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, Teva and Roche. Giuseppe Fenu has received honoraria for consultancy from Novartis and Biogen and for speaking from Merck and Teva. Mauro Zaffaroni has received financial support for attending scientific meetings from Biogen, Genzyme, Merck Serono, Novartis, Sanofi‐Aventis and Teva, and received funds for his department from Novartis. Damiano Baroncini has received honoraria from Almirall for the creation of editorial publications, and travel grants for participation to international congresses from Genzyme and TEVA. Giacomo Lus has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis and Sanofi‐Aventis Pharmaceuticals, and with Teva Neuroscience as a consultant and speaker, and has received research support from Biogen Idec, Merck Serono and Novartis. Antonio Gallo A.G. received honoraria for speaking and travel grants from Biogen, Sanofi‐Aventis, Merck, Genzyme, Teva and Novartis. Stefania De Mercanti has received sponsorship to attend congresses from Merck, Biogen, Novartis, Sanofi‐Genzyme and Almirall. Caterina Lapucci has nothing to disclose. Valeria Di Francescantonio has nothing to disclose. Maria Pia Sormani has received consulting fees from Biogen, Merck, Teva, Genzyme, Roche, Novartis, GeNeuro and Medday. Laura Brambilla has received honoraria for speaking from Novartis and for traveling from Sanofi‐Genzyme and Roche, and has acted as an Advisory Board member of Sanofi‐Genzyme and is involved as principal investigator in clinical trials for Roche and Merck‐Serono. Alessio Signori has received teaching honoraria from Novartis outside this work.

Figures

FIGURE 1
FIGURE 1
Frequency distribution of pre‐alemtuzumab disease‐modifying therapies (DMTs)
FIGURE 2
FIGURE 2
Annualized relapse (ARR) in the overall population (a), in patients switching form natalizumab (b) and from the second year for patients showing relapses between the first and second course of alemtuzumab (c)
FIGURE 3
FIGURE 3
Temporal distribution of relapses during pre‐alemtuzumab washout
FIGURE 4
FIGURE 4
Impact of alemtuzumab on disability progression and improvement
FIGURE 5
FIGURE 5
Impact of alemtuzumab on disease activity. MRI, magnetic resonance imaging
See this image and copyright information in PMC

References

    1. Cox AL, Thompson SA, Jones JL, et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005;35(11):3332‐3342. - PubMed
    1. Hu Y, Turner MJ, Shields J, et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology. 2009;128(2):260‐270. - PMC - PubMed
    1. Gilmore W, Lund BT, Li P, et al. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing‐remitting multiple sclerosis. J Neuroinflammation. 2020;17(1):189. 10.1186/s12974-020-01847-9 - DOI - PMC - PubMed
    1. Rolla S, Maglione A, De Mercanti SF, Clerico M. The meaning of immune reconstitution after alemtuzumab therapy in multiple sclerosis. Cells. 2020;9:1396. - PMC - PubMed
    1. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first‐line treatment for patients with relapsing‐remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819‐1828. - PubMed

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