Contributions
Abstract: P1184
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: To date there is no comparative study on the real-world effectiveness and tolerability of interferon beta-1a (IFN β-1a) subcutaneously (SC) three times weekly (tiw) and dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). Real-world studies can explore medical needs of patients (pts) in a more naturalistic setting and broader population than randomised controlled trials.
Objective: To evaluate the proportion of pts who demonstrate no medical need to discontinue therapy (Tx) among disease-modifying drug (DMD)-naïve pts with RRMS after 1 year of Tx with IFN β-1a 44 µg SC tiw or DMF 240 mg twice daily. No medical need to discontinue Tx will be measured by the primary endpoint, which is a composite of (1) no evidence of disease activity (NEDA-2), defined as no relapses, no new or enlarging T2 lesions, and no T1 gadolinium-enhancing lesions, and (2) no discontinuation due to disease activity, tolerability, or adverse events.
Methods: This ongoing, Phase IV, retrospective, magnetic resonance imaging (MRI)-reader-blinded, longitudinal, cohort study will examine data from medical records and high-quality MRI scans of around 5400 pts from about 50 US MS treatment centres. Included pts will have a diagnosis of RRMS or clinically isolated syndrome; be aged 18-55 years; have initiated Tx with IFN β-1a SC tiw or DMF (index date); and have no prior DMD use. All eligible pts will be enrolled consecutively, regardless of their outcome, in reverse chronological order starting with those whose index date is 15 months before study launch. Enrolment will continue until each Tx group includes 400 pts who have MRI scans available at baseline and 1 year post-index and remained on initial Tx at the 1-year scan. To mitigate potential selection bias, groups will be stratified by propensity scores derived from pts" baseline characteristics. Propensity score matching will also be explored. Each component of the composite primary endpoint will also be evaluated individually as secondary endpoints. This study is designed for estimation rather than hypothesis confirmation. 90% confidence intervals will be reported.
Results: Enrolment began on 1 March 2016. Interim analysis results will be available in Q3 2016, with final results expected by end of 2016.
Conclusions: By examining clinical and MRI data in pts stratified by propensity scores, this trial design allows for rapid analysis of large cohorts for real-world effectiveness and tolerability outcomes.
Disclosure: Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health, and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus, and IMS Health.
Choon Cha is an employee of EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Guy Buckle received research support from Biogen and personal fees for consulting and/or speaking from Bayer, Biogen, EMD Serono, Inc. (a business of Merck KGaA, Darmstadt, Germany), Genentech Pharmaceuticals, Genzyme, Mallinckrodt, Novartis, , and Teva.
Julie Aldridge is an employee of EMD Serono Research & Development Institute, Billerica, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Gabriele Haas is employed by IMS Health, which is executing the study on behalf of the sponsor. Neither GH nor IMS Health have any conflict of interest regarding the outcome of the study.
Josh Reed is an employee of EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Bruce Hughes received research support from Acorda, Bayer HealthCare, Biogen, EMD Serono, Inc. (a business of Merck KGaA, Darmstadt, Germany), Genzyme, Novartis, Pfizer, and Teva Pharmaceuticals.
Abstract: P1184
Type: Poster
Abstract Category: Therapy - disease modifying - Immunomodulation/Immunosuppression
Background: To date there is no comparative study on the real-world effectiveness and tolerability of interferon beta-1a (IFN β-1a) subcutaneously (SC) three times weekly (tiw) and dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS). Real-world studies can explore medical needs of patients (pts) in a more naturalistic setting and broader population than randomised controlled trials.
Objective: To evaluate the proportion of pts who demonstrate no medical need to discontinue therapy (Tx) among disease-modifying drug (DMD)-naïve pts with RRMS after 1 year of Tx with IFN β-1a 44 µg SC tiw or DMF 240 mg twice daily. No medical need to discontinue Tx will be measured by the primary endpoint, which is a composite of (1) no evidence of disease activity (NEDA-2), defined as no relapses, no new or enlarging T2 lesions, and no T1 gadolinium-enhancing lesions, and (2) no discontinuation due to disease activity, tolerability, or adverse events.
Methods: This ongoing, Phase IV, retrospective, magnetic resonance imaging (MRI)-reader-blinded, longitudinal, cohort study will examine data from medical records and high-quality MRI scans of around 5400 pts from about 50 US MS treatment centres. Included pts will have a diagnosis of RRMS or clinically isolated syndrome; be aged 18-55 years; have initiated Tx with IFN β-1a SC tiw or DMF (index date); and have no prior DMD use. All eligible pts will be enrolled consecutively, regardless of their outcome, in reverse chronological order starting with those whose index date is 15 months before study launch. Enrolment will continue until each Tx group includes 400 pts who have MRI scans available at baseline and 1 year post-index and remained on initial Tx at the 1-year scan. To mitigate potential selection bias, groups will be stratified by propensity scores derived from pts" baseline characteristics. Propensity score matching will also be explored. Each component of the composite primary endpoint will also be evaluated individually as secondary endpoints. This study is designed for estimation rather than hypothesis confirmation. 90% confidence intervals will be reported.
Results: Enrolment began on 1 March 2016. Interim analysis results will be available in Q3 2016, with final results expected by end of 2016.
Conclusions: By examining clinical and MRI data in pts stratified by propensity scores, this trial design allows for rapid analysis of large cohorts for real-world effectiveness and tolerability outcomes.
Disclosure: Robert Zivadinov received personal compensation from Teva Pharmaceuticals, Biogen Idec, EMD Serono, Genzyme-Sanofi, Claret Medical, IMS Health, and Novartis for speaking and consultant fees. He received financial support for research activities from Teva Pharmaceuticals, Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus, and IMS Health.
Choon Cha is an employee of EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Guy Buckle received research support from Biogen and personal fees for consulting and/or speaking from Bayer, Biogen, EMD Serono, Inc. (a business of Merck KGaA, Darmstadt, Germany), Genentech Pharmaceuticals, Genzyme, Mallinckrodt, Novartis, , and Teva.
Julie Aldridge is an employee of EMD Serono Research & Development Institute, Billerica, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Gabriele Haas is employed by IMS Health, which is executing the study on behalf of the sponsor. Neither GH nor IMS Health have any conflict of interest regarding the outcome of the study.
Josh Reed is an employee of EMD Serono, Inc., Rockland, MA, USA (a business of Merck KGaA, Darmstadt, Germany).
Bruce Hughes received research support from Acorda, Bayer HealthCare, Biogen, EMD Serono, Inc. (a business of Merck KGaA, Darmstadt, Germany), Genzyme, Novartis, Pfizer, and Teva Pharmaceuticals.