Editorial comment: Chronic inflammatory demyelinating polyneuropathy (CIDP) is thought to effect between 1-7.7 patients per 10%000 of population. If diagnosed within one year of the onset of symptoms up to 80% of patients will respond to standard forms of therapy including corticosteroids, intravenous immunoglobulin and plasma exchange that have been tested in randomized and controlled trials. In a smaller patient population, response to these standard treatments is poor reflecting either delayed treatment or other factors. A common practice in treatment of these non-responding or poorly responding patients would be to add an immunosuppressive drug on an empirical basis. The following article represents a randomized and controlled trial in progress that will test the practice in this group of CIDP patients.

The GBS CIDP Foundation International supports its first treatment trial
Consortiums of 23 European investigators are doing a trial to see whether the cytotoxic drug methotrexate helps people with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The Foundation has made a generous donation to support the trial. The investigators thank the Foundation for making the trial possible.

Why the trial is being done
Methotrexate works by blocking the action of folic acid vitamin in bone marrow cells and so suppresses the immune responses which are thought to cause CIDP. Without treatment the course of CIDP is very variable. It can be mild but can also be very disabling. Proven treatments with corticosteroids, intravenous immunoglobulin and plasma exchange do help but may be unsuccessful in some and inadequate in others. Neurologists often recommend immunosuppressive drugs such as azathioprine, cyclosporin or cyclophosphamide among other agents. None of these treatments have been proved to work. Rheumatologists use methotrexate in preference to other drugs of this type in order to control rheumatoid arthritis. We tried methotrexate in ten patients with CIDP and five felt that they benefited. The benefits were modest and to confirm our hypothesis that methotrexate is helpful we need to do a trial in which patients are assigned to true treatment or dummy placebo (identical appearing but inactive tablets) at random, ice, by chance, like spinning a coin to see if it comes down “heads or tails”. If we do not assign treatment like this, we might unwittingly bias the result because we want the treatment to work so much. Such randomized treatment trials are the only way of finding out whether drugs like this work.

Who will take part?
Patients with CIDP attending the clinics of the participating principal investigators will be invited to be screened for eligibility for participation. They will need to have definite CIDP and no complicating illnesses. They also need to be requiring regular corticosteroids or intravenous immunoglobulin. To assist with recruitment we have advertised the trial through the newsletter of the British Guillain-Barré Support
Group (www.gbs.org.uk) so that potential participants can seek referral for inclusion in the trial if they wish. It will not be possible for patients outside the participating centres to take part because of logistic constraints. The centres are in Belgium, France, Italy, the Netherlands and the UK.

What will happen?
Consenting patients will be randomized to receive oral methotrexate or placebo tablets 7.5 mg weekly for 4 weeks, 10 mg weekly for 4 weeks and then 15 mg weekly for 32 weeks. Both groups will receive folic acid supplements 5 mg twice a week to reduce the risk of side effects from methotrexate. After 16 weeks corticosteroids or IVIg will be reduced, subject to satisfactory progress, at a rate of 20% of the baseline dose every 4 weeks. If a participant thinks that they are worsening, they will be instructed to telephone a named individual at their trial centre to arrange for a review within one week. If the worsening is confirmed by the detection of signs of increased impairment, the assessing neurologist will adjust the dose of corlico steroids or IVIg, usually back to the dose which the participant was taking at the start of the trial. All participants will attend the outpatient clinics of their participating centres at 4 weekly intervals for a neurological examination and blood tests. Blood test results will be supervised by a separate health care professional and will not be revealed to the assessing neurologist. In the unlikely event that the blood tests show abnormalities which require dose adjustment, this health care professional will advise the participant to adjust their dose appropriately without telling the assessing neurologist.

How will we tell if it works?
The primary outcome will be percentage change in weekly dose of corticosteroids or IVIg at the end of the trial compared with the beginning. We will also measure the change in impairment (the signs of CIDP which the neurologist measures) and more importantly the change in disability (the way CIDP affects what patients can do) after 16 weeks to give us a measure of early effects and after 40 weeks, which will be the end of the trial. Our statistician, Tony Swan, has advised that with 62 participants we will have a good chance of detecting a reduction in the dose of corticosteroids or IVIg by one quarter.

What are the risks?
Methotrexate at the low doses being used in this trial is well tolerated but occasionally causes side effects especially mouth ulcers, nausea and vomiting and abnormal liver tests. We will give folic acid supplements to reduce these. More serious side effects do occur but are rare.

When will we know the result?
We intend to complete the trial by the end of 2007 and report the results early in 2008. The results will be reported in a medical journal first and in this newsletter as soon as possible afterwards. In the meantime remember that there are many other drugs being used in CIDP and the fact that this trial is being done should not lead to a change in anyone's treatment until the results are available.