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

Research output: Contribution to journalArticle

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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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Caprylates
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Intravenous Immunoglobulins
Chromatography
Randomized Controlled Trials
Placebos
Therapeutics
Hand
Intention to Treat Analysis
Hand Strength
Cross-Over Studies
Headache

ASJC Scopus subject areas

  • Clinical Neurology

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Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study) : a randomised placebo-controlled trial. / Hughes, Richard A C; Donofrio, Peter; Bril, Vera; Dalakas, Marinos C.; Deng, Chunqin; Hanna, Kim; Hartung, Hans Peter; Latov, Norman; Merkies, Ingemar S J; van Doorn, Pieter A.; Apostolski, S.; Basta, I.; Divac, V.; Pavlovic, S.; Trikic, R.; Drory, V.; Artamonov, I.; Groozman, G.; Zielinska, M.; Fryze, W.; Swiatkiewicz, J.; Munch, C.; Reisin, R.; Pardal, A. M.; Marchesoni, C.; Chapman, J.; Benedetti, L.; Ghiglione, E.; Grandis, M.; Narciso, E.; Schenone, A.; Stelmasiak, Z.; Bartosik-Psujek, H.; Belniak, E.; Chyrchel, U.; Kaminski, M.; Banach, M.; Bogucki, A.; Pozdzik-Koseda, A.; Szadkowska, I.; Dubrovsky, A.; Fulgenzi, E.; Lautre, A.; Bednarik, J.; Dacci, P.; del Carro, U.; Fazio, R.; Malaguti, M.; Riva, N.; Thomas, F. P.; Nations, S.; Trivedi, J.; Wolfe, G.; Patwa, H.; Tsao, B.; Cho, S.; Oh, S.; Morgan, M.

In: The Lancet Neurology, Vol. 7, No. 2, 02.2008, p. 136-144.

Research output: Contribution to journalArticle

Hughes, RAC, Donofrio, P, Bril, V, Dalakas, MC, Deng, C, Hanna, K, Hartung, HP, Latov, N, Merkies, ISJ, van Doorn, PA, Apostolski, S, Basta, I, Divac, V, Pavlovic, S, Trikic, R, Drory, V, Artamonov, I, Groozman, G, Zielinska, M, Fryze, W, Swiatkiewicz, J, Munch, C, Reisin, R, Pardal, AM, Marchesoni, C, Chapman, J, Benedetti, L, Ghiglione, E, Grandis, M, Narciso, E, Schenone, A, Stelmasiak, Z, Bartosik-Psujek, H, Belniak, E, Chyrchel, U, Kaminski, M, Banach, M, Bogucki, A, Pozdzik-Koseda, A, Szadkowska, I, Dubrovsky, A, Fulgenzi, E, Lautre, A, Bednarik, J, Dacci, P, del Carro, U, Fazio, R, Malaguti, M, Riva, N, Thomas, FP, Nations, S, Trivedi, J, Wolfe, G, Patwa, H, Tsao, B, Cho, S, Oh, S & 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, vol. 7, no. 2, pp. 136-144. https://doi.org/10.1016/S1474-4422(07)70329-0
Hughes, Richard A C ; Donofrio, Peter ; Bril, Vera ; Dalakas, Marinos C. ; Deng, Chunqin ; Hanna, Kim ; Hartung, Hans Peter ; Latov, Norman ; Merkies, Ingemar S J ; van Doorn, Pieter A. ; Apostolski, S. ; Basta, I. ; Divac, V. ; Pavlovic, S. ; Trikic, R. ; Drory, V. ; Artamonov, I. ; Groozman, G. ; Zielinska, M. ; Fryze, W. ; Swiatkiewicz, J. ; Munch, C. ; Reisin, R. ; Pardal, A. M. ; Marchesoni, C. ; Chapman, J. ; Benedetti, L. ; Ghiglione, E. ; Grandis, M. ; Narciso, E. ; Schenone, A. ; Stelmasiak, Z. ; Bartosik-Psujek, H. ; Belniak, E. ; Chyrchel, U. ; Kaminski, M. ; Banach, M. ; Bogucki, A. ; Pozdzik-Koseda, A. ; Szadkowska, I. ; Dubrovsky, A. ; Fulgenzi, E. ; Lautre, A. ; Bednarik, J. ; Dacci, P. ; del Carro, U. ; Fazio, R. ; Malaguti, M. ; Riva, N. ; Thomas, F. P. ; Nations, S. ; Trivedi, J. ; Wolfe, G. ; Patwa, H. ; Tsao, B. ; Cho, S. ; Oh, S. ; Morgan, M. / Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study) : a randomised placebo-controlled trial. In: The Lancet Neurology. 2008 ; Vol. 7, No. 2. pp. 136-144.
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title = "Intravenous immune globulin (10{\%} caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial",
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.",
author = "Hughes, {Richard A C} and Peter Donofrio and Vera Bril and Dalakas, {Marinos C.} and Chunqin Deng and Kim Hanna and Hartung, {Hans Peter} and Norman Latov and Merkies, {Ingemar S J} and {van Doorn}, {Pieter A.} and S. Apostolski and I. Basta and V. Divac and S. Pavlovic and R. Trikic and V. Drory and I. Artamonov and G. Groozman and M. Zielinska and W. Fryze and J. Swiatkiewicz and C. Munch and R. Reisin and Pardal, {A. M.} and C. Marchesoni and J. Chapman and L. Benedetti and E. Ghiglione and M. Grandis and E. Narciso and A. Schenone and Z. Stelmasiak and H. Bartosik-Psujek and E. Belniak and U. Chyrchel and M. Kaminski and M. Banach and A. Bogucki and A. Pozdzik-Koseda and I. Szadkowska and A. Dubrovsky and E. Fulgenzi and A. Lautre and J. Bednarik and P. Dacci and {del Carro}, U. and R. Fazio and M. Malaguti and N. Riva and Thomas, {F. P.} and S. Nations and J. Trivedi and G. Wolfe and H. Patwa and B. Tsao and S. Cho and S. Oh and M. Morgan",
year = "2008",
month = "2",
doi = "10.1016/S1474-4422(07)70329-0",
language = "English (US)",
volume = "7",
pages = "136--144",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "2",

}

TY - JOUR

T1 - Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study)

T2 - a randomised placebo-controlled trial

AU - Hughes, Richard A C

AU - Donofrio, Peter

AU - Bril, Vera

AU - Dalakas, Marinos C.

AU - Deng, Chunqin

AU - Hanna, Kim

AU - Hartung, Hans Peter

AU - Latov, Norman

AU - Merkies, Ingemar S J

AU - van Doorn, Pieter A.

AU - Apostolski, S.

AU - Basta, I.

AU - Divac, V.

AU - Pavlovic, S.

AU - Trikic, R.

AU - Drory, V.

AU - Artamonov, I.

AU - Groozman, G.

AU - Zielinska, M.

AU - Fryze, W.

AU - Swiatkiewicz, J.

AU - Munch, C.

AU - Reisin, R.

AU - Pardal, A. M.

AU - Marchesoni, C.

AU - Chapman, J.

AU - Benedetti, L.

AU - Ghiglione, E.

AU - Grandis, M.

AU - Narciso, E.

AU - Schenone, A.

AU - Stelmasiak, Z.

AU - Bartosik-Psujek, H.

AU - Belniak, E.

AU - Chyrchel, U.

AU - Kaminski, M.

AU - Banach, M.

AU - Bogucki, A.

AU - Pozdzik-Koseda, A.

AU - Szadkowska, I.

AU - Dubrovsky, A.

AU - Fulgenzi, E.

AU - Lautre, A.

AU - Bednarik, J.

AU - Dacci, P.

AU - del Carro, U.

AU - Fazio, R.

AU - Malaguti, M.

AU - Riva, N.

AU - Thomas, F. P.

AU - Nations, S.

AU - Trivedi, J.

AU - Wolfe, G.

AU - Patwa, H.

AU - Tsao, B.

AU - Cho, S.

AU - Oh, S.

AU - Morgan, M.

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

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