Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial

PATH study group, PATH study group

Research output: Contribution to journalArticle

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Abstract

Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50–74]) patients on placebo, 22 (39% [27–52]) on low-dose SCIg, and 19 (33% [22–46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25% (95% CI 6–41) for low-dose versus placebo (p=0·007), 30% (12–46) for high-dose versus placebo (p=0·001), and 6% (−11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. Funding CSL Behring.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalThe Lancet Neurology
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2018

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Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Immunoglobulins
Placebos
Therapeutics
Intravenous Immunoglobulins
Recurrence
Japan
Numbers Needed To Treat
Polyneuropathies
Israel
Random Allocation
North America
Caregivers
Albumins
Hypersensitivity

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH) : a randomised, double-blind, placebo-controlled, phase 3 trial. / PATH study group; PATH study group.

In: The Lancet Neurology, Vol. 17, No. 1, 01.01.2018, p. 35-46.

Research output: Contribution to journalArticle

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abstract = "Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20{\%} SCIg solution (IgPro20) weekly versus placebo (2{\%} human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33{\%}) to the placebo group, 57 (33{\%}) to the low-dose group, and 58 (34{\%}) to the high-dose group. In the intention-to-treat set, 36 (63{\%} [95{\%} CI 50–74]) patients on placebo, 22 (39{\%} [27–52]) on low-dose SCIg, and 19 (33{\%} [22–46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25{\%} (95{\%} CI 6–41) for low-dose versus placebo (p=0·007), 30{\%} (12–46) for high-dose versus placebo (p=0·001), and 6{\%} (−11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27{\%}) patients (ten [18{\%}] in the placebo group, 17 [30{\%}] in the low-dose group, and 20 [34{\%}] in the high-dose group). Six (3{\%}) patients had 11 serious adverse events: one (2{\%}) patient in the placebo group, three (5{\%}) in the low-dose group, and two (3{\%}) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. Funding CSL Behring.",
author = "{PATH study group} and {PATH study group} and {van Schaik}, {Ivo N.} and Vera Bril and {van Geloven}, Nan and Hartung, {Hans Peter} and Lewis, {Richard A.} and Gen Sobue and Lawo, {John Philip} and Michaela Praus and Orell Mielke and Durn, {Billie L.} and Cornblath, {David R.} and Merkies, {Ingemar S.J.} and A. Sabet and K. George and L. Roberts and R. Carne and S. Blum and R. Henderson and {Van Damme}, P. and J. Demeestere and S. Larue and C. D'Amour and V. Bril and A. Breiner and P. Kunc and M. Valis and J. Sussova and T. Kalous and R. Talab and M. Bednar and T. Toomsoo and I. Rubanovits and K. Gross-Paju and U. Sorro and M. Saarela and M. Auranen and J. Pouget and S. Attarian and {Le Masson}, G. and A. Wielanek-Bachelet and C. Desnuelle and E. Delmont and P. Clavelou and D. Aufauvre and J. Schmidt and J. Zschuentssch and C. Sommer and D. Kramer and O. Hoffmann and Sharma, {Khema R}",
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TY - JOUR

T1 - Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH)

T2 - a randomised, double-blind, placebo-controlled, phase 3 trial

AU - PATH study group

AU - PATH study group

AU - van Schaik, Ivo N.

AU - Bril, Vera

AU - van Geloven, Nan

AU - Hartung, Hans Peter

AU - Lewis, Richard A.

AU - Sobue, Gen

AU - Lawo, John Philip

AU - Praus, Michaela

AU - Mielke, Orell

AU - Durn, Billie L.

AU - Cornblath, David R.

AU - Merkies, Ingemar S.J.

AU - Sabet, A.

AU - George, K.

AU - Roberts, L.

AU - Carne, R.

AU - Blum, S.

AU - Henderson, R.

AU - Van Damme, P.

AU - Demeestere, J.

AU - Larue, S.

AU - D'Amour, C.

AU - Bril, V.

AU - Breiner, A.

AU - Kunc, P.

AU - Valis, M.

AU - Sussova, J.

AU - Kalous, T.

AU - Talab, R.

AU - Bednar, M.

AU - Toomsoo, T.

AU - Rubanovits, I.

AU - Gross-Paju, K.

AU - Sorro, U.

AU - Saarela, M.

AU - Auranen, M.

AU - Pouget, J.

AU - Attarian, S.

AU - Le Masson, G.

AU - Wielanek-Bachelet, A.

AU - Desnuelle, C.

AU - Delmont, E.

AU - Clavelou, P.

AU - Aufauvre, D.

AU - Schmidt, J.

AU - Zschuentssch, J.

AU - Sommer, C.

AU - Kramer, D.

AU - Hoffmann, O.

AU - Sharma, Khema R

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50–74]) patients on placebo, 22 (39% [27–52]) on low-dose SCIg, and 19 (33% [22–46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25% (95% CI 6–41) for low-dose versus placebo (p=0·007), 30% (12–46) for high-dose versus placebo (p=0·001), and 6% (−11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. Funding CSL Behring.

AB - Background Approximately two-thirds of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) need long-term intravenous immunoglobulin. Subcutaneous immunoglobulin (SCIg) is an alternative option for immunoglobulin delivery, but has not previously been investigated in a large trial of CIDP. The PATH study compared relapse rates in patients given SCIg versus placebo. Methods Between March 12, 2012, and Sept 20, 2016, we studied patients from 69 neuromuscular centres in North America, Europe, Israel, Australia, and Japan. Adults with definite or probable CIDP who responded to intravenous immunoglobulin treatment were eligible. We randomly allocated participants to 0·2 g/kg or 0·4 g/kg of a 20% SCIg solution (IgPro20) weekly versus placebo (2% human albumin solution) for maintenance treatment for 24 weeks. We did randomisation in a 1:1:1 ratio with an interactive voice and web response system with a block size of six, stratified by region (Japan or non-Japan). The primary outcome was the proportion of patients with a CIDP relapse or who were withdrawn for any other reason during 24 weeks of treatment. Patients, caregivers, and study personnel, including those assessing outcomes, were masked to treatment assignment. Analyses were done in the intention-to-treat and per-protocol sets. This trial is registered with ClinicalTrials.gov, number NCT01545076. Findings In this randomised, double-blind, placebo-controlled trial, we randomly allocated 172 patients: 57 (33%) to the placebo group, 57 (33%) to the low-dose group, and 58 (34%) to the high-dose group. In the intention-to-treat set, 36 (63% [95% CI 50–74]) patients on placebo, 22 (39% [27–52]) on low-dose SCIg, and 19 (33% [22–46]) on high-dose SCIg had a relapse or were withdrawn from the study for other reasons (p=0·0007). Absolute risk reductions were 25% (95% CI 6–41) for low-dose versus placebo (p=0·007), 30% (12–46) for high-dose versus placebo (p=0·001), and 6% (−11 to 23) for high-dose versus low-dose (p=0·32). Causally related adverse events occurred in 47 (27%) patients (ten [18%] in the placebo group, 17 [30%] in the low-dose group, and 20 [34%] in the high-dose group). Six (3%) patients had 11 serious adverse events: one (2%) patient in the placebo group, three (5%) in the low-dose group, and two (3%) in the high-dose group; only one (an acute allergic skin reaction in the low-dose group) was assessed to be causally related. Interpretation This study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. Funding CSL Behring.

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UR - http://www.scopus.com/inward/citedby.url?scp=85033221920&partnerID=8YFLogxK

U2 - 10.1016/S1474-4422(17)30378-2

DO - 10.1016/S1474-4422(17)30378-2

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AN - SCOPUS:85033221920

VL - 17

SP - 35

EP - 46

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 1

ER -