The 11-year long-term follow-up study from the randomized BENEFIT CIS trial

Ludwig Kappos, Gilles Edan, Mark S. Freedman, Xavier Montalbán, Hans-Peter Hartung, Bernhard Hemmer, Edward J. Fox, Frederik Barkhof, Sven Schippling, Andrea Schulze, Dirk Pleimes, Christoph Pohl, Rupert Sandbrink, Gustavo Suarez, Eva-Maria Wicklein

Research output: Contribution to journalArticle

Abstract

Objective: To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. ClinicalTrials.gov identifier: NCT01795872. Classification of evidence: This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.
Original languageEnglish
Pages (from-to)978 - 987
Number of pages10
JournalNeurology
Volume87
Issue number10
DOIs
Publication statusPublished - Sep 6 2016
Externally publishedYes

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Therapeutics
Multiple Sclerosis
Interferon beta-1b
Placebos
Chronic Progressive Multiple Sclerosis
Recurrence
Health Resources
Random Allocation
Disease Progression

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kappos, L., Edan, G., Freedman, M. S., Montalbán, X., Hartung, H-P., Hemmer, B., ... Wicklein, E-M. (2016). The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology, 87(10), 978 - 987. https://doi.org/10.1212/WNL.0000000000003078

The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. / Kappos, Ludwig; Edan, Gilles; Freedman, Mark S.; Montalbán, Xavier; Hartung, Hans-Peter; Hemmer, Bernhard; Fox, Edward J.; Barkhof, Frederik; Schippling, Sven; Schulze, Andrea; Pleimes, Dirk; Pohl, Christoph; Sandbrink, Rupert; Suarez, Gustavo; Wicklein, Eva-Maria.

In: Neurology, Vol. 87, No. 10, 06.09.2016, p. 978 - 987.

Research output: Contribution to journalArticle

Kappos, L, Edan, G, Freedman, MS, Montalbán, X, Hartung, H-P, Hemmer, B, Fox, EJ, Barkhof, F, Schippling, S, Schulze, A, Pleimes, D, Pohl, C, Sandbrink, R, Suarez, G & Wicklein, E-M 2016, 'The 11-year long-term follow-up study from the randomized BENEFIT CIS trial', Neurology, vol. 87, no. 10, pp. 978 - 987. https://doi.org/10.1212/WNL.0000000000003078
Kappos L, Edan G, Freedman MS, Montalbán X, Hartung H-P, Hemmer B et al. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology. 2016 Sep 6;87(10):978 - 987. https://doi.org/10.1212/WNL.0000000000003078
Kappos, Ludwig ; Edan, Gilles ; Freedman, Mark S. ; Montalbán, Xavier ; Hartung, Hans-Peter ; Hemmer, Bernhard ; Fox, Edward J. ; Barkhof, Frederik ; Schippling, Sven ; Schulze, Andrea ; Pleimes, Dirk ; Pohl, Christoph ; Sandbrink, Rupert ; Suarez, Gustavo ; Wicklein, Eva-Maria. / The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. In: Neurology. 2016 ; Vol. 87, No. 10. pp. 978 - 987.
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AU - Hemmer, Bernhard

AU - Fox, Edward J.

AU - Barkhof, Frederik

AU - Schippling, Sven

AU - Schulze, Andrea

AU - Pleimes, Dirk

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N2 - Objective: To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. Methods: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Eleven years after randomization, patients were reassessed. Results: Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. Conclusions: Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. ClinicalTrials.gov identifier: NCT01795872. Classification of evidence: This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.

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