Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome

doi:10.1016/S0140-6736(96)09095-2

The Lancet

Volume 349, Issue 9047, 25 January 1997, Pages 225-230

https://doi.org/10.1016/S0140-6736(96)09095-2 Get rights and content

Summary

Background

The relative efficacy of plasma exchange (PE) and intravenous immunoglobulin (IVIg) for the treatment of Guillain-Barré syndrome has not been established. We compared PE with IVIg, and with a combined regimen of PE followed by IVIg, in an international, multicentre, randomised trial of 383 adult patients with Guillain-Barré syndrome.

Methods

The patients were randomly assigned PE (five 50 mL/kg exchanges over 8-13 days), IVIg (Sandoglobulin, 0·4 g/kg daily for 5 days), or the PE course immediately followed by the IVIg course. The inclusion criteria were severe disease (aid needed for walking) and onset of neuropathic symptoms within the previous 14 days. Patients were followed up for 48 weeks.

Findings

Four patients were excluded because they did not meet the randomisation criteria. All the remaining 379 patients were assessed for the major outcome criterion—change on a seven-point disability grade scale—by an observer unaware of treatment assignment, 4 weeks after randomisation. At that time, the mean improvement was 0·9 (SD 1·3) in the 121 PE-group patients, 0·8 (1·3) in the 130 IVIg-group patients, and 1·1 (1·4) in the 128 patients who received both treatments (intention-to-treat analysis). None of the differences between the groups for this major outcome criterion was significant. The difference between PE alone and IVIg alone was so small that a 0·5 grade difference was excluded at the 95% level of confidence. There was no significant difference between any of the treatment groups in the secondary outcome measures: time to recovery of unaided walking, time to discontinuation of ventilation, and trend describing the recovery from disability up to 48 weeks. There was a non-significant trend towards a more favourable outcome on some outcome measures with combined treatment.

Interpretation

In treatment of severe Guillain-Barré syndrome during the first 2 weeks after onset of neuropathic symptoms, PE and IVIg had equivalent efficacy. The combination of PE with IVIg did not confer a significant advantage.

Introduction

Plasma exchange (PE) shortened the duration of disability in Guillain-Barré syndrome in comparison with standard supportive treatment in two large, open, controlled trials.1, 2 In a comparative open trial of intravenous immunoglobulin (IVIg) and PE, the two treatments had similar effects on recovery time.³ IVIg is potentially a safer and more convenient treatment, but it has not been universally accepted as the preferred treatment because of reports of continued disease progression or relapse after IVIg4, 5 and the fact that the IVIg trial (150 patients)³ was smaller than the PE trials (242¹ and 220²). Although PE (and probably IVIg) shortens the average duration of disease, about 20% of patients are left with substantial disability after either treatment. 1, 2, 3 The mechanisms by which IVIg has a beneficial effect may include anti-idiotypic suppression of autoantibodies.6, 7, 8 After the removal of immunoglobulin and antibodies by PE, rebound synthesis of antibodies to myelin of peripheral nerves may be stimulated.⁹ The administration of IVIg immediately after PE might prevent this rebound synthesis. We have undertaken a multicentre, randomised controlled trial to find out whether IVIg is equivalent to or superior to PE in the treatment of Guillain-Barré syndrome, and whether PE followed by IVIg is superior to the better single treatment.

Section snippets

Patients

Patients with Guillain-Barré syndrome were recruited in 38 centres in 11 countries. Inclusion criteria were: diagnosis by a qualified neurologist; satisfaction of accepted clinical and cerebrospinal-fluid diagnostic criteria;¹ severe disease (requiring aid to walk or worse); age over 16 years; and onset of neuropathic symptoms within the previous 14 days. We excluded patients with atypical forms of Guillain-Barré syndrome, serious pre-existing other disease, or contraindications to PE or IVIg.

Randomisation

Between Jan 30, 1993, and April 30, 1995, 383 patients were enrolled and assigned randomised treatment. During the same period, 268 patients were seen at the trial centres but not entered into randomisation (figure 1). The commonest reasons for non-randomisation were disease severity less than grade 3 (70 patients), onset to diagnosis/referral delay more than 14 days (58), other active medical disorders (35), and atypical forms of Guillain-Barré syndrome, such as Miller Fisher syndrome (27).

Discussion

This trial showed that IVIg is equivalent to PE in reducing the amount of disability at 4 weeks after treatment in Guillain-Barré syndrome. This conclusion is strengthened by the absence of significant differences in any of the secondary outcome measures. Moreover, there was no difference in time to hospital discharge or time to return to work. These findings confirm the conclusion of the first comparative trial of PE and IVIg in Guillain-Barré syndrome.³ The results are also consistent with a

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Guillain- Barré syndrome (GBS) is a neuropathic condition that leads to the rapid development of impairments and is characterized by weakness and numbness or tingling sensation in the legs and arms and sometimes loss of movement and feeling in the legs, arms, upper body, and face. Currently, the cure for the disease is yet to be developed. However, treatment options such as intravenous immunoglobulin (IVIG) and plasma exchange (PE) have been used to minimize the symptoms and duration of the disease. Therefore, this systematic review and meta-analysis compared the efficacy of IVIG and PE in treating GBS patients with severe symptoms.
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Acute/chronic inflammatory polyradiculoneuropathy
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Autoimmune neuropathy may present acutely or with a more progressive and/or relapsing and remitting course. Acute inflammatory neuropathy or Guillain–Barré syndrome (GBS) has variable presentations but by far the most common is acute inflammatory demyelinating polyradiculoneuropathy which is characterized by rapidly progressive proximal and distal symmetric weakness, sensory loss, and depressed reflexes. The most common chronic autoimmune neuropathy is chronic inflammatory demyelinating polyradiculoneuropathy, which in its most typical form is clinically similar to acute inflammatory demyelinating polyradiculoneuropathy (proximal and distal symmetric weakness, sensory loss, and depressed reflexes) but differs in that onset is much more gradual, i.e., over at least 8 weeks. While the majority of GBS cases result from a postinfectious activation of the immune system, presumably in a genetically susceptible host, less is understood regarding the etiopathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy. Both acute and chronic forms of these inflammatory neuropathies are driven by some combination of innate and adaptive immune pathways, with differing contributions depending on the neuropathy subtype. Both disorders are largely clinical diagnoses, but diagnostic tools are available to confirm the diagnosis, prognosticate, detect variant forms, and rule out mimics. Given the autoimmune underpinnings of both disorders, immunosuppressive and immunomodulating treatments are typically given in both diseases; however, they differ in their response to treatment.

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ArticlesRandomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Patients

Randomisation

Discussion

Plasmapheresis and acute Guillain-Barré syndrome

Neurology

Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluids

Ann Neurol

A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome

N Engl J Med

Relapse in Guillain-Barré syndrome after treatment with human immune globulin

Neurology

Human immune globulin infusion in Guillain-Barré syndrome: worsening during and after treatment

Neurology

Immunopathogenesis and treatment of the Guillain-Barré syndrome— part 1

Muscle Nerve

Immunopathogenesis and treatment of the Guillain-Barré syndrome—part 1

Muscle Nerve

The use of intravenous immunoglobulins in the treatment of neuromuscular disorders

Curr Opin Neurol

Articles
Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome