Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

Mads Ravnborg, Per Soelberg Sørensen, Magnus Andersson, Elisabeth G Celius, Peter J Jongen, Irina Elovaara, Emmanuel Bartholomé, Cris S Constantinescu, Karsten Beer, Ellen Garde, Bjørn Sperling

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. INTERPRETATION: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. FUNDING: Biogen Idec.
OriginalsprogEngelsk
TidsskriftLancet Neurology Network
Vol/bind9
Udgave nummer7
Sider (fra-til)672-80
Antal sider9
ISSN1470-8582
DOI
StatusUdgivet - 1. jul. 2010

Fingeraftryk

Relapsing-Remitting Multiple Sclerosis
Multicenter Studies
Placebos
Physicians
Neurology
Pharmaceutical Preparations
Adrenal Cortex Hormones

Citer dette

Ravnborg, Mads ; Sørensen, Per Soelberg ; Andersson, Magnus ; Celius, Elisabeth G ; Jongen, Peter J ; Elovaara, Irina ; Bartholomé, Emmanuel ; Constantinescu, Cris S ; Beer, Karsten ; Garde, Ellen ; Sperling, Bjørn. / Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. I: Lancet Neurology Network. 2010 ; Bind 9, Nr. 7. s. 672-80.
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abstract = "BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95{\%} CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. INTERPRETATION: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. FUNDING: Biogen Idec.",
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author = "Mads Ravnborg and S{\o}rensen, {Per Soelberg} and Magnus Andersson and Celius, {Elisabeth G} and Jongen, {Peter J} and Irina Elovaara and Emmanuel Bartholom{\'e} and Constantinescu, {Cris S} and Karsten Beer and Ellen Garde and Bj{\o}rn Sperling",
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Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. / Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus; Celius, Elisabeth G; Jongen, Peter J; Elovaara, Irina; Bartholomé, Emmanuel; Constantinescu, Cris S; Beer, Karsten; Garde, Ellen; Sperling, Bjørn.

I: Lancet Neurology Network, Bind 9, Nr. 7, 01.07.2010, s. 672-80.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

AU - Ravnborg, Mads

AU - Sørensen, Per Soelberg

AU - Andersson, Magnus

AU - Celius, Elisabeth G

AU - Jongen, Peter J

AU - Elovaara, Irina

AU - Bartholomé, Emmanuel

AU - Constantinescu, Cris S

AU - Beer, Karsten

AU - Garde, Ellen

AU - Sperling, Bjørn

N1 - Copyright 2010 Elsevier Ltd. All rights reserved.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. INTERPRETATION: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. FUNDING: Biogen Idec.

AB - BACKGROUND: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis. METHODS: In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766. FINDINGS: 341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group. INTERPRETATION: Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients. FUNDING: Biogen Idec.

KW - Adjuvants, Immunologic

KW - Adult

KW - Disability Evaluation

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Interferon-beta

KW - Kaplan-Meiers Estimate

KW - Longitudinal Studies

KW - Male

KW - Methylprednisolone

KW - Middle Aged

KW - Multiple Sclerosis, Relapsing-Remitting

KW - Neuroprotective Agents

KW - Severity of Illness Index

KW - Treatment Outcome

U2 - 10.1016/S1474-4422(10)70132-0

DO - 10.1016/S1474-4422(10)70132-0

M3 - Journal article

VL - 9

SP - 672

EP - 680

JO - Lancet Neurology Network

JF - Lancet Neurology Network

SN - 1470-8582

IS - 7

ER -