Contributions
Abstract: P882
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: There are currently more than 14 disease modifying treatments (DMTs) approved for relapsing remitting multiple sclerosis (RRMS). Efficacy of individual DMTs has been demonstrated by phase 3 trials; however, the comparative effectiveness of therapies is not well established. The availability of highly effective medications with favorable safety profiles has resulted in a clinical conundrum: whether to use highly effective medications as first line treatment or use a lower or moderately effective medication and escalate based on response.
Objective and aims: Describe the rationale and design of a clinical trial comparing early highly effective therapy (EHT) versus escalation (ESC) approaches in the treatment of early RRMS.
Methods: DELIVER-MS was funded by the Patient Centered Outcomes Research Institute. Development of the study protocol was conducted by the study steering committee with additional input from a group of stakeholders including people with MS (advisory group) and focus groups.
Results: DELIVER-MS is a multi-center pragmatic comparative effectiveness, rater blinded, randomized clinical trial (RCT) with an additional-parallel observational cohort (OBS). The study will recruit 400 treatment naïve people with RRMS into the RCT cohort and up to 400 into the OBS cohort from 12 sites in the United States and 12 sites in the United Kingdom. Participants will be randomized to EHT (choice of alemtuzumab, natalizumab, ocrelizumab, or rituximab) or ESC (any other approved MS DMT) with subsequent DMT changes at participant/clinician discretion. The long-term outcome of interest in the study is disability; however, the first phase of the study is powered to examine a proxy endpoint highly predictive of subsequent disability: brain volume loss from baseline to 36 months. Secondary endpoints will include 6 month to 36 month brain volume loss, disability composite (EDSS and MSFC-4 Components), patient reported outcomes (Neuro-QOL, Multiple Sclerosis Impact Scale 29 [MSIS-29], Patient Health Questionnaire-8 [PHQ-8]), and safety outcomes (serious adverse events, discontinuation, TSQM).
Conclusions: Comparison of treatment approaches in MS is a significant priority. The DELIVER-MS study seeks to determine the comparative effectiveness of EHT and ESC. The study results will have broad implications for a coherent and principled approach to DMT selection for newly diagnosed people with MS.
Disclosure: DO: Funding from PCORI, NIH, NMSS, Race to Erase, Genentech, Genzyme. Consulting from Biogen Idec, Genentech, Genzyme, Merck
ET: Nothing to disclose
KN: received personal fees for speaking from Sanofi Genzyme, and license fee from Biogen; received research funding from NIH, DOD, NMSS, Biogen, Sanofi Genzyme, and Novartis.
SP: Funding from Guthy Jackson Charitable Foundation
DMM: Consulting fees from Hoffman-Roche, Ltd
CH: Dr. Carrie Hersh has received speaking and consulting fees from Genzyme, Teva, Biogen, and Novartis; she has served on advisory committees for Biogen, Teva, and Genentech; Grants- Biogen and Genentech
BZC: Personal fees for consulting and speaking from Genentech and Sanofi-Genzyme
CB: Nothing to disclose
EA: Funding from Acorda, Biogen, Novartis, and Rocky Mountain MS Center. Consulting for Biogen, Celgene, EMD Serono, Genentech, Genzyme, Teva, Novartis, and TG pharmaceuticals
JC: Support from the Efficacy and Mechanism Evaluation Programme and Health Technology Assessment Programme (NIHR); UK Multiple Sclerosis Society and National Multiple Sclerosis Society. Research: Receptos, Novartis, Biogen Idec, and Novartis Advisory Boards/consultancy: Roche, Merck, MedDay, Biogen and Celgene
MC: Nothing to disclose
LF: Nothing to disclose
NF: Nothing to disclose
MDG: Consulting fees: ADAMAS, EMD Serono, Sanofi, Novartis Pharmaceuticals, Teva Neuroscience; research support: Biogen IDEC, National MS Society, NIH, Novartis Pharmaceuticals,PCORI
JH: Nothing to disclose
DH: Nothing to disclose
GH: Research funding: Biogen, Genzyme, Mallinckrodt, MedImmune, Hoffman LaRoche, Novartis; Consulting fees: Biogen, Genzyme
MH: Nothing to disclose
FJ: Nothing to disclose
OL: Nothing to disclose
HM: Nothing to disclose
JN: Nothing to disclose
RN: Consulting: Biogen and Roche
JO: Speakers fees / advisory fees / travel / hospitality: Roche, Biogen, Novartis, Teva, Merck, Medday, Allergan, Celgene, Genzyme. Research : Novartis, Biogen, Roche, Genzyme, Merck
ORP: Honoraria and travel expenses from Biogen, Bayer, Genzyme, Merck, Novartis, Roche and Teva and served on advisory boards for Biogen, Novartis, Merck and Roche
IP: Nothing to disclose
AS: Consulting: advisory board for Genentech and Bayer. Member of the speaker bureau for EMD Serono, Biogen, Genentech, and Genzyme
AZ: Speaking/consulting/advisory board honoraria from Acorda, Biogen, Genentech, Genzyme, Novartis
SG: Nothing to disclose
DG: Nothing to disclose
AC: Nothing to disclose
NL: Nothing to disclose
EG: Nothing to disclose
JAC: Personal fees for consulting from Adamas, Celgene, Convelo, EMD Serono, Novartis, and PendoPharm; speaking for Mylan; and serving as Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
NE: funding and support from PCORI, MS society, Biogen, Novartis, Roche,Teva
Abstract: P882
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: There are currently more than 14 disease modifying treatments (DMTs) approved for relapsing remitting multiple sclerosis (RRMS). Efficacy of individual DMTs has been demonstrated by phase 3 trials; however, the comparative effectiveness of therapies is not well established. The availability of highly effective medications with favorable safety profiles has resulted in a clinical conundrum: whether to use highly effective medications as first line treatment or use a lower or moderately effective medication and escalate based on response.
Objective and aims: Describe the rationale and design of a clinical trial comparing early highly effective therapy (EHT) versus escalation (ESC) approaches in the treatment of early RRMS.
Methods: DELIVER-MS was funded by the Patient Centered Outcomes Research Institute. Development of the study protocol was conducted by the study steering committee with additional input from a group of stakeholders including people with MS (advisory group) and focus groups.
Results: DELIVER-MS is a multi-center pragmatic comparative effectiveness, rater blinded, randomized clinical trial (RCT) with an additional-parallel observational cohort (OBS). The study will recruit 400 treatment naïve people with RRMS into the RCT cohort and up to 400 into the OBS cohort from 12 sites in the United States and 12 sites in the United Kingdom. Participants will be randomized to EHT (choice of alemtuzumab, natalizumab, ocrelizumab, or rituximab) or ESC (any other approved MS DMT) with subsequent DMT changes at participant/clinician discretion. The long-term outcome of interest in the study is disability; however, the first phase of the study is powered to examine a proxy endpoint highly predictive of subsequent disability: brain volume loss from baseline to 36 months. Secondary endpoints will include 6 month to 36 month brain volume loss, disability composite (EDSS and MSFC-4 Components), patient reported outcomes (Neuro-QOL, Multiple Sclerosis Impact Scale 29 [MSIS-29], Patient Health Questionnaire-8 [PHQ-8]), and safety outcomes (serious adverse events, discontinuation, TSQM).
Conclusions: Comparison of treatment approaches in MS is a significant priority. The DELIVER-MS study seeks to determine the comparative effectiveness of EHT and ESC. The study results will have broad implications for a coherent and principled approach to DMT selection for newly diagnosed people with MS.
Disclosure: DO: Funding from PCORI, NIH, NMSS, Race to Erase, Genentech, Genzyme. Consulting from Biogen Idec, Genentech, Genzyme, Merck
ET: Nothing to disclose
KN: received personal fees for speaking from Sanofi Genzyme, and license fee from Biogen; received research funding from NIH, DOD, NMSS, Biogen, Sanofi Genzyme, and Novartis.
SP: Funding from Guthy Jackson Charitable Foundation
DMM: Consulting fees from Hoffman-Roche, Ltd
CH: Dr. Carrie Hersh has received speaking and consulting fees from Genzyme, Teva, Biogen, and Novartis; she has served on advisory committees for Biogen, Teva, and Genentech; Grants- Biogen and Genentech
BZC: Personal fees for consulting and speaking from Genentech and Sanofi-Genzyme
CB: Nothing to disclose
EA: Funding from Acorda, Biogen, Novartis, and Rocky Mountain MS Center. Consulting for Biogen, Celgene, EMD Serono, Genentech, Genzyme, Teva, Novartis, and TG pharmaceuticals
JC: Support from the Efficacy and Mechanism Evaluation Programme and Health Technology Assessment Programme (NIHR); UK Multiple Sclerosis Society and National Multiple Sclerosis Society. Research: Receptos, Novartis, Biogen Idec, and Novartis Advisory Boards/consultancy: Roche, Merck, MedDay, Biogen and Celgene
MC: Nothing to disclose
LF: Nothing to disclose
NF: Nothing to disclose
MDG: Consulting fees: ADAMAS, EMD Serono, Sanofi, Novartis Pharmaceuticals, Teva Neuroscience; research support: Biogen IDEC, National MS Society, NIH, Novartis Pharmaceuticals,PCORI
JH: Nothing to disclose
DH: Nothing to disclose
GH: Research funding: Biogen, Genzyme, Mallinckrodt, MedImmune, Hoffman LaRoche, Novartis; Consulting fees: Biogen, Genzyme
MH: Nothing to disclose
FJ: Nothing to disclose
OL: Nothing to disclose
HM: Nothing to disclose
JN: Nothing to disclose
RN: Consulting: Biogen and Roche
JO: Speakers fees / advisory fees / travel / hospitality: Roche, Biogen, Novartis, Teva, Merck, Medday, Allergan, Celgene, Genzyme. Research : Novartis, Biogen, Roche, Genzyme, Merck
ORP: Honoraria and travel expenses from Biogen, Bayer, Genzyme, Merck, Novartis, Roche and Teva and served on advisory boards for Biogen, Novartis, Merck and Roche
IP: Nothing to disclose
AS: Consulting: advisory board for Genentech and Bayer. Member of the speaker bureau for EMD Serono, Biogen, Genentech, and Genzyme
AZ: Speaking/consulting/advisory board honoraria from Acorda, Biogen, Genentech, Genzyme, Novartis
SG: Nothing to disclose
DG: Nothing to disclose
AC: Nothing to disclose
NL: Nothing to disclose
EG: Nothing to disclose
JAC: Personal fees for consulting from Adamas, Celgene, Convelo, EMD Serono, Novartis, and PendoPharm; speaking for Mylan; and serving as Co-Editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
NE: funding and support from PCORI, MS society, Biogen, Novartis, Roche,Teva