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Multicenter Study
. 2024 Jun;31(6):e16250.
doi: 10.1111/ene.16250. Epub 2024 Mar 28.

Therapeutic choices and disease activity after 2 years of treatment with cladribine: An Italian multicenter study (CladStop)

Irene Schiavetti  1 , Alessio Signori  1 , Angela Albanese  1 , Jessica Frau  2 , Eleonora Cocco  2   3 , Lorena Lorefice  2 , Sonia di Lemme  4 , Roberta Fantozzi  4 , Diego Centonze  4   5 , Doriana Landi  6 , Girolama Marfia  6 , Elisabetta Signoriello  7 , Giacomo Lus  7 , Chiara Zecca  8   9 , Claudio Gobbi  8   9 , Rosa Iodice  10 , Leonardo Malimpensa  11 , Cinzia Cordioli  12 , Diana Ferraro  13 , Francesca Ruscica  14 , Livia Pasquali  15 , Anna Repice  16 , Paolo Immovilli  17 , Maria Teresa Ferrò  18 , Simona Bonavita  19 , Massimiliano Di Filippo  20 , Gianmarco Abbadessa  21 , Flora Govone  22 , Maria Pia Sormani  1   23 ; CladStop study group
Collaborators, Affiliations
Multicenter Study

Therapeutic choices and disease activity after 2 years of treatment with cladribine: An Italian multicenter study (CladStop)

Irene Schiavetti et al. Eur J Neurol. 2024 Jun.

Abstract

Background and purpose: Cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited.

Methods: This retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2-year course of cladribine treatment. The primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2-year treatment course.

Results: A total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. The study found a significant reduction in annualized relapse rate at the 12-month follow-up after cladribine completion compared to the year prior to starting therapy (0.07 ± 0.25 vs. 0.82 ± 0.80, p < 0.001). Furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. The safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event.

Conclusions: This study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. Real-world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. However, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long-term impact are necessary.

Keywords: cladribine; efficacy; multiple sclerosis; real‐world data; safety; treatment response.

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Conflict of interest statement

Abbadessa Gianmarco personal compensation from Janssen and Merck for traveling and/or advisory boards. Albanese Angela is an employee of Merck Serono S.p.A., Rome, Italy, an affiliate of Merck KGaA, Darmstadt, Germany. Bonavita Simona was Speaker and/or AB honoraria from Novartis, BMS, Merck Serono, Biogen, Janssen Cilag, Alezio, Horizon, Roche. Centonze Diego is an advisory board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi‐Genzyme and Teva and has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi‐Genzyme and Teva. He also is the principal investigator in clinical trials for Bayer Schering, Biogen, Merck KGaA (Darmstadt, Germany), Mitsubishi, Novartis, Roche, Sanofi‐Genzyme and Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi‐Genzyme and Teva. Cocco Eleonora serves on scientific advisory boards and received honoraria for speaking from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Roche, and Sanofi Genzyme. Cordioli Cinzia received Honoraria for travelling or speaking in advisory Board from Biogen, Novartis, Merck Serono, Roche, BMS. Di Filippo Massimiliano participated on advisory boards and steering committees for and received speaker or writing honoraria, research support and funding fortravelling from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva and Viatris. Fantozzi Roberta received honoraria or consultation fees from Roche, Novartis, Merck Serono, BMS. Ferraro Diana has received travel grants and/or fees for speaking and/or advisory boards from Alexion, Biogen, Bristol‐Myers Squibb, Celgene, Merck, Novartis, Roche, Sanofi. Frau Jessica serves on scientific advisory boards for Biogen, Merck, Genzyme, Novartis, and has received honoraria as a speaker from Merck, Biogen, Novartis, Genzyme, TEVA, Alexion. Gobbi Claudio received consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche. (Ente Ospedaliero Cantonale (employer) received compensation for Gobbi Claudio's speaking activities). Govone Flora received grants from Roche. Immovilli Paolo received fees for speaking or advising from Roche, Biogen, Sanofi, Bristol Squibb Meyers, Novartis and Merck. Iodice Rosa reports personal fees from Merck, Biogen, Teva, Sanofi Genzyme, Roche, Almirall, Viatris. Landi Doriana received travel funding from Biogen, Merck‐Serono, Sanofi‐Genzyme, Teva, speaking or consultations fees from Sanofi‐Genzyme, Merck‐Serono, Teva, Biogen, Roche; Research sponsorship from Roche. Lorefice Lorena received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi, Genzyme, Serono and Teva and Almirall. Lus Giacomo received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Sanofi‐Aventis Pharmaceuticals, Teva neuroscience as a consultant and speaker and received research support from Biogen Idec, Merck Serono, and Novartis. Marfia Girolama Alessandra received speaking or consultation fees from Almirall, Bayer‐Schering, Biogen, Genzyme, Merck‐Serono, Novartis, Teva, Sanofi‐Genzyme. Pasquali Livia received personal compensations for speaking or consultancy from Sanofi, Novartis, Merck, Alexion, Biogen; and supporting for attending meetings from Sanofi, Merck. Repice Anna Maria has received honoraria for speaking and for participating to advisory board from Merck, Biogen‐Idec, Sanofi‐Genzyme, Novartis, Roche, Bristol Mayer. Schiavetti Irene received consulting fees from Horizon, Hippocrates Research, Eyepharma, Hoya Holding N.V., DMG Italia and DreamsLab. Signori Alessio received consulting fees from Horizon, Chiesi and Sanofi‐Genzyme outside of this work. Signoriello Elisabetta received personal compensation from Almirall, Biogen, Genzyme, Novartis, and Teva fortraveling and advisory boards. Sormani MP received consulting fees from Roche, Biogen, Merck, Novartis, Sanofi, Celgene, Immunic, Geneuro, GSK, Medday; received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Roche, Biogen Merck, Novartis, Sanofi, Celgene; participated on a Data Safety Monitoring Board or Advisory Board for Roche, Sanofi, Novartis, Merck. Zecca Chiara received consulting fees, or research grants from Almirall, Biogen Idec, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sanofi, Teva Pharma, Roche [Ente Ospedaliero Cantonale (employer) received compensation for Zecca Chiara's speaking activities]. Other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Therapeutic choice after CladStop. DMT, disease‐modifying therapy.
FIGURE 2
FIGURE 2
Annualized relapse rate before, during, and after cladribine. * indicates statistically significant.
FIGURE 3
FIGURE 3
Lymphocyte count during 2 years of treatment.
See this image and copyright information in PMC

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