Chronic Inflammatory Demyelinating Polyneuropathy
The second trial had a cross-over design and compared six weeks oral prednisolone starting with 60mg daily and tapering to 10mg with a single course of IVIg at 2.0g/kg.27
Sixty-two per cent
of prednisolone-treated patients had improved disability scores. There was no significant difference in the proportion of responders in the two treatment groups. The third, double-blind study compared pulsed high dose dexamethasone with standard prednisolone for 32 weeks.28
Forty per cent of patients in both treatment arms achieved and remained in remission at 12 months and both treatments were generally well tolerated. Dexamethasone had a faster onset of action than prednisolone. Surprisingly, 38% of patients deteriorated after start of corticosteroid therapy and this was more frequent in prednisolone- treated patients that in those treated with dexamethasone.
In open-label studies, pulsed high-dose corticosteroids not only appeared to be effective, but a considerable number of patients went into a long-term remission and did not need additional treatment.29–31
The serious long-term side effects – such as diabetes, hypertension, cataract, osteoporosis, peptic ulcer disease and aseptic necrosis of the joints – seen with prolonged treatment with corticosteroids are a major concern in patients with CIDP. Pulsed oral and intravenous corticosteroid treatment seems to reduce the incidence of these long-term adverse events.28–32
Intravenous Immunoglobulin
Several uncontrolled studies have suggested short-term beneficial effects with IVIg administration.17,18,33–37
The mode (or modes) by which
IVIg exerts this effect in CIDP is unknown, but several mechanisms have been suggested and are reviewed elsewhere.38–42
Five randomised trials have compared IVIg (2g/kg bodyweight administered over two to five days) treatment with placebo.44–48
The evidence from RCTs showing that IVIg reduces disability in patients with CIDP has been summarised in a Cochrane systematic review.43
A pooled analysis of these five trials showed that a significantly higher proportion of patients treated with IVIg had improved disability scores within six weeks of onset of treatment than patients who received placebo – relative risk (RR) 2.40 (95% confidence interval [CI] 1.72–3.36); number needed to treat (NNT) 3.03 (95% CI 2.33–4.55).
One RCT compared IVIg with plasma exchange in a cross-over design.49
A total of 1.8g/kg bodyweight IVIg was administered over the course of six weeks and the results compared with plasma exchange twice weekly for three weeks followed by once weekly for a further three weeks. There were no significant differences in outcome between the two treatments. A trial comparing IVIg to prednisolone treatment was discussed above.27
While a minority of patients who respond to initial IVIg treatment do not need further treatment, others often need repeated courses of IVIg over a prolonged period of time. To date, only the Immune Globulin Intravenous CIDP Efficacy (ICE) trial has investigated long-term management with IVIg.48
This trial investigated IVIg used for up to 48
weeks. The initial loading dose was replaced by a maintenance dose of 1g/kg every three weeks. After 24 weeks of treatment, 54% of patients
46
improvements in disability scores for patients started on prednisone 120mg every other day, subsequently tapered and stopped at 12 weeks were significantly greater than for patients who received placebo.26
in the IVIg group had a favourable response, whereas only 21% of patients in the placebo group had improved (NNT 3; 95% CI 2.00–5.85). In a 24 week extension phase, most patients were re-randomised to IVIg or placebo. The majority of patients (86%) treated with IVIg had no relapse and remained clinically stable or improved, whereas 52% patients in the placebo group had no relapse (NNT 2.9; 95% CI 1.82–7.13). Approximately 40% of participants who had been treated with IVIg in the first 24 weeks and were re-randomised to placebo remained clinically stable in the extension phase of the study. This finding may indicate that a considerable number of patients treated with IVIg for six months can achieve remission for at least another 24 weeks. In a long-term follow-up study in 84 patients with CIDP who responded to IVIg treatment, remission was reported in most patients.50
Seventy-three patients (87%) needed at least two courses of treatment. Ten per cent of patients needed IVIg for more than 8.7 years. Median time to remission was 2.1 years.
IVIg has an excellent safety profile. In one series, the incidence of headache was reported to be 54%,51
90% but in a large long-term
observational study adverse reactions were reported in 7% of 1,093 patients with autoimmune diseases treated with IVIg;52
of these were mild-to-moderate and transient, however. The most common adverse events were headache, myalgia, fatigue, fever, nausea, rigors, chest discomfort and high blood pressure. Aseptic meningitis, haemolysis and skin reactions were less frequent.53,54 Serious adverse reactions occur in less than 0.5% of patients and include thromboembolic events such as stroke and myocardial infarction due to increased serum viscosity, renal tubule necrosis and anaphylactic reactions.55,56
Plasma Exchange
Several uncontrolled studies have been published that show a beneficial effect from PE in patients with CIDP.57–60
Two double-blind,
randomised, sham-controlled trials have been summarised in a Cochrane systematic review, which concluded that PE provides significant short-term benefit in about two-thirds of patients with CIDP (although rapid deterioration may occur subsequently).59,61,62
Recently,
a small case series reported stable and long-lasting clinical remission in five patients with CIDP receiving long-term PE.63
As described above, PE and IVIg treatments have been shown to be equivalent.49
More recently, protein immunoadsorption has been compared to IVIg in a small pilot study in patients with CIDP.64
The
rationale behind protein immunoadsorption involves the selective removal of immunoglobulins leaving non-specific protein untouched. At two months, four of five patients had a favourable response to immunoadsorption compared with four of eight patients treated with IVIg. Although immunoadsorption appeared to be safe and efficacious in this study, the small number of patients, large drop-out rate, lack of intention-to-treat analysis and the fact that patients in the IVIg arm had more severe disease severely limits the interpretation of the results.
Adverse events – such as paraesthesia, mild hypotension, urticaria and mild nausea – occur in approximately 4% of PE treatments. Severe side effects – such as severe hypotension, arrhythmia, dyspnoea and severe nausea necessitating interruption or termination of treatment – occur in approximately 1%.
EUROPEAN NEUROLOGICAL REVIEW
There is a requirement for PE to be administered by trained staff in a hospital setting. Difficulties with venous access occur in approximately 1% of patients.65,66
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