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Intervention Review

Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy

  1. Mohamed Mahdi-Rogers1,*,
  2. Anthony V Swan2,
  3. Pieter A van Doorn3,
  4. Richard AC Hughes4

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 10 NOV 2010

Assessed as up-to-date: 26 MAY 2010

DOI: 10.1002/14651858.CD003280.pub3

How to Cite

Mahdi-Rogers M, Swan AV, van Doorn PA, Hughes RAC. Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database of Systematic Reviews 2010, Issue 11. Art. No.: CD003280. DOI: 10.1002/14651858.CD003280.pub3.

Author Information

  1. 1

    King's College Hospital, Department of Neurology, London, UK

  2. 2

    National Hospital for Neurology and Neurosurgery, Cochrane Neuromuscular Disease Group, MRC Centre for Neuromuscular Disease, London, UK

  3. 3

    Erasmus Medical Centre Rotterdam, Department of Neurology, Rotterdam, Netherlands

  4. 4

    National Hospital for Neurology and Neurosurgery, MRC Centre for Neuromuscular Disease, London, UK

*Mohamed Mahdi-Rogers, Department of Neurology, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. mmahdirogers@hotmail.com.

Publication History

  1. Publication Status: Edited (conclusions changed)
  2. Published Online: 10 NOV 2010

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Background

Chronic inflammatory demyelinating polyradiculoneuropathy is a disease causing progressive or relapsing and remitting weakness and numbness. It is probably due to an autoimmune process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial.

Objectives

We aimed to review systematically the evidence from randomised trials of cytotoxic drugs and interferons other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy.

Search methods

We searched the Cochrane Neuromuscular Disease Group Specialised Register (May 2010), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2), MEDLINE (January 1977 to May 2010), EMBASE (January 1980 to May 2010), CINAHL (January 1982 to May 2010) and LILACS (January 1982 to May 2010). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials.

Selection criteria

We sought randomised and quasi-randomised trials of all immunosuppressive agents such as azathioprine, cyclophosphamide, methotrexate, ciclosporin A, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as interferon alfa and interferon beta in participants fulfilling standard diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy.

Data collection and analysis

Two authors independently selected trials, judged their methodological quality and extracted data. We wanted to measure the change in disability after one year as our primary outcome. Our secondary outcomes were change in disability after four or more weeks (from randomisation), change in impairment after at least one year, change in maximum motor nerve conduction velocity and compound muscle action potential amplitude after one year and for those participants who were receiving corticosteroids or intravenous immunoglobulin, the amount of this medication given during at least one year after randomisation. Participants with one or more serious adverse events during the first year was also a secondary outcome.

Main results

Four trials fulfilled the selection criteria, one of azathioprine (27 participants), two of interferon beta-1a (77 participants in total) and one of methotrexate (60 participants). None of these trials showed significant benefit in the primary outcome or secondary outcomes selected for this review.

Authors' conclusions

The evidence from randomised trials does not show significant benefit from azathioprine, interferon beta-1a or methotrexate but none of the trials was large enough to rule out small or moderate benefit. The evidence from observational studies is insufficient to avoid the need for randomised controlled trials to discover whether these drugs are beneficial. Future trials should have improved designs, more sensitive outcome measures and longer durations.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an uncommon disease that causes weakness and numbness of the arms and legs, which can be progressive or have a relapsing and remitting course. It is due to inflammation which damages the insulating sheaths (myelin) around individual nerve fibres. In severe cases the actual nerve fibres themselves are affected. The underlying cause is thought to be an autoimmune response in which immune cells are misdirected against the myelin. Cochrane reviews have presented evidence that other treatments do help. These are corticosteroids, plasma exchange (in which the abnormal plasma portion of the blood is replaced with a substitute) and intravenous infusions of human immunoglobulin (antibodies). However, benefit from these treatments is often absent, inadequate, or short-lived, lasting only a few weeks. Other treatment options include immunomodulatory or cytotoxic drugs, which kill the harmful immune cells, and drugs that regulate the immune system, such as interferons. There have only been four randomised trials. One was a parallel group open trial of the cytotoxic drug azathioprine for nine months involving 27 participants. The second was a double-blind crossover trial of the immune regulating drug interferon beta-1a involving 10 participants, with each treatment period lasting 12 weeks. Neither trial showed a significant result but neither was large enough to detect even moderate benefit. The third trial was a double-blind dose-ranging trial of interferon beta-1a; 67 participants were randomised and it lasted 32 weeks. The fourth was a double-blind placebo controlled trial of methotrexate involving 60 participants for 40 weeks. These two recent trials, although larger, did not show significant benefit from methotrexate or interferon beta-1a and were still not large enough to detect or rule out minor or moderate benefit. Observational studies of these and other drugs, including the cytotoxic drugs cyclophosphamide, ciclosporin A, and mycophenolate, and the immune regulating drug interferon alfa, have been performed but are insufficient to determine whether any of them are beneficial.

 

Resumen

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. Resumen

Antecedentes

Tratamiento inmunorregulador distinto de los corticosteroides, la inmunoglobulina o el recambio plasmático, para la polirradiculoneuropatía desmielinizante inflamatoria crónica

La polirradiculoneuropatía desmielinizante inflamatoria crónica es una enfermedad que causa debilidad muscular y pérdida de la sensibilidad progresivas o recurrentes y remitentes. Probablemente se deba a un proceso autoinmune. Se esperaría que los fármacos inmunosupresores o inmunomoduladores fueran beneficiosos.

Objetivos

El objetivo fue revisar de manera sistemática las pruebas en ensayos aleatorios de fármacos citotóxicos e interferones, aparte de los corticosteroides, la inmunoglobulina y el recambio plasmático, para la polirradiculoneuropatía desmielinizante inflamatoria crónica.

Estrategia de búsqueda

Se hicieron búsquedas en el registro de ensayos del Grupo Cochrane de Enfermedades Neuromusculares (Cochrane Neuromuscular Disease Group) (mayo 2010), Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) (CENTRAL) (The Cochrane Library, número 2), MEDLINE (enero 1977 hasta mayo 2010), EMBASE (enero 1980 hasta mayo 2010), CINAHL (enero 1982 hasta mayo 2010) y en LILACS (enero 1982 hasta mayo 2010). Se estableció contacto con los autores de los ensayos identificados y a otros especialistas en la enfermedad en busca de otros ensayos publicados y no publicados.

Criterios de selección

Se buscaron ensayos aleatorios y cuasialeatorios de todos los agentes inmunosupresores como azatioprina, ciclofosfamida, metotrexato, ciclosporina A, micofelonato mofetilo y rituximab y de todos los agentes inmunomoduladores, como interferón alfa e interferón beta, en participantes que cumplieran con criterios estándar de diagnóstico para la polirradiculoneuropatía desmielinizante inflamatoria crónica.

Obtención y análisis de los datos

Dos autores, de forma independiente, seleccionaron los ensayos, juzgaron su calidad metodológica y extrajeron los datos. Se deseaba medir los cambios en la discapacidad luego de un año como resultado primario. Nuestros resultados secundarios fueron el cambio en la discapacidad luego de cuatro semanas o más (desde la asignación al azar), el cambio en el deterioro luego de al menos un año, el cambio en la velocidad de conducción máxima de los nervios motores y la amplitud del potencial de acción muscular compuesto luego de un año y, para los participantes que estaban recibiendo corticosteroides o inmunoglobulina intravenosa, la cantidad administrada de dicha medicación durante al menos un año después de la asignación al azar. Otro resultado secundario fueron los participantes con uno o más eventos adversos graves durante el primer año.

Resultados principales

Cuatro ensayos cumplieron con los criterios de selección, uno de la azatioprina (27 participantes), dos del interferón beta1a (77 participantes en total) y uno del metotrexato (60 participantes). Ninguno de estos ensayos demostró beneficios significativos en el resultado primario o los resultados secundarios seleccionados para esta revisión.

Conclusiones de los autores

Las pruebas de los ensayos aleatorios no muestran beneficios significativos de la azatioprina, el interferón beta1a o el metotrexato aunque ninguno de los ensayos fue suficientemente amplio como para descartar un beneficio pequeño o moderado. Las pruebas de los estudios observacionales son insuficientes para evitar la necesidad de ensayos controlados aleatorios para descubrir si estos fármacos son beneficiosos. Los ensayos futuros deben tener diseños mejorados, medidas de resultado más sensibles y duraciones más largas.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano