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

  • Review
  • Intervention




Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 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. This review was first published in 2003 and has been most recently updated in 2013.


We aimed to review systematically the evidence from randomised trials of immunomodulatory and immunosuppressive agents other than corticosteroids, immunoglobulin and plasma exchange for CIDP.

Search methods

On 9 July 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register (July 2012), CENTRAL (2012, Issue 6 in The Cochrane Library), MEDLINE (January 1977 to July 2012), EMBASE (January 1980 to July 2012), CINAHL (January 1982 to July 2012) and LILACS (January 1982 to July 2012). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials.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, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as interferon alfa and interferon beta, in participants fulfilling standard diagnostic criteria for CIDP.

Data collection and analysis

Two authors independently selected trials, judged their risk of bias 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). The risk of bias in the two trials of interferon beta-1a for CIDP and the trial of methotrexate was assessed to be low but bias in the trial of azathioprine was judged high. None of these trials showed significant benefit in the primary outcome (measured only in the methotrexate study) or secondary outcomes selected for this review. Severe adverse events occurred no more frequently than in the placebo groups for methotrexate and interferon beta-1a, but participant numbers were low. There was no adverse event reporting in the azathioprine study.

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.



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.


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 realizada por el Centro Cochrane Iberoamericano

Plain language summary

Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for CIDP

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 components. Cochrane systematic reviews have presented evidence that some 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 cytotoxic 'chemotherapy-like' drugs, which kill the harmful immune cells, and drugs that regulate the immune system, such as interferons. High quality evidence that these treatments work is sparse and there have only been four randomised trials that we have been able to identify. One tested the cytotoxic drug azathioprine for nine months involving 27 participants. The second tested 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 randomised trial of interferon beta-1a including 67 participants for 32 weeks. The fourth was a double-blind placebo controlled trial of methotrexate involving 60 participants for 40 weeks. These latter two trials again 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. Not all of the studies reported outcomes that might be considered relevant to drug response or patients. There was no significant bias in the conduct and reporting of the two trials of interferon beta-1a and the trial of methotrexate but there was high risk of bias in the trial of azathioprine. Observational studies of these and other drugs, including the cytotoxic drugs cyclophosphamide, ciclosporin, mycophenolate, rituximab, and alemtuzumab, peripheral blood stem cell transplantation and the immune regulating drug interferon alfa, have been performed but are of insufficient quality to determine whether any of these drugs are beneficial.

Laienverständliche Zusammenfassung

Andere immunmodulatorische Behandlungen als Kortikosteroide, Immunoglobin und Plasmaaustausch bei CIDP

Die chronische entzündliche demyelinisierende Polyneuropathie (CIDP) ist eine seltene Erkrankung, bei der es zu Muskelschwäche und Taubheitsgefühlen der Arme und Beine kommt. Sie kann progressiv oder schubförmig verlaufen. Sie wird wahrscheinlich durch eine Entzündung der Nervenfaserummantelung oder in schweren Fällen der Nervenfasern selbst verursacht. Es wird angenommen, dass eine autoimmune Reaktion bei der Immunzellen gegen Bestandteile der Nervenfaserummantelung fehlgeleitet werden diese Krankheit verursacht. In Reviews von Cochrane wurde Evidenz vorgestellt, die zeigt, dass manche Therapien helfen können. Hierzu gehören Kortikosteroide, Plasmatausch (in der die abnorme Plasmamenge im Blut durch einen Ersatz ausgetauscht wird) und intravenöse Gabe von menschlichem Immunoglobulin (Antikörper). Jedoch ist der Nutzen dieser Behandlungen oft nicht vorhanden, unpassend oder zu kurz, da er nur wenige Wochen andauert. Andere Behandlungsmethoden beinhalten zytotoxische Medikamente (ähnlich einer Chemotherapie), die die schädigenden Immunzellen abtöten, oder Medikamente die das Immunsystem regulieren, wie z.B. Interferone. Qualitativ hochwertige Evidenz zur Wirksamkeit dieser Behandlungen ist selten und nur vier randomisierte, kontrollierte Studien wurden gefunden. Eine testete das zytotoxische Medikament Azathioprine über neun Monate bei 27 Patienten. Eine zweite Studie testete über 12 Wochen das immunregulierende Medikament Interferon Beta-1a an zehn Patienten. Keine der Studien zeigte signifikante Ergebnisse und keine war groß genug um einen moderaten Nutzen zu entdecken. Die dritte Studie war eine doppelt verblindete, randomisierte Studie mit Interferon Beta-1a mit 67 Teilnehmern über 32 Wochen. Die vierte war eine doppelblinde, placebokontrollierte Studie von Methotrexat mit 60 Teilnehmern über 40 Wochen. Die beiden letztgenannten Studien haben auch keinen signifikanten Nutzen von Methotrexat oder Interferon Beta-1a gezeigt. Beide waren nicht groß genug, um einen kleinen oder moderaten Nutzen zu erkennen oder auszuschließen. Nicht alle Studien berichteten Endpunkte, die für das Ansprechen auf das Medikament oder die Patienten relevant sein könnten. Es gab keinen signifikanten Bias in der Durchführung und Berichterstattung der beiden Studien zu Interferon Beta-1a und der Studie zu Methotrexat, aber es gab ein hohes Risiko für Bias in der Studie zu Azathioprin. Beobachtungsstudien über diese und anderen Medikamente, einschließlich der Zytostatika Cyclophosphamid, Cyclosporin, Mycophenolat, Rituximab und Alemtuzumab, Transplantation von Blutstammzellen und des immunregulierenden Medikaments Interferon Alfa, wurden durchgeführt, sind aber von unzureichender Qualität, um festzustellen, ob ein Nutzen von einem der Medikamente ausgeht.

Anmerkungen zur Übersetzung

Koordination durch Cochrane Schweiz

Laički sažetak

Imunomodulacijsko liječenje izuzev kortikosteroida, imunoglobulina i plazmafereze za liječenje kronične upalne demijelinizirajuće poliradikuloneuropatije (CIDP)

Kronična upalna demijelinizirajuća poliradikuloneuropatija (CIDP) je rijetka bolest koja uzrokuje slabost i utrnulost ruku i nogu, koji mogu biti progresivni ili se pojavljivati u obliku razdoblja pogoršanja i smirenja (relapsi i remisije). To se događa zbog upale koja oštećuje izolacijske ovojnice (mijelin) oko pojedinih živčanih vlakana. U teškim slučajevima pogođena su i sama živčana vlakna. Smatra se da je temeljni uzrok autoimuni odgovor organizma u kojem su imune stanice pogrešno usmjerene protiv komponenti mijelina. Drugi Cochrane sustavni pregledi prikupili su dokaze koji potvrđuju da neki postupci liječenja mogu biti korisni za liječenje te bolesti. To su kortikosteroidi, plazmafereza (u kojoj se abnormalni dio plazme iz krvi zamijeni nadomjestkom) i intravenske infuzije ljudskog imunoglobulina (antitijela). Međutim, ti postupci liječenja pacijentima često ne pomažu, nisu prikladni ili učinak traje krtko, odnosno traje samo nekoliko tjedana. Ostale mogućnosti liječenja uključuju citotoksične lijekove kao što je kemoterapija, koji ubijaju štetne imunološke stanice, te lijekove koji reguliraju imunološki sustav, kao što su interferoni. Rijetki su dokazi visoke kvalitete koji potvrđuju učinkovitost tih postupaka liječenja, a provedena su samo četiri randomizirana kontrolirana ispitivanja koja smo uspjeli pronaći u ovom Cochrane sustavnom pregledu. Jedno ispitivanje citotoksičnog lijeka azatioprina tijekom devet mjeseci uključivalo je 27 sudionika. Drugo ispitivanje je analiziralo lijek koji regulira imunološki sustav interferon beta-1a, a uključivalo je 10 sudionika, uz svaki period liječenja u trajanju od 12 tjedana. Niti jedno ispitivanje nije pokazalo značajan rezultat, i niti jedno nije bilo dovoljno veliko kako bi potvrdilo čak i umjerenu korist. Treće ispitivanje je bilo dvostruko slijepo randomizirano kontrolirano ispitivanje interferona beta-1a, koje je uključivalo 67 sudionika tijekom 32 tjedna. Četvrto je ispitivanje bilo dvostruko slijepo placebo kontrolirano ispitivanje metotreksata koje je uključivalo 60 sudionika tijekom 40 tjedana. Te dvije studije ponovo nisu pokazale značajnu korist od metotreksata ili interferona beta-1a, a također nisu bile dovoljno velike da otkriju ili isključe manju ili umjerenu korist. U tim znanstvenim radovima nisu opisani svi rezultati dobiveni iz studija koji bi se mogli smatrati relevantnim za odgovor lijeka ili za pacijente. Nije bilo značajne pristranosti u vođenju i prikazivanju podataka u studijama o interferonu beta-1a i ispitivanju metotreksata, ali je uočen veliki rizik od pristranosti u ispitivanju azatioprina. Opservacijska ispitivanja ovih i drugi lijekovi, uključujući citotoksične lijekove ciklofosfamid, ciklosporin, mikofenolat, rituksimab i alemtuzumab, transplantacija matičnih stanica periferne krvi, te lijek za regulaciju imunološkog sustava - interferon alfa, provedena su, ali su nedovoljne kvalitete kako bi potvrdila da je bilo koja od ovih terapija korisna.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Jasna Safić
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