Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial.
OBJECTIVE: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. METHODS: For this randomized...
| Autors principals: | , , , , , , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2012
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| _version_ | 1826279755208458240 |
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| author | Goodin, D Reder, A Ebers, G Cutter, G Kremenchutzky, M Oger, J Langdon, D Rametta, M Beckmann, K DeSimone, T Knappertz, V |
| author_facet | Goodin, D Reder, A Ebers, G Cutter, G Kremenchutzky, M Oger, J Langdon, D Rametta, M Beckmann, K DeSimone, T Knappertz, V |
| author_sort | Goodin, D |
| collection | OXFORD |
| description | OBJECTIVE: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. METHODS: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. RESULTS: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg-treated patients (46.0% among IFNβ-1b 50 μg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. CONCLUSIONS: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. |
| first_indexed | 2024-03-07T00:03:31Z |
| format | Journal article |
| id | oxford-uuid:76c66393-5ea5-4c08-bc6e-b94ee0ce7e5a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:03:31Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:76c66393-5ea5-4c08-bc6e-b94ee0ce7e5a2022-03-26T20:18:34ZSurvival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:76c66393-5ea5-4c08-bc6e-b94ee0ce7e5aEnglishSymplectic Elements at Oxford2012Goodin, DReder, AEbers, GCutter, GKremenchutzky, MOger, JLangdon, DRametta, MBeckmann, KDeSimone, TKnappertz, V OBJECTIVE: To examine the effects of interferon beta (IFNβ)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. METHODS: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFNβ-1b 250 μg and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. RESULTS: After a median of 21.1 years from RCT enrollment, 98.4%(366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFNβ-1b 250 μg showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFNβ-1b 250 μg-treated patients (46.0% among IFNβ-1b 50 μg-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. CONCLUSIONS: There was a significant survival advantage in this cohort of patients receiving early IFNβ-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFNβ-1b benefit on all-cause mortality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. |
| spellingShingle | Goodin, D Reder, A Ebers, G Cutter, G Kremenchutzky, M Oger, J Langdon, D Rametta, M Beckmann, K DeSimone, T Knappertz, V Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title | Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title_full | Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title_fullStr | Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title_full_unstemmed | Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title_short | Survival in MS: a randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. |
| title_sort | survival in ms a randomized cohort study 21 years after the start of the pivotal ifnβ 1b trial |
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