No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study

Prosperini, Luca; Annovazzi, Pietro; Boffa, Laura; Buscarinu, Maria Chiara; Gallo, Antonio; Matta, Manuela; Moiola, Lucia; Musu, Luigina; Perini, Paola; Avolio, Carlo; Barcella, Valeria; Bianco, Assunta; Farina, D.; Ferraro, Elisabetta; Pontecorvo, Simona; Granella, Franco; Grimaldi, Luigi M. E.; Laroni, Alice; Lus, Giacomo; Patti, Francesco; Pucci, Eugenio; Pasca, Matteo; Sarchielli, Paola; Ghezzi, Angelo; Zaffaroni, Mauro; Baroncini, Damiano; Buttari, Fabio; Centonze, Diego; Fornasiero, Arianna; Salvetti, Marco; Docimo, Renato; Signoriello, Elisabetta; Tedeschi, Gioacchino; Bertolotto, Antonio; Capobianco, Marco; Comı, Gıancarlo; Cocco, Eleonora; Gallo, Paolo; Puthenparampil, Marco; Grasso, Roberta; Francescantonio, Valeria Di; M, Rottoli; Mirabella, Massimiliano; Lugaresi, Alessandra; Luca, Giovanna De; Ioia, Maria di; Tommaso, V. Di; Mancinelli, Luca; Battista, Giancarlo Di; Francia, Ada; Ruggieri, Serena; Pozzilli, Carlo; Curti, Erica; Tsantes, Elena; Palmeri, Barbara; Lapicci, Caterina; Mancardi, Giovanni Luigi; Uccelli, Antonio; Chisari, Clara Grazia; D’Amico, Emanuele; Cartechini, Elisabetta; Repice, Anna Maria; Magnani, Eliana; Massaccesi, Luca; Calabresi, Paolo; Filippo, Massimiliano Di; Gregorio, Maria Di

doi:10.1007/s00415-018-9070-x

Cited by 48 publications

(50 citation statements)

References 32 publications

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“…In the field of multiple sclerosis (MS), there is a growing interest in the use of real-world data to evaluate outcomes of drug treatments [6][7][8][9][10][11]. Some disease-modifying therapies (DMTs) for MS have proven their efficacy in randomized clinical trial (RCT) but were not always equally effective for patients in real-world clinical practice [6,7].…”

Section: Introductionmentioning

confidence: 99%

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis

Daniels¹,

Nat²,

Frequin

et al. 2020

Multiple Sclerosis International

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Background. Recently, ocrelizumab (Ocrevus®) was approved for the treatment of primary progressive multiple sclerosis (PPMS) based on data from the ORATORIO clinical trial. Real-world data about the clinical effectiveness of ocrelizumab has yet to be gathered. Objective. The aim of this study was to provide data about the clinical effectiveness of ocrelizumab for patients diagnosed with PPMS in a real-world setting. Methods. We conducted a retrospective cohort study of all patients with PPMS who started ocrelizumab treatment (n=21) in St. Antonius Hospital (Utrecht/Nieuwegein, the Netherlands) between April 2018 and December 31, 2018. Primary outcome was pre- versus post-ocrelizumab disability worsening rate (from 96 weeks prior to first ocrelizumab administration up to 24 weeks post first ocrelizumab administration). Results. Disability worsening rate while on treatment significantly differed (lower) from disability worsening rate in pre-treatment period (Z=−2.81, p≤.01). Three out of 17 patients showed a clinically relevant improvement in disability status after treatment start. Conclusion. Ocrelizumab can stabilize disability progression in patients with PPMS. Some patients even showed a clinically relevant improvement in disability status. Further research should help to identify which patients benefit most from ocrelizumab.

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Section: Introductionmentioning

confidence: 99%

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis

Daniels¹,

Nat²,

Frequin

et al. 2020

Multiple Sclerosis International

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“…Alemtuzumab is an anti-CD52 monoclonal antibody that depletes and repopulates circulating T and B lymphocytes, thereby shifting cytokine expression toward a less-inflammatory condition 1. Alemtuzumab was shown to be a highly efficacious therapy with tolerable safety in previous studies—including clinical trials—that mainly involved Western patients with multiple sclerosis (MS) 234567891011. The prevalence of MS is much higher in Western populations than in Asian populations, and various disease-modifying therapies (DMTs) for MS have been approved later in Asian countries than in Western countries 1213.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Outcome of Alemtuzumab in Korean Patients with Multiple Sclerosis: 2-Year Follow-Up

et al. 2019

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Background and Purpose Alemtuzumab has shown high efficacy in clinical trials that primarily involved Western multiple sclerosis (MS) patients. To evaluate the therapeutic outcome of alemtuzumab in Korean patients with MS. Methods This study enrolled 23 consecutive patients who were treated with alemtuzumab from 2015 to 2018. Efficacy was evaluated using the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), and radiological activity. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of the EDSS score, and no radiological activity. The safety profiles were also assessed. Results The mean age was 36 years and 16 of the patients were female. Seventeen and 12 of 23 patients were followed up for 1 year and 2 years, respectively. The ARR was markedly reduced from 1.52 during the 1-year period preceding alemtuzumab administration to 0.21 after initiating alemtuzumab ( p <0.001). During the first and second years after initiating alemtuzumab, EDSS worsening was observed in 3 (18%) and 0 (0%) patients, respectively, and radiological activity was exhibited in 9 (53%) and 4 (33%). NEDA was observed in 6 (35%) patients during the first year and in 8 (67%) patients during the second year. Intriguingly, one patient experienced 2 severe clinical exacerbations, which occurred at 10 months after the first and 10 months after the second infusion of alemtuzumab. Nineteen of the 23 patients exhibited infusion-associated reactions and 3 patients exhibited herpes zoster infection. Thyroid dysfunction occurred in two patients at 18 and 20 months after initiating alemtuzumab. Conclusions Consistent with observations in Western populations, alemtuzumab therapy in Korean MS patients led to marked reductions of disease activity without unexpected safety issues.

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“…Improvement was defined as a decrease in EDSS score from baseline of at least 1 point for baseline EDSS < 5.5 or of at least 0.5 points for baseline EDSS ⩾ 5.5, confirmed at 6 months or more. 2,3 The first visit when the improvement is reached was defined as the time to improvement start. The time to improvement stop was defined as the time between baseline and the time when EDSS returned to a value equal to or higher than the baseline value (or to a value not qualifying for the improvement definition), confirmed for 6 months or more.…”

Section: Improvement Definitionmentioning

confidence: 99%

Prevalence of disability improvement as a potential outcome for multiple sclerosis trials

et al. 2020

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Background: The concept of improvement of disability recently emerged as a new target in multiple sclerosis (MS) studies since the approval of new potent drugs and for testing drugs for neuroprotection and repair. Objective: To propose a simple estimator for assessing and comparing the prevalence of improvement over time between groups. Methods: The prevalence of a transient condition takes into account the incidence and the duration of such condition. We propose here the application of a modified Kaplan–Meier estimator to evaluate and compare between groups the prevalence of improvement over time in a cohort of 121 patients treated with autologous hematopoietic stem cell transplantation. Results: The prevalence of improvement after 5 years from transplant was 50.3% (95%CI: [38.0–63.0]) in relapsing–remitting patients and 6.5% (95%CI: [0–17.8]) in secondary-progressive patients ( p < 0.001). Such a difference wouldn’t be evident considering the traditional cumulative probability of improvement at 5 years (55.5% in relapsing–remitting vs 33.4% in secondary-progressive patients, p = 0.10). Conclusion: This study shows the relevance of a new estimator of prevalence of improvement in MS. This estimator gives simple information on whether a drug can induce a durable improvement in disability and can be considered a potential outcome for trials assessing drugs for neuroprotection or repair.

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No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study

Cited by 48 publications

References 32 publications

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis

Real-World Results of Ocrelizumab Treatment for Primary Progressive Multiple Sclerosis

Therapeutic Outcome of Alemtuzumab in Korean Patients with Multiple Sclerosis: 2-Year Follow-Up

Prevalence of disability improvement as a potential outcome for multiple sclerosis trials

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