Mariko Kita1, Robert J Fox2, Ralf Gold3, Gavin Giovannoni4, J Theodore Phillips5, Sujata P Sarda6, Jessica Kong6, Vissia Viglietta6, Sarah I Sheikh6, Macaulay Okwuokenye6, Ludwig Kappos7. 1. Neuroscience Institute, Virginia Mason Medical Center, Seattle, Washington. Electronic address: mariko.kita@virginiamason.org. 2. Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio. 3. Department of Neurology, Saint Josef-Hospital/Ruhr-University Bochum, Bochum, Germany. 4. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. 5. Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, Texas. 6. Biogen Idec Inc, Cambridge, Massachusetts. 7. Departments of Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland.
Abstract
PURPOSE:Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. METHODS:Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. FINDINGS: The integrated analysis included 2301 patients treated with delayed-release DMF BID (n = 769) or TID (n = 761) orplacebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMF BID and TID groups compared with placebo. SF-36subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMF BID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-release DMF treatment, lower baseline EDSS score, age ≤40 years (PCS only), and corresponding lower baseline PCS or MCS score. Changes from baseline in VAS and EuroQoL-5D scores were generally consistent with changes in SF-36 scores. IMPLICATIONS: These HRQoL benefits parallel the improvements in clinical and magnetic resonance imaging end points with delayed-release DMF, suggesting that delayed-release DMF treatment improves patient-perceived health status as well as neurologic and physical functioning. ClinicalTrials.gov identifiers: NCT0042012; NCT00451451.
RCT Entities:
PURPOSE: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. METHODS:Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. FINDINGS: The integrated analysis included 2301 patients treated with delayed-release DMFBID (n = 769) or TID (n = 761) or placebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMFBID and TID groups compared with placebo. SF-36 subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMFBID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-release DMF treatment, lower baseline EDSS score, age ≤40 years (PCS only), and corresponding lower baseline PCS or MCS score. Changes from baseline in VAS and EuroQoL-5D scores were generally consistent with changes in SF-36 scores. IMPLICATIONS: These HRQoL benefits parallel the improvements in clinical and magnetic resonance imaging end points with delayed-release DMF, suggesting that delayed-release DMF treatment improves patient-perceived health status as well as neurologic and physical functioning. ClinicalTrials.gov identifiers: NCT0042012; NCT00451451.
Authors: Amber Salter; Samantha Lancia; Gary Cutter; Robert J Fox; Ruth Ann Marrie; Jason P Mendoza; James B Lewin Journal: Int J MS Care Date: 2021-07-09
Authors: Qin Wang; Sergei Chuikov; Sophina Taitano; Qi Wu; Arjun Rastogi; Samuel J Tuck; Joseph M Corey; Steven K Lundy; Yang Mao-Draayer Journal: Int J Mol Sci Date: 2015-06-17 Impact factor: 5.923