Contributions
Abstract: P642
Type: Poster Sessions
Abstract Category: Therapy - Others
Background: Patients with multiple sclerosis (MS) on long-term injectable therapies may suffer from the so-called “needle fatigue” (i.e. a waning commitment to continue with the prescribed injectable treatment), due to a variety of different factors, including difficulties with injections, anxiety/depression, or inaccurate beliefs about the MS disease process.
Objective: To directly compare switching to dimethyl fumarate (DMF), teriflunomide (TRF) or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up.
Methods: In this multicentre post-marketing study we considered 488 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (n=266), TRF (n=121), or PEG (n=101) due to needle fatigue. Since patients were not randomized to treatment group, we performed a 1:1:1 ratio propensity score (PS)-based matching procedure (calliper of 0.1, no replacement). According to the common-referent approach, we derived two separate PS using logistic regressions to estimate the conditional probability to receive DMF vs. PEG and TRF vs. PEG. Pairs of subjects with overlapping PS in DMF and TRF groups were then matched. Time to discontinuation and time to first relapse were explored in matched samples by Cox regression models, adjusted for sex and age, and stratified by matched cases.
Results: There was significant imbalance in pre-matching baseline characteristics across treatment groups, due to older age, longer time since first symptom, and higher EDSS score in TRF group (p-values< 0.001). The PS-based matching procedure retained 180 patients (60 per group). At follow-up, 7 (12%), 13 (22%) and 24 (40%) discontinued TRF, DMF and PEG, respectively. Switching to PEG was associated with a greater risk of discontinuation when compared to TRF (HR=5.1, p=0.003), but not when compared to DMF (HR=1.9, p=0.10). There was no significant difference between DMF and TRF (HR=2.4, p=0.12). The highest discontinuation rate observed in PEG recipient was mainly due to poor tolerability. The low number of patients who relapsed over the 12-month follow-up (10 out of 180 analyzed, approximately 5%) prevented any analysis on the short-term risk of relapse.
Discussion: This real-world study suggests that oral drugs, especially TRF, are a better switching option than low-frequency interferon for promoting the short-term treatment persistence in stable patients who do not tolerate injectable drugs.
Disclosure: LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, 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.
AC: speaker honoraria from Biogen; travel grants from Biogen, Merck, Sanofi Genzyme, Teva; advisory boards member honoraria from Biogen, Merck, Novartis, Teva.
ML: travel grants from Biogen and Sanofi-Genzyme; speaker honoraria from Biogen.
SP: speaker honoraria from Biogen, Novartis, Teva.
LB: travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
GB: research grants from Almirall and Merck-Serono.
MCB: advisory board membership and honoraria for speaking from Teva, Novartis, Sanofi, Merck Serono and Biogen.
FC: travel support from CSL Behring GmbH, Genzyme, Biogen, and Merck Serono.
CDF: speaking fees and travel grants from Biogen, Sanofi-Genzyme, Merck Serono.
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: speaker honoraria from Merck, Teva; travel grants from Biogen, Merck, Sanofi Genzyme, Teva; advisory boards member honoraria from Sanofi, Merck, Novartis, Teva.
MMF: nothing to disclose.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon and research grants from Italian Minister of Foreign Affairs.
DL: travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva.
GM: travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen.
FM: received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
DC: advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
GAM: advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva.
EM: speaking honoraria and/or travel grants from Teva, Merck, Biogen, Novartis, Genzyme, Roche, Almirall.
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.
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.
MS: speaking honoraria and research support from Biogen, Novartis, Teva, Sanofi Genzyme, Merck, Roche.
CT: honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
GDB: speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis and Bayer Shering Pharma; support for participation to Congresses from Bayer-Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis and Teva.
Abstract: P642
Type: Poster Sessions
Abstract Category: Therapy - Others
Background: Patients with multiple sclerosis (MS) on long-term injectable therapies may suffer from the so-called “needle fatigue” (i.e. a waning commitment to continue with the prescribed injectable treatment), due to a variety of different factors, including difficulties with injections, anxiety/depression, or inaccurate beliefs about the MS disease process.
Objective: To directly compare switching to dimethyl fumarate (DMF), teriflunomide (TRF) or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up.
Methods: In this multicentre post-marketing study we considered 488 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (n=266), TRF (n=121), or PEG (n=101) due to needle fatigue. Since patients were not randomized to treatment group, we performed a 1:1:1 ratio propensity score (PS)-based matching procedure (calliper of 0.1, no replacement). According to the common-referent approach, we derived two separate PS using logistic regressions to estimate the conditional probability to receive DMF vs. PEG and TRF vs. PEG. Pairs of subjects with overlapping PS in DMF and TRF groups were then matched. Time to discontinuation and time to first relapse were explored in matched samples by Cox regression models, adjusted for sex and age, and stratified by matched cases.
Results: There was significant imbalance in pre-matching baseline characteristics across treatment groups, due to older age, longer time since first symptom, and higher EDSS score in TRF group (p-values< 0.001). The PS-based matching procedure retained 180 patients (60 per group). At follow-up, 7 (12%), 13 (22%) and 24 (40%) discontinued TRF, DMF and PEG, respectively. Switching to PEG was associated with a greater risk of discontinuation when compared to TRF (HR=5.1, p=0.003), but not when compared to DMF (HR=1.9, p=0.10). There was no significant difference between DMF and TRF (HR=2.4, p=0.12). The highest discontinuation rate observed in PEG recipient was mainly due to poor tolerability. The low number of patients who relapsed over the 12-month follow-up (10 out of 180 analyzed, approximately 5%) prevented any analysis on the short-term risk of relapse.
Discussion: This real-world study suggests that oral drugs, especially TRF, are a better switching option than low-frequency interferon for promoting the short-term treatment persistence in stable patients who do not tolerate injectable drugs.
Disclosure: LP: consulting fees from Biogen, Novartis and Roche; speaker honoraria from Almirall, 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.
AC: speaker honoraria from Biogen; travel grants from Biogen, Merck, Sanofi Genzyme, Teva; advisory boards member honoraria from Biogen, Merck, Novartis, Teva.
ML: travel grants from Biogen and Sanofi-Genzyme; speaker honoraria from Biogen.
SP: speaker honoraria from Biogen, Novartis, Teva.
LB: travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
GB: research grants from Almirall and Merck-Serono.
MCB: advisory board membership and honoraria for speaking from Teva, Novartis, Sanofi, Merck Serono and Biogen.
FC: travel support from CSL Behring GmbH, Genzyme, Biogen, and Merck Serono.
CDF: speaking fees and travel grants from Biogen, Sanofi-Genzyme, Merck Serono.
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: speaker honoraria from Merck, Teva; travel grants from Biogen, Merck, Sanofi Genzyme, Teva; advisory boards member honoraria from Sanofi, Merck, Novartis, Teva.
MMF: nothing to disclose.
SH: consulting fees, speaker honoraria and travel grants from Biogen, Genzyme, Teva, CSL Behrig, Zambon and research grants from Italian Minister of Foreign Affairs.
DL: travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva.
GM: travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen.
FM: received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
DC: advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva.
CG: fees as invited speaker or travel expenses for attending meeting from Biogen, Merck-Serono, Teva, Sanofi, Novartis, Genzyme.
GAM: advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva; honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva.
EM: speaking honoraria and/or travel grants from Teva, Merck, Biogen, Novartis, Genzyme, Roche, Almirall.
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.
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.
MS: speaking honoraria and research support from Biogen, Novartis, Teva, Sanofi Genzyme, Merck, Roche.
CT: honoraria for speaking and travel grant from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis.
GDB: speaker honoraria from Merck Serono, Biogen, Sanofi-Aventis and Bayer Shering Pharma; support for participation to Congresses from Bayer-Schering, Biogen, Merck Serono, Novartis, Sanofi-Aventis and Teva.