Intravenous immunoglobulin versus intravenous methylprednisolone for chronic
inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial.
Author(s): 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; IMC Trial Group.
Collaborators: Nobile-Orazio E, Gallia F, Cocito D, Paolasso I, Jann S, De Toni
Franceschini L, Uncini A, Notturno F, Antonini G, Clemenzi A, Fazio R, Bianchi F,
Schenone A, Fiorina E, Francia A, Pontecorvo S, Pareyson D, Marchesi C, Santoro
L, Manganelli F, Tamburin S, Praitano ML, Cavaletti G, Piatti M, Giannini F,
Greco G, Sabatelli M, Luigetti M, Beghi E, Messina P, Macchia R, Guarnieri C,
Fiorentino B.
Affiliation(s): Department of Translational Medicine, Milan University, 2nd Neurology, IRCCS
Humanitas Clinical Institute, Rozzano, Milan, Italy. eduardo.nobile@unimi.it
Publication date & source: 2012, Lancet Neurol. , 11(6):493-502
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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