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

Dipartimento di Neuroscienze, Oftalmologia e Genetica, Università degli Studi di Genova, Genova, Italy.
Neurological Sciences (Impact Factor: 1.45). 01/2011; 31 Suppl 3(3):295-7. DOI: 10.1007/s10072-010-0356-8
Source: PubMed


At the end of 2006, a pharmacovigilance program on natalizumab was settled by the Italian Pharmaceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was documented.

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Available from: Luigi Maria Edoardo Grimaldi
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    • "In this study, we followed a cohort of MS patients treated with natalizumab for one to two years, with the aim of identifying the best markers of response to the treatment and defining the characteristics of responders. 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. "
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    ABSTRACT: Background Optimal 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. Methods Longitudinal 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. Results Previous 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). Conclusion Subjects 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.
    Full-text · Article · May 2014 · BMC Neurology
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    • "Disregarding potential effects of D Vitamin dietary or childhood hygienic changes, race and latitude, we would prefer to propose that increased population concern about MS symptoms, referral and access to neurological expertise and, recently, to technology acting on stable MSIs might account for the entire EEA pattern, particularly due to the increasing proportion of women active in non-domestic occupational work among those of working age in EEA-surveyed populations. The geographically and time-related decreasing differences in MSI in the EEA by asymptotic trend towards an incidence of 5-7 per 100,000, may suggest that MS appears to behave invariantly with respect to time and space at a stage characterised by improvements in diagnosis and treatment, and by the loss of the natural history due to the widespread use of immune-modulatory treatments that are partly effective and not free of side-effects [70,71]. MS diagnostic functions at EEA might mirror the parallel logarithmic or sigmoid functions outlined in Figure  6. "
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    ABSTRACT: Background A debate surrounding multiple sclerosis epidemiology has centred on time-related incidence increases and the need of monitoring. The purpose of this study is to reassess multiple sclerosis incidence in the European Economic Area. Methods We conducted a systematic review of literature from 1965 onwards and integrated elements of original research, including requested or completed data by surveys authors and specific analyses. Results The review of 5323 documents yielded ten studies for age- and sex-specific analyses, and 21 studies for time-trend analysis of single data sets. After 1985, the incidence of multiple sclerosis ranged from 1.12 to 6.96 per 100,000 population, was higher in females, tripled with latitude, and doubled with study midpoint year. The north registered increasing trends from the 1960s and 1970s, with a historic drop in the Faroe Islands, and fairly stable data in the period 1980-2000; incidence rose in Italian and French populations in the period 1970-2000, in Evros (Greece) in the 1980s, and in the French West Indies in around 2000. Conclusions We conclude that the increase in multiple sclerosis incidence is only apparent, and that it is not specific to women. Monitoring of multiple sclerosis incidence might be appropriate for the European Economic Area.
    Full-text · Article · Jun 2013 · BMC Neurology
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    • "Given that the case of suspected PML was later confirmed, the incidence of PML in our study was 0.15%. This is somewhat higher than in an Italian observational study of the safety data which reported a rate of 0.03% [13] but lower than the 0.27% reported by a surveillance study in Sweden [15]. "
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    ABSTRACT: Natalizumab has been shown to be effective in pivotal clinical trials in multiple sclerosis; however, the patients in whom treatment is indicated in clinical practice have a different clinical profile from those included in the clinical trials. The aim of this study is therefore to collect data on natalizumab use in everyday clinical practice in Spain. The 86 participating centers throughout Spain submitted data on disease characteristics at baseline and after treatment. Valid data were available for 1,364 patients (69.3% women, 86.9% with relapsing-remitting disease). Ninety-three percent had received prior therapy for multiple sclerosis. For the 825 patients on treatment for at least a year, the annualized relapse rate (ARR) decreased from median 2.0 [mean 2.01, 95% confidence interval (CI) 1.92-2.11] in the year prior to natalizumab to 0.0 (mean 0.25, 95% CI 0.21-0.29) at 1 year (p < 0.001). The Expanded Disability Status Scale (EDSS) score decreased from median 3.5 at baseline (mean 3.71, 95% CI 3.60-3.82) to 3.0 (mean 3.37, 95% CI 3.25-3.49) (p < 0.0001). The discontinuation rate was 14%. One patient discontinued natalizumab due to progressive multifocal leukoencephalopathy (PML) and another due to probable PML (subsequently confirmed). Although our patients had more severe disease than those in the pivotal study, a similar reduction in ARR was observed. This finding is in line with previous observational studies. The effect was independent of baseline EDSS.
    Full-text · Article · Jan 2012 · Journal of Neurology
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