Intravenous immunoglobulin for people with chronic inflammatory demyelinating polyradiculoneuropathy

Review question

We performed this review to assess the evidence from randomised trials on how effective and safe intravenous immunoglobulin (IVIg) is for people with CIDP.

Background

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an illness in which nerves become inflamed and this leads to paralysis. The likely cause is that the body attacks its own nerves. CIDP usually requires long-term treatment to prevent further disability. There is much debate about the first choice of treatment. One choice is a medicine called immunoglobulin, which is a product made from purified antibodies from human donor blood and which is given via injection into a vein. Steroid drugs and plasma exchange (a treatment in which the plasma element of a person's blood is replaced), are known to be effective.

Study characteristics

Eight randomised controlled trials including 332 participants with CIDP were eligible for this review. These compared IVIg with placebo (dummy treatment), plasma exchange, or steroid drugs.

Key results and quality of the evidence

We found five randomised trials which together prove that IVIg improves disability more than placebo (dummy treatment). The results showed that three people would need to be treated for one person to improve. In the three trials that compared IVIg with other treatments, results with IVIg were similar to plasma exchange, oral prednisolone or intravenous methylprednisolone. The evidence was of moderate or high quality. In this review, there were mild and short-term side effects in around half of those who received IVIg. Six per cent of those treated with IVIg had serious side effects, which is a similar rate as with plasma exchange or corticosteroids.

Each trial defined improvement in its own way and the trials used different measurement scales, so it is difficult to relate them to changes in the clinical condition of people with CIDP. Only one of the studies that compared IVIg with placebo had a long-term follow-up. It suggested that IVIg improves disability more than placebo over 24 weeks and possibly 48 weeks. Further research is needed to compare the long-term benefits as well as side effects of IVIg with other treatments.

The most recent search for studies was in December 2012 and we updated the review with the results of one additional trial.

Authors' conclusions: 

The evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of three. During this period it has similar efficacy to plasma exchange, oral prednisolone and intravenous methylprednisolone. In one large trial, the benefit of IVIg persisted for 24 and possibly 48 weeks. Further research is needed to compare the long-term benefits as well as side effects of IVIg with other treatments.

Read the full abstract...
Background: 

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. This review was first published in 2002 and has since been updated, most recently in 2013.

Objectives: 

To review systematically the evidence from randomised controlled trials (RCTs) concerning the efficacy and safety of IVIg in CIDP.

Search strategy: 

On 4 December 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, issue 11 in the Cochrane Library), MEDLINE and EMBASE to December 2012 and ISI from January 1985 to May 2008. We searched for ongoing trials through two metaRegistries (World Health Organization International Clinical Trials Registry Platform Search Portal and Current Controlled Trials).

Selection criteria: 

We selected RCTs testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP.

Data collection and analysis: 

Two authors reviewed literature searches to identify potentially relevant RCTs, scored their quality and extracted data independently. We contacted authors for additional information.

Main results: 

We considered eight RCTs, including 332 participants, to be eligible for inclusion in the review. These trials were homogeneous and the overall risk of bias low. Five studies, in a total of 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange, one trial compared IVIg with prednisolone in 32 participants, and one trial, newly included at this update, compared IVIg with intravenous methylprednisolone in 46 participants.

A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome 3.03 (95% CI 2.33 to 4.55), high quality evidence). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials, including 84 participants, the disability score could be transformed to the modified Rankin score, on which improvement of one point after IVIg treatment compared to placebo was barely significant (RR 2.40, 95% CI 0.98 to 5.83) (moderate quality evidence). Only one placebo-controlled study included in this review had a long-term follow-up. The results of this study suggest that IVIg improves disability more than placebo over 24 and 48 weeks.

The mean disability score revealed no significant difference between IVIg and plasma exchange at six weeks (moderate quality evidence). There was no significant difference in improvement in disability on prednisolone compared with IVIg after two or six weeks, or on methylprednisolone compared to IVIg after two weeks or six months (moderate quality evidence).

There were no statistically significant differences in frequencies of side effects between the three types of treatment for which data were available (IVg versus placebo or steroids). (moderate or high quality evidence) Mild and transient adverse events were found in 49% of participants treated with IVIg, while serious adverse events were found in six per cent.

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