Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study
Background: Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. Obj...
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SAGE Publishing
2025-02-01
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| Series: | Therapeutic Advances in Neurological Disorders |
| Online Access: | https://doi.org/10.1177/17562864241306575 |
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| author | Tjalf Ziemssen Ann D. Bass Bart Van Wijmeersch Sara Eichau Stephan Richter Frank Hoffmann Nicole M. Armstrong Magdalena Chirieac Janete Cunha-Santos Barry A. Singer |
| author_facet | Tjalf Ziemssen Ann D. Bass Bart Van Wijmeersch Sara Eichau Stephan Richter Frank Hoffmann Nicole M. Armstrong Magdalena Chirieac Janete Cunha-Santos Barry A. Singer |
| author_sort | Tjalf Ziemssen |
| collection | DOAJ |
| description | Background: Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. Objectives: To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13 years of TOPAZ data and TREAT-MS interim data. Design: TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12 mg/day, 3 consecutive days; ⩾12 months apart) for 11–13 years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4 years after last alemtuzumab treatment phase. Methods: Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (⩾2 relapses in the year prior to baseline and ⩾1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed. Results: More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3–13) and in TREAT-MS (0.24, > 2 years). Stable/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS. Conclusion: Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals. Trial registration: ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281). |
| format | Article |
| id | doaj-art-7501220d9792407a9d9288ee81c7f4e6 |
| institution | Kabale University |
| issn | 1756-2864 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SAGE Publishing |
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| series | Therapeutic Advances in Neurological Disorders |
| spelling | doaj-art-7501220d9792407a9d9288ee81c7f4e62025-02-10T18:03:30ZengSAGE PublishingTherapeutic Advances in Neurological Disorders1756-28642025-02-011810.1177/17562864241306575Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world studyTjalf ZiemssenAnn D. BassBart Van WijmeerschSara EichauStephan RichterFrank HoffmannNicole M. ArmstrongMagdalena ChirieacJanete Cunha-SantosBarry A. SingerBackground: Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS. Objectives: To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13 years of TOPAZ data and TREAT-MS interim data. Design: TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12 mg/day, 3 consecutive days; ⩾12 months apart) for 11–13 years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4 years after last alemtuzumab treatment phase. Methods: Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (⩾2 relapses in the year prior to baseline and ⩾1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed. Results: More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3–13) and in TREAT-MS (0.24, > 2 years). Stable/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS. Conclusion: Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals. Trial registration: ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281).https://doi.org/10.1177/17562864241306575 |
| spellingShingle | Tjalf Ziemssen Ann D. Bass Bart Van Wijmeersch Sara Eichau Stephan Richter Frank Hoffmann Nicole M. Armstrong Magdalena Chirieac Janete Cunha-Santos Barry A. Singer Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study Therapeutic Advances in Neurological Disorders |
| title | Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study |
| title_full | Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study |
| title_fullStr | Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study |
| title_full_unstemmed | Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study |
| title_short | Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study |
| title_sort | long term efficacy and safety of alemtuzumab in participants with highly active ms topaz clinical trial and interim analysis of treat ms real world study |
| url | https://doi.org/10.1177/17562864241306575 |
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