Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: A randomised controlled trial

Eduardo Nobile-Orazio, Dario Cocito, Stefano Jann, Antonino Uncini, Ettore Beghi, Paolo Messina, Giovanni Antonini, Raffaella Fazio, Francesca Gallia, Angelo Schenone, Ada Francia, Davide Pareyson, Lucio Santoro, Stefano Tamburin, Roberta Macchia, Guido Cavaletti, Fabio Giannini, Mario Sabatelli

Research output: Contribution to journalArticle

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Abstract

Background: Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk-benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone. Methods: We did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0·5 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0·5 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76. Findings: 45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52%] of 21) than IVIg (three [13%] of 24; relative risk 0·54, 95% CI 0·34-0·87; p=0·0085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7·7, 95% CI 1·7-33·9; p=0·0070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67%] of 21) and the IVIg group (11 [46%] of 24; p=0·1606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38%] of 21) than did those on methylprednisolone (none of ten; p=0·0317). Interpretation: Treatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies. Funding: Kedrion.

Original languageEnglish
Pages (from-to)493-502
Number of pages10
JournalThe Lancet Neurology
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2012

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Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Intravenous Immunoglobulins
Methylprednisolone
Randomized Controlled Trials
Therapeutics
Random Allocation
Sodium Chloride

ASJC Scopus subject areas

  • Clinical Neurology

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Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy : A randomised controlled trial. / Nobile-Orazio, Eduardo; Cocito, Dario; Jann, Stefano; Uncini, Antonino; Beghi, Ettore; Messina, Paolo; Antonini, Giovanni; Fazio, Raffaella; Gallia, Francesca; Schenone, Angelo; Francia, Ada; Pareyson, Davide; Santoro, Lucio; Tamburin, Stefano; Macchia, Roberta; Cavaletti, Guido; Giannini, Fabio; Sabatelli, Mario.

In: The Lancet Neurology, Vol. 11, No. 6, 06.2012, p. 493-502.

Research output: Contribution to journalArticle

Nobile-Orazio, E, Cocito, D, Jann, S, Uncini, A, Beghi, E, Messina, P, Antonini, G, Fazio, R, Gallia, F, Schenone, A, Francia, A, Pareyson, D, Santoro, L, Tamburin, S, Macchia, R, Cavaletti, G, Giannini, F & Sabatelli, M 2012, 'Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: A randomised controlled trial', The Lancet Neurology, vol. 11, no. 6, pp. 493-502. https://doi.org/10.1016/S1474-4422(12)70093-5
Nobile-Orazio, Eduardo ; Cocito, Dario ; Jann, Stefano ; Uncini, Antonino ; Beghi, Ettore ; Messina, Paolo ; Antonini, Giovanni ; Fazio, Raffaella ; Gallia, Francesca ; Schenone, Angelo ; Francia, Ada ; Pareyson, Davide ; Santoro, Lucio ; Tamburin, Stefano ; Macchia, Roberta ; Cavaletti, Guido ; Giannini, Fabio ; Sabatelli, Mario. / Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy : A randomised controlled trial. In: The Lancet Neurology. 2012 ; Vol. 11, No. 6. pp. 493-502.
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abstract = "Background: Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk-benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone. Methods: We did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0·5 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0·5 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76. Findings: 45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52{\%}] of 21) than IVIg (three [13{\%}] of 24; relative risk 0·54, 95{\%} CI 0·34-0·87; p=0·0085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7·7, 95{\%} CI 1·7-33·9; p=0·0070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67{\%}] of 21) and the IVIg group (11 [46{\%}] of 24; p=0·1606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38{\%}] of 21) than did those on methylprednisolone (none of ten; p=0·0317). Interpretation: Treatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies. Funding: Kedrion.",
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TY - JOUR

T1 - Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy

T2 - A randomised controlled trial

AU - Nobile-Orazio, Eduardo

AU - Cocito, Dario

AU - Jann, Stefano

AU - Uncini, Antonino

AU - Beghi, Ettore

AU - Messina, Paolo

AU - Antonini, Giovanni

AU - Fazio, Raffaella

AU - Gallia, Francesca

AU - Schenone, Angelo

AU - Francia, Ada

AU - Pareyson, Davide

AU - Santoro, Lucio

AU - Tamburin, Stefano

AU - Macchia, Roberta

AU - Cavaletti, Guido

AU - Giannini, Fabio

AU - Sabatelli, Mario

PY - 2012/6

Y1 - 2012/6

N2 - Background: Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk-benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone. Methods: We did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0·5 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0·5 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76. Findings: 45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52%] of 21) than IVIg (three [13%] of 24; relative risk 0·54, 95% CI 0·34-0·87; p=0·0085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7·7, 95% CI 1·7-33·9; p=0·0070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67%] of 21) and the IVIg group (11 [46%] of 24; p=0·1606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38%] of 21) than did those on methylprednisolone (none of ten; p=0·0317). Interpretation: Treatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies. Funding: Kedrion.

AB - Background: Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk-benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone. Methods: We did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0·5 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0·5 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76. Findings: 45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52%] of 21) than IVIg (three [13%] of 24; relative risk 0·54, 95% CI 0·34-0·87; p=0·0085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7·7, 95% CI 1·7-33·9; p=0·0070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67%] of 21) and the IVIg group (11 [46%] of 24; p=0·1606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38%] of 21) than did those on methylprednisolone (none of ten; p=0·0317). Interpretation: Treatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies. Funding: Kedrion.

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