Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study
Abstract Introduction Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-...
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Adis, Springer Healthcare
2024-12-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-024-00680-z |
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| author | Krupa Shah Pandey Kathryn Giles Konstantin Balashov Richard Macdonell Jörg Windsheimer Mikel Martinez Ivan Božin Stephanie Raynaud Matthew Scaramozza Oksana Mokliatchouk Zhaonan Sun Nicholas Belviso Yayoi Sato Xiaochen Lin Annette Okai |
| author_facet | Krupa Shah Pandey Kathryn Giles Konstantin Balashov Richard Macdonell Jörg Windsheimer Mikel Martinez Ivan Božin Stephanie Raynaud Matthew Scaramozza Oksana Mokliatchouk Zhaonan Sun Nicholas Belviso Yayoi Sato Xiaochen Lin Annette Okai |
| author_sort | Krupa Shah Pandey |
| collection | DOAJ |
| description | Abstract Introduction Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.5 years of follow-up. Methods Patients newly prescribed DMF were recruited from 393 sites globally. The primary objective was to assess the incidence and type of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of DMF. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs). Results Overall, 5124 patients received ≥ 1 dose of DMF. The mean (standard deviation [SD]) age at enrollment was 40.0 (11.2) years; 74% of patients were female. Patients received DMF for a mean (SD) duration of 31.0 (22.7) months. Primary reasons for discontinuation were AEs (n = 1237; 24%); the most common were gastrointestinal AEs (n = 469; 9%), blood and lymphatic disorders (n = 218; 4%), and vascular disorders (n = 200; 4%). SAEs occurred in 391 (8%) patients, most commonly infections and infestations (n = 102; 2%). Adjusted ARR declined by 90% (95% confidence interval [CI]: 90–91%; p < 0.0001), from 0.81 (95% CI 0.79–0.84) 12 months before enrollment to 0.08 (95% CI 0.08–0.09) 6 years after enrollment. The estimated proportion of patients free from confirmed disability progression sustained over 48 weeks was 87.0% at month 60. Mean scores for physical and psychological impact, fatigue, health, and productivity remained stable over 5 years. Conclusion DMF demonstrated a safety profile in real-world clinical practice consistent with the known profile of DMF. Relapse rates were low and both ARR and PROs remained stable over time. Trial Registration ClinicalTrials.gov Identifier NCT02047097. |
| format | Article |
| id | doaj-art-c8a77926a491454a96a6751a772ba3b5 |
| institution | Kabale University |
| issn | 2193-8253 2193-6536 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj-art-c8a77926a491454a96a6751a772ba3b52025-01-26T12:58:29ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362024-12-0114124326010.1007/s40120-024-00680-zLong-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM StudyKrupa Shah Pandey0Kathryn Giles1Konstantin Balashov2Richard Macdonell3Jörg Windsheimer4Mikel Martinez5Ivan Božin6Stephanie Raynaud7Matthew Scaramozza8Oksana Mokliatchouk9Zhaonan Sun10Nicholas Belviso11Yayoi Sato12Xiaochen Lin13Annette Okai14Hackensack University Medical Center, Hackensack Meridian School of MedicineCambridge Memorial HospitalChobanian & Avedisian School of Medicine and Boston Medical Center, Boston UniversityDepartment of Neurology, Austin Health, Univ. of MelbournePraxis für Neurologie und PsychiatrieCentre Hospitalier DaxBiogenFormerly: BiogenBiogenBiogenBiogenBiogenBiogenBiogenNorth Texas Institute of Neurology and HeadacheAbstract Introduction Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.5 years of follow-up. Methods Patients newly prescribed DMF were recruited from 393 sites globally. The primary objective was to assess the incidence and type of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of DMF. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs). Results Overall, 5124 patients received ≥ 1 dose of DMF. The mean (standard deviation [SD]) age at enrollment was 40.0 (11.2) years; 74% of patients were female. Patients received DMF for a mean (SD) duration of 31.0 (22.7) months. Primary reasons for discontinuation were AEs (n = 1237; 24%); the most common were gastrointestinal AEs (n = 469; 9%), blood and lymphatic disorders (n = 218; 4%), and vascular disorders (n = 200; 4%). SAEs occurred in 391 (8%) patients, most commonly infections and infestations (n = 102; 2%). Adjusted ARR declined by 90% (95% confidence interval [CI]: 90–91%; p < 0.0001), from 0.81 (95% CI 0.79–0.84) 12 months before enrollment to 0.08 (95% CI 0.08–0.09) 6 years after enrollment. The estimated proportion of patients free from confirmed disability progression sustained over 48 weeks was 87.0% at month 60. Mean scores for physical and psychological impact, fatigue, health, and productivity remained stable over 5 years. Conclusion DMF demonstrated a safety profile in real-world clinical practice consistent with the known profile of DMF. Relapse rates were low and both ARR and PROs remained stable over time. Trial Registration ClinicalTrials.gov Identifier NCT02047097.https://doi.org/10.1007/s40120-024-00680-zDimethyl fumarateReal worldEffectivenessDisease-modifying treatmentMultiple sclerosis |
| spellingShingle | Krupa Shah Pandey Kathryn Giles Konstantin Balashov Richard Macdonell Jörg Windsheimer Mikel Martinez Ivan Božin Stephanie Raynaud Matthew Scaramozza Oksana Mokliatchouk Zhaonan Sun Nicholas Belviso Yayoi Sato Xiaochen Lin Annette Okai Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study Neurology and Therapy Dimethyl fumarate Real world Effectiveness Disease-modifying treatment Multiple sclerosis |
| title | Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study |
| title_full | Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study |
| title_fullStr | Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study |
| title_full_unstemmed | Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study |
| title_short | Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study |
| title_sort | long term safety and effectiveness of dimethyl fumarate in patients with multiple sclerosis treated in routine medical practice final analysis of the esteem study |
| topic | Dimethyl fumarate Real world Effectiveness Disease-modifying treatment Multiple sclerosis |
| url | https://doi.org/10.1007/s40120-024-00680-z |
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