Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

Richard A C Hughes, Peter Donofrio, Vera Bril, Marinos C. Dalakas, Chunqin Deng, Kim Hanna, Hans Peter Hartung, Norman Latov, Ingemar S J Merkies, Pieter A. van Doorn, S. Apostolski, I. Basta, V. Divac, S. Pavlovic, R. Trikic, V. Drory, I. Artamonov, G. Groozman, M. Zielinska, W. FryzeJ. Swiatkiewicz, C. Munch, R. Reisin, A. M. Pardal, C. Marchesoni, J. Chapman, L. Benedetti, E. Ghiglione, M. Grandis, E. Narciso, A. Schenone, Z. Stelmasiak, H. Bartosik-Psujek, E. Belniak, U. Chyrchel, M. Kaminski, M. Banach, A. Bogucki, A. Pozdzik-Koseda, I. Szadkowska, A. Dubrovsky, E. Fulgenzi, A. Lautre, J. Bednarik, P. Dacci, U. del Carro, R. Fazio, M. Malaguti, N. Riva, F. P. Thomas, S. Nations, J. Trivedi, G. Wolfe, H. Patwa, B. Tsao, S. Cho, S. Oh, M. Morgan

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Abstract

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. Findings: 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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
JournalThe Lancet Neurology
Volume7
Issue number2
DOIs
StatePublished - Feb 2008

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Hughes, R. A. C., Donofrio, P., Bril, V., Dalakas, M. C., Deng, C., Hanna, K., Hartung, H. P., Latov, N., Merkies, I. S. J., van Doorn, P. A., Apostolski, S., Basta, I., Divac, V., Pavlovic, S., Trikic, R., Drory, V., Artamonov, I., Groozman, G., Zielinska, M., ... Morgan, M. (2008). Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. The Lancet Neurology, 7(2), 136-144. https://doi.org/10.1016/S1474-4422(07)70329-0