Contributions
Abstract: P665
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) and fingolimod (FNG) are two approved oral drugs for relapsing-remitting multiple sclerosis (RRMS). Although the European Medicine Agency recommends different indications for DMF and FNG, both drugs are sometime used either as switch strategy in patients who do not respond to self-injectable drugs or as first treatment option. However, real world data reporting direct comparison of their effectiveness are still scarce.
Objective: To directly compare the effectiveness of DMF and FNG in achieving the No Evidence of Disease Activity (NEDA-3) status, defined as absence of relapses, disability worsening and magnetic resonance imaging activity.
Methods: We analyzed data of patients with RRMS regularly attending 7 MS Clinics in Central Italy and who started DMF or FNG as first treatment (naïves) or were switched from a self-injectable drugs (switchers). To be included, patients were required to have had at least one relapse in the year prior to DMF or FNG start, no previous exposure to either monoclonal antibodies or immunosuppressants, minimum 3-month persistence on DMF and FNG. Since patients were not randomized to treatment group, we performed a propensity score (PS)-based nearest neighbour matching within a calliper of 0.05 to select only patients with similar baseline characteristics. Pairwise comparisons were then conducted in matched samples using a Cox proportional hazards model (stratified by Centre) with the NEDA-3 as main outcome. Pairwise censoring was adopted to adjust for difference in length of follow-up among the two treatment groups.
Results: Overall, 426 and 469 patients started DMF and FNG, respectively. There was significant imbalance in pre-matching baseline characteristics across treatment groups, due to the lower EDSS score, fewer pre-treatment relapses and active MRI scans in DMF group (p-values< 0.001). A total of 550 patients (275 per group) was retained by the PS-matching procedure. After a median on-study follow-up of 18 months, we found a trend toward a better outcome (NEDA-3) for FNG over DMF (HR=0.76, p=0.07). Subgroup analyses showed a comparable effectiveness of the two drugs in naïves (n=198; HR=0.88, p=0.96), while FNG was superior to DMF in the achievement of NEDA-3 status in switchers (n=352; HR=0.62, p=0.02).
Discussion: Our study suggests that DMF is as effective as FNG in naïve patients, while FNG could be a better option for patients switching from a self-injectable drug.
Disclosure:
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
ML: nothing to disclose.
PB: funding for travel or speaker honoraria from Biogen, Novartis and Sanofi-Genzyme.
AB: nothing to disclose.
FB: advisory board membership of Teva and Merck Serono; honoraria for speaking or consultation fees from Almirall, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva.
DC: advisory Board membership of Almirall, Bayer Schering, Biogen, Genzyme, GW Pharmaceuticals, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi, Teva; principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi, Teva; preclinical and clinical research supported by grants from Bayer, Biogen, Merck Serono, Novartis e Teva.
AC: honoraria for speaking and travel grants from Biogen, Sanofi-Genzyme and Teva.
LDG: travel grants from Biogen, Novartis, and Teva
RF: honoraria for speaking or consultation fees from Almirall, Merck Serono, Novartis, Sanofi, Teva, Biogen; advisory board membership of Teva, Biogen, Merck Serono, Novartis.
EF: advisory board membership and/or travel grants from Merck Serono. Sanofi-Genzyme and Teva.
AF: advisory board membership or honoraria for speaking from Novartis and Teva.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
GAM: advisory Board membership of Biogen, Genzyme, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva; principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi, Teva.
VN: nothing to disclose.
SP: honoraria for speaking from Almirall, Biogen, Teva, and Genzyme; travel grants from CSL Behring, Genzyme, Novartis, Teva, Kedrion.
CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi, Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi and Teva.
SR: speaking honoraria from Merck Serono and Teva.
MS: consulting fees and/or honoraria for speaking and/or research grants from Biogen, Genzyme, Merck Serono, Novartis, Roche and Teva.
ES: nothing to disclose.
MM: scientific advisory board membership of Bayer Schering, Biogen, Sanofi-Genzyme, Merck-Serono, Novartis, Teva; consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Ultragenix; principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, Ultragenix.
Abstract: P665
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Delayed-release dimethyl fumarate (DMF) and fingolimod (FNG) are two approved oral drugs for relapsing-remitting multiple sclerosis (RRMS). Although the European Medicine Agency recommends different indications for DMF and FNG, both drugs are sometime used either as switch strategy in patients who do not respond to self-injectable drugs or as first treatment option. However, real world data reporting direct comparison of their effectiveness are still scarce.
Objective: To directly compare the effectiveness of DMF and FNG in achieving the No Evidence of Disease Activity (NEDA-3) status, defined as absence of relapses, disability worsening and magnetic resonance imaging activity.
Methods: We analyzed data of patients with RRMS regularly attending 7 MS Clinics in Central Italy and who started DMF or FNG as first treatment (naïves) or were switched from a self-injectable drugs (switchers). To be included, patients were required to have had at least one relapse in the year prior to DMF or FNG start, no previous exposure to either monoclonal antibodies or immunosuppressants, minimum 3-month persistence on DMF and FNG. Since patients were not randomized to treatment group, we performed a propensity score (PS)-based nearest neighbour matching within a calliper of 0.05 to select only patients with similar baseline characteristics. Pairwise comparisons were then conducted in matched samples using a Cox proportional hazards model (stratified by Centre) with the NEDA-3 as main outcome. Pairwise censoring was adopted to adjust for difference in length of follow-up among the two treatment groups.
Results: Overall, 426 and 469 patients started DMF and FNG, respectively. There was significant imbalance in pre-matching baseline characteristics across treatment groups, due to the lower EDSS score, fewer pre-treatment relapses and active MRI scans in DMF group (p-values< 0.001). A total of 550 patients (275 per group) was retained by the PS-matching procedure. After a median on-study follow-up of 18 months, we found a trend toward a better outcome (NEDA-3) for FNG over DMF (HR=0.76, p=0.07). Subgroup analyses showed a comparable effectiveness of the two drugs in naïves (n=198; HR=0.88, p=0.96), while FNG was superior to DMF in the achievement of NEDA-3 status in switchers (n=352; HR=0.62, p=0.02).
Discussion: Our study suggests that DMF is as effective as FNG in naïve patients, while FNG could be a better option for patients switching from a self-injectable drug.
Disclosure:
LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme.
ML: nothing to disclose.
PB: funding for travel or speaker honoraria from Biogen, Novartis and Sanofi-Genzyme.
AB: nothing to disclose.
FB: advisory board membership of Teva and Merck Serono; honoraria for speaking or consultation fees from Almirall, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva.
DC: advisory Board membership of Almirall, Bayer Schering, Biogen, Genzyme, GW Pharmaceuticals, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi, Teva; principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi, Teva; preclinical and clinical research supported by grants from Bayer, Biogen, Merck Serono, Novartis e Teva.
AC: honoraria for speaking and travel grants from Biogen, Sanofi-Genzyme and Teva.
LDG: travel grants from Biogen, Novartis, and Teva
RF: honoraria for speaking or consultation fees from Almirall, Merck Serono, Novartis, Sanofi, Teva, Biogen; advisory board membership of Teva, Biogen, Merck Serono, Novartis.
EF: advisory board membership and/or travel grants from Merck Serono. Sanofi-Genzyme and Teva.
AF: advisory board membership or honoraria for speaking from Novartis and Teva.
SG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Almirall, Sanofi-Aventis, Novartis, Genzyme.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
GAM: advisory Board membership of Biogen, Genzyme, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva; principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi, Teva.
VN: nothing to disclose.
SP: honoraria for speaking from Almirall, Biogen, Teva, and Genzyme; travel grants from CSL Behring, Genzyme, Novartis, Teva, Kedrion.
CP: scientific advisory boards for Actelion, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi, Teva; consulting and/or speaking fees, research support and travel grants from Allergan, Almirall, Biogen, Genzyme, Hoffmann-La Roche Ltd, Merck-Serono, Novartis, Sanofi and Teva.
SR: speaking honoraria from Merck Serono and Teva.
MS: consulting fees and/or honoraria for speaking and/or research grants from Biogen, Genzyme, Merck Serono, Novartis, Roche and Teva.
ES: nothing to disclose.
MM: scientific advisory board membership of Bayer Schering, Biogen, Sanofi-Genzyme, Merck-Serono, Novartis, Teva; consulting and/or speaking fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Ultragenix; principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, Ultragenix.