Abstract
Background
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.
Objectives
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 inThe 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 We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials.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.
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.
