Use of immunoglobulin (Ig) in peripheral neuropathies. Impact of Ig on remission rates: comparison of intravenous immunoglobulin and subcutaneous immunoglobulin.

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a progressive or relapsing disease with a worldwide prevalence of up to nine individuals per 100 000 1. Randomized trials suggest that corticosteroids, plasma exchange and intravenous immunoglobulin (IVIg) can temporarily reduce impairment and disability. Although approximately 60–70% of the patients respond to the initial therapy, reports on long-term experience of IVIg use in CIDP are rare. Corticosteroids, plasma exchange and IVIg are first-line treatment options in CIDP; however, a risk of long-term adverse effects is the main disadvantage of corticosteroids. Long-term plasma exchange may be less tolerated, and expense can be a concern with IVIg. Two Phase III clinical trials proved the efficacy of IVIg for long-term treatment in CIDP. The IVIg CIDP Efficacy (ICE) trial was a large study that evaluated for the first time the long-term efficacy of IVIg in 117 patients with CIDP 2. Of the 57 patients who received IVIg and were first-period or cross-over-period responders, as assessed with the adjusted inflammatory neuropathy cause and treatment (INCAT) scale, 31 were reassigned randomly to IVIg and 26 were assigned randomly to placebo. IVIg-treated patients (13%) showed a significantly lower relapse rate compared to placebo-treated patients (45%), meaning that 55% of those who were re-randomized to placebo in the extension trial did not deteriorate in a time-frame of approximately 24 weeks 2. In the Privigen Impact on Mobility and Autonomy (PRIMA) study, IVIg-pretreated and IVIg-naive CIDP patients were enrolled and treated for 21 weeks 3. Approximately 61% of the patients showed a significant improvement according to the INCAT scale. Fifty per cent of patients responded to IVIg within the first 4 weeks and 88% of patients within 10 weeks. Of the 31 screened patients, only one CIDP patient (9%) failed the IVIg dependency test and did not deteriorate in the wash-out phase 3. Recently, a retrospective study aimed to evaluate the long-term outcomes in 86 CIDP patients treated with IVIg 4. Data were collected at four time-points: baseline (prior to the start of IVIg treatment); at short-term visit (approximately 6 weeks after IVIg initiation); at mid-term visit (approximately 24 weeks after IVIg); and at last follow-up visit (more than 48 weeks after initiating IVIg treatment). At the mid-term visit, 31 patients had only one IVIg course throughout the entire observation period. Twenty CIDP patients did not receive IVIg at all. Of these 20 patients, 12 were stable. At the long-term visit, 22 patients (25·6%) showed no signs of deterioration 4. There are limited data available on the long-term treatment of CIDP and multifocal motor neuropathy (MMN) with subcutaneous immunoglobulin (SCIg). In a recent report, two patients with atypical CIDP (multifocal acquired demyelinating sensory and motor neuropathy – MADSAM), were treated with SCIg over a time-period of 46 months 5. The Medical Research Council (MRC) sum score remained stable during the entire time-period. In a randomized Phase II study, 30 CIDP patients were enrolled and randomized to placebo and SCIg 6. The treatment period was 12 weeks, with twice- or thrice-weekly SCIg injections (30–300 ml/week; 4·8–48 g/week). After 12 weeks, significant increases (P > 0·05) in isokinetic muscle strength were observed in SCIg-treated patients (5·5 ± 9·5%) compared to the decline observed in the placebo group (14·4 ± 20·3%) 6. Two small case series investigated the effect of SCIg in MMN 7,8. SCIg proved its effectiveness in MMN in short- 7 and long-term use 8. It should be noted that the initial SCIg dose should be 100% equivalent to the monthly IVIg dose 7. A Phase III study proving the efficacy of SCIg in treating CIDP (PATH-Study) is still ongoing (ClinicalTrials.gov identifier: NCT01545076). More recently, a cost-effectiveness study comparing IVIg and SCIg was performed in Italy. Assuming that approximately 2100 CIDP patients exist in Italy, and 50% of those patients were prescribed SCIg, the estimated cost-saving in their model was approximately €1·4 million for the health-care sector 9. However, it should be noted that the cost of SCIg differs within Europe. In conclusion, both IVIg and SCIg are safe and well tolerated for long-term treatment in CIDP and MMN. The most common side effects are headaches (IVIg) and local skin reactions (SCIg). Although not very common, haemolysis is a severe side effect seen with IVIg that can potentially lead to hospitalization, especially when higher doses are administered (2 g/kg body weight).