Immunomodulatory treatment other than corticosteroids, immunoglobulin and plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy
Abstract
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 We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials.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.
PICOs
Plain language summary
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.
