Elsevier

The Lancet Neurology

Volume 11, Issue 6, June 2012, Pages 493-502
The Lancet Neurology

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

https://doi.org/10.1016/S1474-4422(12)70093-5Get rights and content

Summary

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.

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing neuropathy,1, 2 with a prevalence ranging from 0·8 to 8·4 per 100 000 people.3, 4 CIDP is often disabling with over 50% of patients having temporary disability and about 10% eventually becoming persistently disabled or dying because of the disease.5

The cause of CIDP remains unknown, but there are data supporting an immune pathogenesis.6 These data have led to the use of immune therapies, the efficacy of which has reinforced the hypothesis of an autoimmune origin. A few randomised trials and several uncontrolled studies on a large series of patients have shown the efficacy of corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIg) in CIDP.7, 8, 9 Two randomised trials on a small population of patients showed a comparable short-term efficacy of IVIg and oral corticosteroids10 and of IVIg and plasma exchange.11 Little is known about the efficacy of these therapies over the long term. In a large randomised trial, IVIg was more efficacious than placebo for 6 months and possibly up to 12 months,12, 13 whereas a similar chance of remission was seen over 12 months with the use of either daily oral corticosteroids or pulsed high-dose dexamethasone.14 The comparative efficacy and tolerance of IVIg or corticosteroids over this period remains unclear. We compared the efficacy and tolerability of 6-month therapy with IVIg or intravenous methylprednisolone in patients with CIDP.

Section snippets

Patients

In this multicentre, randomised, double-blind, placebo controlled, parallel-group study, patients with CIDP were enrolled from 14 Italian neurological centres. Patients were eligible if they were at least 18 years of age, had definite typical CIDP according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) criteria,15 had some disability (scoring 2 or more on either the overall neuropathy limitation scale [ONLS]16 or the modified Rankin scale17), were in

Results

46 patients were enrolled between September, 2007, and December, 2009. A patient assigned to IVIg was later excluded since he had received high-dose intravenous corticosteroids 2 months before inclusion (figure 1). 21 patients were treated with intravenous methylprednisolone and 24 with IVIg. Compared with patients in the IVIg group, those in the methylprednisolone group tended to have a worse median Rankin scale score and ONLS score, to be older, to report less frequent use of IVIg, and to

Discussion

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. Assessment scores showed that responses tended to be more favourable in the IVIg group, possibly reflecting the different drop-out rate in the two groups; however, these data should be interpreted with caution because of the large number of comparisons for which no adjustment was made.

The small sample size

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