Abstract: P594
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a favourable benefit-risk profile in clinical trials and real-world analyses. Radiological measures such as T1 black hole conversion and annual changes in brain atrophy may be used as a marker for improved clinical outcomes for patients. ENDORSE, an ongoing extension study of the original pivotal trials, allows assessment of the impact of long-term DMF treatment.
Objectives: Report radiological outcomes in patients with relapsing remitting multiple sclerosis (RRMS) treated long-term with DMF in ENDORSE.
Methods: Patients from the MRI cohort of DEFINE/CONFIRM who continued DMF treatment in ENDORSE were included (BID-BID, PBO-DMF, GA-DMF). MRI scans were obtained yearly. The first ENDORSE MRI was performed at the end of year 1; therefore, only data from year 1 forward were analysed. For analysis of new hypointense T1 and hyperintense T2 lesions, only patients with a yearly scan for 5 years were included (completer analysis); data are reported by year of exposure to DMF. For the percent brain volume change (PBVC) analysis, all patients regardless of number of scans were included due to sample size restrictions; data are reported by year of ENDORSE.
Results: Of the 530 ENDORSE MRI cohort patients, 209 were included in the completer analysis; 116 patients newly initiated treatment with DMF in ENDORSE and 93 were previously treated with DMF. When analysed annually, most patients revealed no new hypointense lesions on T1: Year 1-2: 83/116 (72%); Year 2-3: 79/116 (68%); Year 3-4: 145/209 (69%); Year 4-5: 146/209 (70%); Year 5-6: 65/93 (70%); Year 6-7: 67/93 (72%). The annual rate of new/newly enlarging T2 lesions was also positively affected by DMF treatment. For the PBVC analysis, 134 BID-BID patients were included. After 2 prior years of DMF treatment, the adjusted mean yearly PBVC at end of ENDORSE year 2 was -0.22 (n=134); year 3: -0.28 (n=116); year 4: -0.37 (n=114); year 5: -0.22 (n=108); year 6: -0.19 (n=89).
Conclusions: The data suggest that long-term DMF treatment translates into meaningful benefits of tissue protection on MRI: a low frequency of new T1 hypointense lesions, suggesting axonal preservation; annual changes in brain volume approaching that of healthy individuals; and, a low annual rate of new/newly enlarging T2 lesions consistent with maintained anti-inflammatory effects. These findings indicate that DMF provides long-term efficacy for RRMS patients.
Supported by: Biogen
Disclosure: Douglas L. Arnold reports consultant fees and/or grants from Acorda, Adelphi, Alkermes, Biogen, Celgene, Genentech, Genzyme, Hoffman LaRoche, Immune Tolerance Network, Immunotec, MedDay Pharmaceuticals, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis, Canadian Institutes of Health Research, MS Society of Canada, International Progressive MS Alliance, and equity interest in NeuroRx Research.
Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products.The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Ralf Gold honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders.
Chongshu Chen: employee of and holds stock/stock options in Biogen.
Lili Yang: employee of and holds stock/stock options in Biogen.
Catherine Miller: employee of and holds stock/stock options in Biogen..
Abstract: P594
Type: Poster Sessions
Abstract Category: Therapy - Long-term treatment monitoring
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a favourable benefit-risk profile in clinical trials and real-world analyses. Radiological measures such as T1 black hole conversion and annual changes in brain atrophy may be used as a marker for improved clinical outcomes for patients. ENDORSE, an ongoing extension study of the original pivotal trials, allows assessment of the impact of long-term DMF treatment.
Objectives: Report radiological outcomes in patients with relapsing remitting multiple sclerosis (RRMS) treated long-term with DMF in ENDORSE.
Methods: Patients from the MRI cohort of DEFINE/CONFIRM who continued DMF treatment in ENDORSE were included (BID-BID, PBO-DMF, GA-DMF). MRI scans were obtained yearly. The first ENDORSE MRI was performed at the end of year 1; therefore, only data from year 1 forward were analysed. For analysis of new hypointense T1 and hyperintense T2 lesions, only patients with a yearly scan for 5 years were included (completer analysis); data are reported by year of exposure to DMF. For the percent brain volume change (PBVC) analysis, all patients regardless of number of scans were included due to sample size restrictions; data are reported by year of ENDORSE.
Results: Of the 530 ENDORSE MRI cohort patients, 209 were included in the completer analysis; 116 patients newly initiated treatment with DMF in ENDORSE and 93 were previously treated with DMF. When analysed annually, most patients revealed no new hypointense lesions on T1: Year 1-2: 83/116 (72%); Year 2-3: 79/116 (68%); Year 3-4: 145/209 (69%); Year 4-5: 146/209 (70%); Year 5-6: 65/93 (70%); Year 6-7: 67/93 (72%). The annual rate of new/newly enlarging T2 lesions was also positively affected by DMF treatment. For the PBVC analysis, 134 BID-BID patients were included. After 2 prior years of DMF treatment, the adjusted mean yearly PBVC at end of ENDORSE year 2 was -0.22 (n=134); year 3: -0.28 (n=116); year 4: -0.37 (n=114); year 5: -0.22 (n=108); year 6: -0.19 (n=89).
Conclusions: The data suggest that long-term DMF treatment translates into meaningful benefits of tissue protection on MRI: a low frequency of new T1 hypointense lesions, suggesting axonal preservation; annual changes in brain volume approaching that of healthy individuals; and, a low annual rate of new/newly enlarging T2 lesions consistent with maintained anti-inflammatory effects. These findings indicate that DMF provides long-term efficacy for RRMS patients.
Supported by: Biogen
Disclosure: Douglas L. Arnold reports consultant fees and/or grants from Acorda, Adelphi, Alkermes, Biogen, Celgene, Genentech, Genzyme, Hoffman LaRoche, Immune Tolerance Network, Immunotec, MedDay Pharmaceuticals, Novartis, Pfizer, Receptos, Roche, Sanofi-Aventis, Canadian Institutes of Health Research, MS Society of Canada, International Progressive MS Alliance, and equity interest in NeuroRx Research.
Ludwig Kappos' Institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the Department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, sanofi-aventis, Santhera, Teva, Vianex and royalties for Neurostatus-UHB products.The Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Ralf Gold honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders.
Chongshu Chen: employee of and holds stock/stock options in Biogen.
Lili Yang: employee of and holds stock/stock options in Biogen.
Catherine Miller: employee of and holds stock/stock options in Biogen..