Comparative effectiveness of delayed-release dimethyl fumarate vs. other disease-modifying therapies in patients with multiple sclerosis: a network meta-analysis of real-world evidence
ECTRIMS Online Library. Cutter G. 09/13/19; 278594; P1394
Gary Cutter
Gary Cutter
Contributions
Abstract

Abstract: P1394

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

G. Cutter1, M.P. Sormani2, M. Betts3, S. Nambiar3, K. Fahrbach3, G. Sarri4, M. Rock5, T. Debray6

1University of Alabama at Birmingham School of Public Health, Birmingham, AL, United States, 2University of Genoa Department of Health Sciences, Genoa, Italy, 3Evidera, Waltham, MA, United States, 4Evidera, London, United Kingdom, 5Biogen, Cambridge, MA, United States, 6University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands

Introduction: Real-world evidence (RWE) is increasingly recognised as a valuable source of information in capturing the patient experience in clinical practice, despite concerns of confounding bias. This is true in chronic conditions with heterogeneous populations and expanded treatment options, such as multiple sclerosis. However, propensity scores and multivariate methods can help alleviate bias in RWE. Network meta-analyses (NMA) pool these adjusted results, which averages effects and provides additional comparisons.
Objective: To estimate the comparative effectiveness of dimethyl fumarate (DMF) vs. disease-modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS) via NMAs of RWE.
Methods: MEDLINE and Embase were systematically searched in February 2019 for large comparative RWE studies with ≥85% RRMS populations. Eligible studies reported results adjusting for known confounders (e.g. age, disease burden) with at least one-year of follow-up for annualised relapse rate (ARR), time to first relapse (TTFR), confirmed disability progression (CDP). A Bayesian NMA was conducted using OpenBUGS v3.2.3. NMA was also conducted in groups based on prior treatment status and sensitivity analyses explored the impact of including low-quality studies and heterogeneous populations.
Results: 61 publications reporting on 21 databases were identified; 19 databases provided data for the NMA. In random-effects models, DMF showed greater effectiveness in reducing ARR and delaying TTFR vs. interferons (IFN) (rate ratio [RR] [95% credible interval]: 0.73 [0.57,0.91]; hazard ratio [HR]: 0.69 [0.55,0.86]), glatiramer acetate (GA; RR: 0.72 [0.58,0.88]; HR: 0.71 [0.58,0.88]), and teriflunomide (TERI; RR: 0.69 [0.56,0.84]; HR: 0.64 [0.52,0.78]), and demonstrated comparable effectiveness vs. fingolimod (FTY). However, alemtuzumab (ALEM; RR: 1.81 [1.15,2.92]) and natalizumab (NTZ; RR: 1.44 [1.01,2.17]) had greater effectiveness than DMF in reducing ARR; comparisons were not available for TTFR. Results were generally consistent in subgroups stratified according to prior treatment status. CDP results and sensitivity analyses exploring heterogeneity and inconsistency will be reported.
Conclusions: RWE NMAs suggest that, for RRMS pts, DMF is significantly more effective than GA, IFN, and TERI, and comparable to FTY, but not ALEM, and NTZ in reducing ARR and delaying TTFR. This NMA minimised confounding inherent to RWE by selecting robust, adjusted studies.
Disclosure: MB, SN, KF, GS received funding from Biogen. The authors had full editorial control over the submitted abstract. MR is an employee of Biogen. MPS, TD, and GC previously received funding from Biogen. MPS, TD, and GC have performed consultancy services for Biogen, and served in advisory board panels.

Abstract: P1394

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

G. Cutter1, M.P. Sormani2, M. Betts3, S. Nambiar3, K. Fahrbach3, G. Sarri4, M. Rock5, T. Debray6

1University of Alabama at Birmingham School of Public Health, Birmingham, AL, United States, 2University of Genoa Department of Health Sciences, Genoa, Italy, 3Evidera, Waltham, MA, United States, 4Evidera, London, United Kingdom, 5Biogen, Cambridge, MA, United States, 6University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands

Introduction: Real-world evidence (RWE) is increasingly recognised as a valuable source of information in capturing the patient experience in clinical practice, despite concerns of confounding bias. This is true in chronic conditions with heterogeneous populations and expanded treatment options, such as multiple sclerosis. However, propensity scores and multivariate methods can help alleviate bias in RWE. Network meta-analyses (NMA) pool these adjusted results, which averages effects and provides additional comparisons.
Objective: To estimate the comparative effectiveness of dimethyl fumarate (DMF) vs. disease-modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS) via NMAs of RWE.
Methods: MEDLINE and Embase were systematically searched in February 2019 for large comparative RWE studies with ≥85% RRMS populations. Eligible studies reported results adjusting for known confounders (e.g. age, disease burden) with at least one-year of follow-up for annualised relapse rate (ARR), time to first relapse (TTFR), confirmed disability progression (CDP). A Bayesian NMA was conducted using OpenBUGS v3.2.3. NMA was also conducted in groups based on prior treatment status and sensitivity analyses explored the impact of including low-quality studies and heterogeneous populations.
Results: 61 publications reporting on 21 databases were identified; 19 databases provided data for the NMA. In random-effects models, DMF showed greater effectiveness in reducing ARR and delaying TTFR vs. interferons (IFN) (rate ratio [RR] [95% credible interval]: 0.73 [0.57,0.91]; hazard ratio [HR]: 0.69 [0.55,0.86]), glatiramer acetate (GA; RR: 0.72 [0.58,0.88]; HR: 0.71 [0.58,0.88]), and teriflunomide (TERI; RR: 0.69 [0.56,0.84]; HR: 0.64 [0.52,0.78]), and demonstrated comparable effectiveness vs. fingolimod (FTY). However, alemtuzumab (ALEM; RR: 1.81 [1.15,2.92]) and natalizumab (NTZ; RR: 1.44 [1.01,2.17]) had greater effectiveness than DMF in reducing ARR; comparisons were not available for TTFR. Results were generally consistent in subgroups stratified according to prior treatment status. CDP results and sensitivity analyses exploring heterogeneity and inconsistency will be reported.
Conclusions: RWE NMAs suggest that, for RRMS pts, DMF is significantly more effective than GA, IFN, and TERI, and comparable to FTY, but not ALEM, and NTZ in reducing ARR and delaying TTFR. This NMA minimised confounding inherent to RWE by selecting robust, adjusted studies.
Disclosure: MB, SN, KF, GS received funding from Biogen. The authors had full editorial control over the submitted abstract. MR is an employee of Biogen. MPS, TD, and GC previously received funding from Biogen. MPS, TD, and GC have performed consultancy services for Biogen, and served in advisory board panels.

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