Second-line therapy with fingolimod for relapsing-remitting multiple sclerosis in clinical practice: the effect of previous exposure to natalizumab.
BACKGROUND
To evaluate efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis, particularly in patients previously exposed to natalizumab.


METHODS
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 ± 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.
Institute of Neurology, Catholic University, Rome, Italy.
Assunta
A
Bianco
Agata Katia
AK
Patanella
Viviana
V
Nociti
Alessandro
A
Marti
Giovanni
G
Frisullo
Domenico
D
Plantone
Chiara
C
De Fino
Anna
A
Fetta
Anna Paola
AP
Batocchi
Paolo Maria
PM
Rossini
Massimiliano
M
Mirabella
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D000068876:Fingolimod Hydrochloride