Three years of experience: the Italian registry and safety data update

Mancardi, Gianluigi; Tedeschi, Gioacchino; Amato, Maria Pia; D’Alessandro, Roberto; Drago, Filippo; Milanese, C.; Popoli, Patrizia; Rossi, Pasqualino; Savettieri, Giovanni; Tola, Maria Rosaria; Comı, Gıancarlo; Pozzilli, Carlo; Bertolotto, Antonio; Marrosu, Maria Giovanna; Grimaldi, Luigi Maria Edoardo; Laroni, Alice; Vanacore, Nicola; Covezzoli, Anna; Rosa, Marisa De; Piccinni, Carlo; Motola, Domenico; Periotto, Laura; Iommelli, R.; Tomino, Carlo; Provinciali, Leandro

doi:10.1007/s10072-010-0356-8

Cited by 28 publications

(27 citation statements)

References 3 publications

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“…The proportion of patients who discontinued treatment was higher in our cohort than in other observational studies, but in the other studies not all patients had reached 2 full years of treatment, thus inducing an underestimation of discontinuation [4][5][6][7][8][9]. The reasons for discontinuing natalizumab were numerous in our study, as in other studies, but the classification and distribution could be relatively different, thus making any comparison difficult.…”

Section: Discussioncontrasting

confidence: 61%

“…We observed a better radiological response and a worse clinical response than that reported in the AFFIRM cohort. As in all observational post-marketing studies [4][5][6][7][8][9], our population of patients treated with natalizumab had a higher disease duration, baseline EDSS, ARR and more often previously been treated by immunomodulatory drugs than in AFFIRM study [1]. Nevertheless, our cohort had a shorter disease duration, higher baseline EDSS and similar ARR compared to other post-marketing studies.…”

Section: Discussioncontrasting

confidence: 34%

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Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

et al. 2011

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"Disease activity free" in relapsing-remitting multiple sclerosis (RRMS) is a new concept introduced by the results of the AFFIRM study. Our objective was to analyze the clinical and radiological efficacy of natalizumab treatment in actual clinical practice and compare it with the post hoc analysis of the AFFIRM study. All patients with RRMS who began treatment with natalizumab at our two French MS centres between April 2007 and May 2008 were included and followed-up for at least 2 years. No measurable disease activity ("disease activity free") was defined as no activity on clinical measures (no relapses and no sustained disability progression) and radiological measures (no gadolinium-enhancing lesions and no new T2-hyperintense lesions on cerebral MRI). A total of 193 patients were included. Natalizumab was discontinued in 25.9% of cases before the completion of 2 years of treatment. In our cohort, we observed patients with more severe disease than in the AFFIRM study. The proportion of patients remaining free of clinical activity during 2 years of treatment was lower than in the AFFIRM study (37.8% vs. 64.3%). The proportion of patients remaining free of radiological activity during 2 years of treatment was higher than in the AFFIRM study (68.9% vs. 57.7%), while the proportion of patients remaining free of disease activity during 2 years of treatment was comparable to the AFFIRM study (33.3% vs. 36.7%). Natalizumab seems to be as effective in a real-life setting as in pivotal and post hoc studies. The confirmation of such benefits is important because of the progressive multifocal leukoencephalopathy risk.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussioncontrasting

confidence: 34%

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

et al. 2011

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“…Most published studies on this topic are descriptive [5,7,10-16]. Few research papers have attempted to correlate baseline data with outcome towards prediction of treatment response, and results are not always consistent between studies, possibly due to the methodological biases that might affect uncontrolled longitudinal studies.…”

Section: Discussionmentioning

confidence: 99%

Clinical baseline factors predict response to natalizumab: their usefulness in patient selection

Laroni

Gandoglia

Solaro³

et al. 2014

BMC Neurol

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BackgroundOptimal patient selection would improve the risk-benefit ratio of natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS). Clinical features of subjects responding to natalizumab have not been univocally recognized.MethodsLongitudinal data on RR MS patients treated with natalizumab in Liguria, Italy are reported. Predictors of relapse occurrence and disability improvement were analyzed with a logistic regression method in subjects treated for one year (N = 62). A new score, called “Better EDSS Trend (BET)”, was devised to describe the impact of the treatment on disability. Changes in annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two years and proportion of disease-free patients were evaluated.ResultsPrevious EDSS worsening plus ARR ≥ 2 increased the risk of relapse during the treatment [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in disability at one year. EDSS 3.0-3.5 or high disease activity were associated with neurological improvement in the first year of treatment (respectively OR 5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in the disability trend, was observed in 40.3% of patients, and correlated with high ARR in the year before treatment (OR 1.69, P = 0.03).ConclusionSubjects with EDSS 3.0-3.5 and those with very active disease in the year before treatment are most likely to improve in neurological function under natalizumab. A relapse in the first year of treatment is associated to high pre-treatment disease activity; however, since the occurrence of a relapse did not have a negative impact on clinical improvement at one year, we suggest that it should not lead to treatment discontinuation. We propose BET as an additional endpoint of treatment response in MS.

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“…It is therefore comforting that a number of observational studies have confirmed the efficacy of natalizumab reported in clinical trials (Table 1). The duration of treatment was up to 50 months in one case [Fernández et al 2012] and three studies included more than 1000 patients [Fernández et al 2012;Mancardi et al 2011;Piehl et al 2011]. In these studies, the baseline EDSS ranged from 3.1 to 4.0 compared with 2.53 in the AFFIRM trial.…”

Section: Natalizumab In Clinical Practicementioning

confidence: 99%

Best practice in the use of natalizumab in multiple sclerosis

Fernández

2012

Ther Adv Neurol Disord

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Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis who have failed first-line treatment with traditional disease-modifying therapies or who have highly active disease. The drug has proved highly effective, both in a clinical trial setting and in clinical practice, with marked reductions in the rate of clinical relapses and slowed disease progression. These clinical outcomes are mirrored by a marked reduction in disease activity as evidenced by magnetic resonance imaging of the brain. However, natalizumab treatment has been associated with a risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal condition caused by JC virus (JCV) activation. When this condition was detected in a clinical trial shortly after approval, the drug was immediately and voluntarily withdrawn from the market. As a condition of its reinstatement, stringent pharmacovigilance measures and a risk management plan were enforced. The recent availability of a two-step enzyme-linked immunosorbent assay (ELISA) test for the presence of anti-JCV antibodies (free testing is available in a central laboratory for registered centers), along with an ever-improving understanding of other risk factors such as prior immunosuppressant use and duration of treatment, allow an increasingly refined stratification of the risk of PML. This improved stratification of risk can help guide decisions about treatment. This review will also deal with other topics of relevance to clinical practice such as the development of antinatalizumab antibodies and their negative implications in terms of hypersensitivity reactions and loss of efficacy, withdrawal of treatment, and compassionate pediatric use.

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Three years of experience: the Italian registry and safety data update

Cited by 28 publications

References 3 publications

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

Effect of natalizumab on clinical and radiological disease activity in a French cohort of patients with relapsing-remitting multiple sclerosis

Clinical baseline factors predict response to natalizumab: their usefulness in patient selection

Best practice in the use of natalizumab in multiple sclerosis

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