TY - JOUR
T1 - Comparative analysis of MS outcomes in dimethyl fumaratetreated patients relative to propensity matched fingolimod, interferon, glatiramer acetate, or teriflunomide
AU - Spelman, T.
AU - Kalincik, T.
AU - Trojano, M.
AU - Grand'Maison, F.
AU - Izquierdo, G.
AU - Havrdova, E.
AU - Horakova, D.
AU - Lugaresi, A.
AU - Duquette, P.
AU - Grammond, P.
AU - Hupperts, R.
AU - Lechner-Scott, J.
AU - Granella, F.
AU - Petersen, T.
AU - Terzi, M.
AU - Pucci, E.
AU - Sola, P.
AU - Van Pesch, V.
AU - Iuliano, G.
AU - Oreja-Guevara, C.
AU - Boz, C.
AU - Bergamaschi, R.
AU - Slee, M.
AU - Butzkueven, H.
AU - MSBase Investigators
PY - 2016/9
Y1 - 2016/9
N2 - Objective: The objective of this analysis is to compare time to first relapse (TTFR), annualised relapse rate (ARR) and discontinuation outcomes in patients treated with dimethyl fumarate (DMF) pair-wise relative to a propensity matched cohort of eitherfingolimod (FTY), teriflunomide (TERI), interferons (IFN) or glatiramer acetate (GA).Methods: All data were sourced from the MSBase registry. RRMS patients aged ⩾18 yrs at the time of index DMD initiation with ⩾12 mos of pre-baseline follow-up and ⩾6 mos persistence on the index DMD were eligible for the analysis. Propensity score (PS) matching was used to match patients from the DMF group to a comparable patient in the comparator treatment arms on a 1:1 basis. TTFR and time to index DMD discontinuation were analysed using a Kaplan-Meier approach and a marginal Cox model accounting for PS matched pairs. Mean ARRs will be reported by treatment arm and analysed with a Generalised Estimating Equations Poisson model offsetting for treatment exposure time. Event numbers and follow-up time were insufficient to analyse disability progression.Results: A total of 415 DMF initiators (out of overall 434) were successfully matched to 415 FTY patients. There was no difference in risk of first relapse between DMF and FTY (HR 1.15; 95% CI 0.87, 1.51; reference = FTY). DMF was associated with increased risk of discontinuation relative to fingolimod following 6 mos of continuous therapy (HR 2.39; 95% CI 1.78, 3.20). A total of 420, 382, and 256 patient pairs were matched for DMF/IFN,DMF/GA, and DMF/TERI, respectively. DMF was associated with a 26%, 28%, and 34% reduction in the risk of first relapse relative to IFN (HR 0.74; 95% CI 0.57, 0.97), GA (HR 0.72; 95% CI 0.54, 0.95), and TERI (HR 0.66; 95% CI 0.45, 0.99), respectively. DMF was associated with 1.40 times the risk of discontinuation following 6 mos of continuous therapy vs IFNs (HR 1.40; 95% CI 1.07, 1.83). There was no difference in discontinuation rates between DMF vs GA (HR 1.18; 95% CI 0.89, 1.56) or TERI (HR 0.95; 95% CI 0.66, 1.37). Additional data, including ARR, will be presented.Interpretation: DMF was similar to a matched cohort of FTYtreated patients in regards to risk of first relapse. Conversely, DMF was associated with a statistically significant reduction in risk of first relapse relative to IFN, GA, or TERI. DMF was associated with an increased risk of discontinuation relative to FTY and IFN, following 6 months of continuous therapy.
AB - Objective: The objective of this analysis is to compare time to first relapse (TTFR), annualised relapse rate (ARR) and discontinuation outcomes in patients treated with dimethyl fumarate (DMF) pair-wise relative to a propensity matched cohort of eitherfingolimod (FTY), teriflunomide (TERI), interferons (IFN) or glatiramer acetate (GA).Methods: All data were sourced from the MSBase registry. RRMS patients aged ⩾18 yrs at the time of index DMD initiation with ⩾12 mos of pre-baseline follow-up and ⩾6 mos persistence on the index DMD were eligible for the analysis. Propensity score (PS) matching was used to match patients from the DMF group to a comparable patient in the comparator treatment arms on a 1:1 basis. TTFR and time to index DMD discontinuation were analysed using a Kaplan-Meier approach and a marginal Cox model accounting for PS matched pairs. Mean ARRs will be reported by treatment arm and analysed with a Generalised Estimating Equations Poisson model offsetting for treatment exposure time. Event numbers and follow-up time were insufficient to analyse disability progression.Results: A total of 415 DMF initiators (out of overall 434) were successfully matched to 415 FTY patients. There was no difference in risk of first relapse between DMF and FTY (HR 1.15; 95% CI 0.87, 1.51; reference = FTY). DMF was associated with increased risk of discontinuation relative to fingolimod following 6 mos of continuous therapy (HR 2.39; 95% CI 1.78, 3.20). A total of 420, 382, and 256 patient pairs were matched for DMF/IFN,DMF/GA, and DMF/TERI, respectively. DMF was associated with a 26%, 28%, and 34% reduction in the risk of first relapse relative to IFN (HR 0.74; 95% CI 0.57, 0.97), GA (HR 0.72; 95% CI 0.54, 0.95), and TERI (HR 0.66; 95% CI 0.45, 0.99), respectively. DMF was associated with 1.40 times the risk of discontinuation following 6 mos of continuous therapy vs IFNs (HR 1.40; 95% CI 1.07, 1.83). There was no difference in discontinuation rates between DMF vs GA (HR 1.18; 95% CI 0.89, 1.56) or TERI (HR 0.95; 95% CI 0.66, 1.37). Additional data, including ARR, will be presented.Interpretation: DMF was similar to a matched cohort of FTYtreated patients in regards to risk of first relapse. Conversely, DMF was associated with a statistically significant reduction in risk of first relapse relative to IFN, GA, or TERI. DMF was associated with an increased risk of discontinuation relative to FTY and IFN, following 6 months of continuous therapy.
KW - multiple sclerosis (MS)
KW - comparative analysis
KW - dimethyl fumarate (DMF)
UR - http://journals.sagepub.com/doi/pdf/10.1177/1352458516663086
U2 - 10.1177/1352458516663086
DO - 10.1177/1352458516663086
M3 - Meeting Abstract
SN - 1352-4585
VL - 22
SP - 602
EP - 603
JO - Multiple Sclerosis
JF - Multiple Sclerosis
IS - Supp: 3
T2 - 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis
Y2 - 14 September 2016 through 17 September 2016
ER -