Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial.
BACKGROUND
Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP.


METHODS
117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740.


RESULTS
During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension.


CONCLUSIONS
This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.
Hughes
Richard A C
RA
Department of Clinical Neuroscience, King's College London, Guy's Hospital, London, UK. richard.a.hughes@kcl.ac.uk
Donofrio
Peter
P
Bril
Vera
V
Dalakas
Marinos C
MC
Deng
Chunqin
C
Hanna
Kim
K
Hartung
Hans-Peter
HP
Latov
Norman
N
Merkies
Ingemar S J
IS
van Doorn
Pieter A
PA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002210:Caprylates; D002845:Chromatography; D018592:Cross-Over Studies; D004185:Disability Evaluation; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000302:isolation & purification / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000628:therapy*; D012008:Recurrence; D012107:Research Design; D016896:Treatment Outcome
D002210:Caprylates; D016756:Immunoglobulins, Intravenous