Chronic Inflammatory Demyelinating Polyradiculoneuropathy – An Overview of Existing Treatment cell transplantation for multiple myeloma.125 The potential for serious


adverse events with this treatment, treatment-related mortality rates of 3–14% and lack of sustained response in some patients, means that this treatment is likely only to be suitable for refractory CIDP patients with sufficiently severe disability.126


Treatment Algorithm


Patients with very mild and stable symptoms and disease which does not (or only slightly) interfere with the activities of daily living may be monitored without treatment (see Figure 1). Treatment should be initiated if symptoms or signs progress or are moderate-to-severe from the onset. For first line treatment a choice has to be made between corticosteroids and IVIg. This choice will depend on possible contraindications for either treatment, local availability, cost and patient preference. Patients with a pure motor CIDP should be treated with IVIg rather than corticosteroids, as several patients have been reported to deteriorate following steroid treatment. In the case of corticosteroids, these authors recommend pulsed high-dose dexamethasone as initial treatment (i.e. 40mg for four days) repeated every month for six months. After this, a ‘wait and see’ policy should be implemented as almost 40% of patients will not require further treatment. At least three cycles of dexamethasone should be given before deciding there is no treatment response. In the event that dexamethasone is insufficiently effective, regular daily prednisolone, IVIg or PE should be tried in preference to other treatments. Depending on the degree of disease activity, an immunosuppressive drug can be added to corticosteroid treatment, as these medications may have a steroid-sparing effect (see Table 1).


The starting dose of IVIg is usually 2g/kg bodyweight given over two to five consecutive days. After the first loading dose of IVIg patients should be observed closely, as some will not need further treatment. Patients responding to the loading dose but who subsequently deteriorate should be treated with maintenance IVIg therapy. Apart from the ICE trial – in which all patients got a maintenance dose of 1g/kg every three weeks – there is no evidence on the interval and dosage needed to achieve a stable condition. The dose and frequency of administration need to be titrated according to individual need and regular attempts should be undertaken to decrease the dose to make sure a patient is still IVIg-dependent. When doing this, the dose should be reduced first, and then the frequency of administration. It is important to avoid deterioration (wearing-off) which may be seen just before the next IVIg course is due. Treatment intervals should be such that this deterioration does not happen. If a patient becomes stable on intermittent IVIg, the dose should be reduced after approximately six months in order to test the continued need for IVIg. If high doses of IVIg are needed to maintain good functional status in a patient, the addition of corticosteroids or an immunosuppressive agent should be considered (see Table 1).


Plasma exchange has no advantages over immunoglobulin treatment, but can be used depending on local availability and may be useful in patients who do not respond to corticosteroids or IVIg.


The most important lesson from the Randomised Trial of Methotrexate in CIDP (RMC), Prednisolone Versus Dexamethasone In CIPD Trial (PREDICT) and ICE studies is that patients often are treated for too long. These observations have important practical implications for the treatment of patients with CIDP and mean that regular attempts should be made to taper and to stop therapy. An


EUROPEAN NEUROLOGICAL REVIEW


Table 1: Treatments in Chronic Inflammatory Demyelinating Polyradiculoneuropathy


First-line Treatment*


Corticosteroids Intravenous


immunoglobin Plasma exchange


Second-line Treatment**


Azathioprine*** Methotrexate***


Mycophenolate mofetil


Cyclophosphamide Cyclosporine A Rituximab Etanarcept Intramuscular interferon beta-1a**** Interferon alpha-2a Alemtuzumab Tacrolimus Subcutaneous immunoglobulin


*Shown to be effective in randomised controlled trials; **Efficacy based on case reports and/or case series; ***Efficacy uncertain because only one randomised controlled trial available, which shows no effect in chronic inflammatory demyelinating polyradiculoneuropathy; ****Proven not to be effective.


estimated 15% of patients fail to respond to any treatment. In these patients, the diagnosis should be reconsidered. Some of them probably will not respond to any therapy because of severe secondary axonal involvement which may be irreversible.127


Prospects for the Future


Several immunosuppressive agents are being used, although none has been proven to be effective in a RCT. A full trial with azathioprine is required and treatment with higher doses of methotrexate in patients with CIDP should also be explored. A trial with MMF in CIDP is currently being designed. Based on the pathophysiological assumption that CIDP is an antibody-mediated disease, a trial with rituximab also should be conducted. Recently, there has been a renewed interest for subcutaneous immunoglobulin infusion (SCIg) as an alternative route of immunoglobulin administration. The advantages of weekly subcutaneous self-infusion are a greater level of independency, lower incidence of systemic adverse events and reduction of treatment costs.128


There are two small case series describing three patients with CIDP maintaining functional status after switching from IV to subcutaneous (SC) immunoglobulin.129,130


SCIg has been shown to be effective in patients with multifocal motor neuropathy.131,132


Current treatments are aimed at modulating the immune response, but as yet there is no clear evidence that these treatments also induce axonal regeneration. As non-responsiveness to treatment seems to be associated with a greater degree of axonal dysfunction, finding therapies aimed at protecting the axon and restoring axonal damage are needed. Complement activation plays a major role in secondary axonal damage and poor regeneration and recovery of damaged axons.133–138


The membrane attack complex – the complement’s final pathway – damages axonal membranes and recruits and activates macrophages. Macrophages produce matrix metalloproteases, and breakdown and penetrate the Schwann cell’s basal lamina. Complement inhibition has been shown to ameliorate the clinical, electrophysiological and morphological symptoms and signs in a mouse model of Miller Fisher syndrome.139,140 role in CIDP,141–143


As complement plays a well designed, proof-of-principle studies in patients with CIDP are warranted. n 49 Third-line Treatment**


Autologous stem cell transplantation


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76