Early switch to fingolimod may decrease the risk of disease recurrence after natalizumab interruption

Laroni, Alice; Brogi, Davide; Milesi, V.; Abate, L; Uccelli, Antonio; Mancardi, Gianluigi

doi:10.1177/1352458512468498

Cited by 30 publications

(25 citation statements)

References 7 publications

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“…The only available data derive from case reports and observational studies on MS patients who switched from natalizumab to fingolimod, generally showing a disease reactivation after the switch with few exceptions [16,17,18,19,20,21]. It has been suggested that early fingolimod start (i.e., before the end of the recommended natalizumab 3-month washout interval) might prevent relapse occurrence [22,23].…”

Section: Discussionmentioning

confidence: 99%

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study

Gajofatto

Mr²,

Deotto³

et al. 2014

Eur Neurol

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Background: It is unclear whether natalizumab and fingolimod have analogous efficacy for relapsing-remitting multiple sclerosis (RRMS). Objective: To compare the outcome of RRMS patients treated with either therapy. Methods: RRMS patients treated with natalizumab or fingolimod at Verona Hospital, Italy, were included. The study design was retrospective, based on prospectively collected clinical and MRI data. As efficacy outcomes, time to relapse, relapse rate, expanded disability status scale (EDSS) score change, and new T2/gadolinium-enhancing lesions on brain MRI were compared over treatment period between the two groups. Multivariate Cox and logistic regression models were used to control for potential confounders. Results: Fifty-seven subjects receiving natalizumab and 30 receiving fingolimod for a median duration of 23 (1-63) and 22 (2-35) months, respectively (p = 0.22) were included. Patients treated with natalizumab had a more active pre-treatment disease course compared to those treated with fingolimod. In multivariate analysis, the relapse risk was reduced in patients on natalizumab (Hazard Ratio = 0.33; 95% CI = 0.11-1.03; p = 0.056) compared to those on fingolimod. There was no significant difference in EDSS and MRI outcomes. No relevant unexpected adverse events occurred. One patient discontinued natalizumab for progressive multifocal leukoencephalopathy. Conclusions: RRMS patients receiving natalizumab had higher baseline disease activity and lower relapse risk over 20 months of treatment compared to those receiving fingolimod. Head-to-head randomized clinical trials are needed.

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Section: Discussionmentioning

confidence: 99%

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study

Gajofatto

Mr²,

Deotto³

et al. 2014

Eur Neurol

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“…De Seze et al observed a reduction in the proportion of clinical relapses in patients who had started FTY within three months of discontinuing NAT compared to patients who had started FTY more than three months after NAT suspension [25]. The benefits of FTY after NAT compared to interferon beta-1a or glatiramer acetate or no treatment is also described in a small series by Laroni et al [26]. The French multicentre observational study ENIGM (Enquete Nationale concernant l'Introduction du fingolimod en relais au natalizumab) observed a clinical relapse in 27% of patients during the washout period from NAT to FTY, perhaps reflecting a poor control of disease activity during NAT treatment; in fact, only 39% of patients stopped NAT exclusively for safety reasons [27].…”

Section: Discussionmentioning

confidence: 99%

Second-Line Therapy with Fingolimod for Relapsing-Remitting Multiple Sclerosis in Clinical Practice: The Effect of Previous Exposure to Natalizumab

et al. 2014

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Background: To evaluate efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis, particularly in patients previously exposed to natalizumab. Method: Prospective observational single-centre second-line cohort study. Results: Among 71 patients treated with fingolimod 0.5 mg/day for a mean duration of 21.75 w 12.60 months, the annualized relapse rate was 0.66 (C.I. 95% 0.27-1.05) with a significant difference between 26 patients with prior natalizumab exposure (1.15; C.I. 95% 0.12-2.17) and 45 not exposed (0.38; C.I. 95% 0.18-0.57; p = 0.002). In a multivariate negative regression model, only previous exposure to natalizumab (p = 0.049) and duration of fingolimod treatment (p < 0.001) significantly correlated with the annualized relapse rate. Previous exposure to natalizumab (p = 0.028) and duration of treatment with fingolimod (p < 0.001) were confirmed by restricting the analysis to the first 12 months of treatment with fingolimod, but were no longer statistically significant by analysing only patients (n = 51) with at least 12 months of treatment with fingolimod (0.32; C.I. 95% 0.08-0.55 vs. 0.22; C.I. 95% 0.11-0.32; p = NS). No differences were observed in neuroradiological outcomes and disability progression in patients exposed to natalizumab and not exposed. The rate of discontinuation due to adverse events was 11.3%, with no differences between the two groups. Conclusions: Our study confirms efficacy and side effects of fingolimod in a second-line clinical practice cohort. Prior natalizumab exposure and duration of treatment with fingolimod are independent predictors of annualized relapse rate during the first 12 months of treatment with fingolimod, but not in the long-term, and may be influenced by the 3 months washout period between the two drugs. i 2014 S. Karger AG, Basel

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“…Other studies have also reported a considerable risk of reactivation following fingolimod use after NTZ [17,18,19,20,21]. Exceptions to these findings have been observed for shorter time intervals to switching NTZ, pointing out the importance of early initiation of alternate treatment in reducing the risk of recurrence of disease [11,22,23,24]. Recent evidence with newer oral therapies is clear in showing that switching from NTZ to dimethyl fumarate results in increased relapses [25].…”

Section: Introductionmentioning

confidence: 99%

Observational Study of Switching from Natalizumab to Immunomodulatory Drugs

et al. 2017

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Objective: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). Methods: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months. Results: Twelve months after switching from NTZ to DMDs, there were no significant differences in the annualized relapse rate (ARR) compared to the days that NTZ was used (0.3 vs. 0.1; p = 0.083); and the ARR never reached similar values to those prior to NTZ use (1.61; p < 0.001). The percentage of relapse-free patients after switching from NTZ was 71.4%. These patients did not have lower disease activity before NTZ compared with those with clinical relapses (1.3 vs. 1.7; p = 0.302), but they had lower Expanded Disability Status Scale scores (3.4 vs. 5.7; p = 0.001). DMDs had beneficial effects on MRI parameters, as 10 of 16 patients (62.5%) presented no evidence of radiological activity 12 months after NTZ discontinuation. Conclusions: Patients with RRMS and moderate disability who discontinued NTZ for safety reasons may benefit from the DMDs GA and interferon with no known risk for progressive multifocal leukoencephalopathy.

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Early switch to fingolimod may decrease the risk of disease recurrence after natalizumab interruption

Abstract: Figure 1. Relapses (black bars) occurring during observation in untreated subjects (U1-U4), subjects who shifted to other immunomodulatory drugs (IM1-IM4) or to fingolimod (F1-F11).

Cited by 30 publications

References 7 publications

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study

Are Natalizumab and Fingolimod Analogous Second-Line Options for the Treatment of Relapsing-Remitting Multiple Sclerosis? A Clinical Practice Observational Study

Second-Line Therapy with Fingolimod for Relapsing-Remitting Multiple Sclerosis in Clinical Practice: The Effect of Previous Exposure to Natalizumab

Observational Study of Switching from Natalizumab to Immunomodulatory Drugs

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