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Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial

Authors: Ivo N. van Schaik, Nan van Geloven, Vera Bril, Hans-Peter Hartung, Richard A. Lewis, Gen Sobue, John-Philip Lawo, Orell Mielke, David R. Cornblath, Ingemar S. J. Merkies, on behalf of the PATH study group

Published in: Trials | Issue 1/2016

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Abstract

Background

Subcutaneous administration of Ig (SCIg) has gained popularity as an alternative route of administration but has never been rigorously examined in chronic inflammatory demyelinating polyneuropathy (CIDP).

Methods/design

The primary objective of the PATH study (Polyneuropathy and Treatment with Hizentra) is to determine the efficacy of two different doses of SCIg IgPro20 (0.2 g/kg bw or 0.4 g/kg bw) in a 24-week maintenance treatment of CIDP in comparison to placebo. The primary efficacy endpoint will be the proportion of patients who show CIDP relapse (1-point deterioration on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score) or are withdrawn within 24 weeks after randomization for any reason. IVIg-dependent adult patients with definite or probable CIDP according to the European Federation of Neurological Societies/Peripheral Nerve Society who fulfil the inclusion and exclusion criteria will be eligible. Based on sample-size calculation and relapse assumptions in the three arms, a sample size of 58 is needed per arm (overall sample size will be 350, of which 174 will be randomized). All eligible patients will progress through three study periods: an IgG dependency period (≤12 weeks) to select those who are Ig dependent; an IVIg restabilization period (10 or 13 weeks), which will be performed using the 10 % IgPro10 product; and an SC treatment period (24 weeks, followed by a 1-week completion visit after last follow-up). Patients showing IVIg restabilization will be randomized to demonstrate the efficacy of SCIg IgPro20 maintenance treatment over placebo. After completing the study, subjects are eligible to enter a long-term, open-label, extension study of 1 year or return to their previous treatment. In case of CIDP relapse during the 24-week SC treatment period, IgPro10 rescue medication will be offered. Safety, tolerability, and patients’ preference of Ig administration route will be examined.

Discussion

The PATH trial, which started in March 2012, is expected to finish at the end of 2016. The results will increase knowledge about the efficacy, safety, and tolerability of SCIg in maintenance management of CIDP patients.

Trial Registration

ClinicalTrials.gov, NCT01545076. Registered on 1 March 2012.
Appendix
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Literature
1.
Mathey EK, Park SB, Hughes RAC, Pollard JDA, Armati PJ, Barnett MH, Taylor BV, et al. Chronic inflammatory demyelinating polyneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry. 2015;86:973–85.
2.
Barohn RJ, Kissel JT, Warmolts JR, Mendell JR. Chronic inflammatory demyelinating polyradiculoneuropathy, clinical characteristics, course, and recommendations for diagnostic criteria. Arch Neurol. 1989;46:878–84.CrossRefPubMed
3.
Köller H, Kieseier BC, Jander S, Hartung HP. Chronic inflammatory demyelinating polyneuropathy. N Engl J Med. 2005;352:1343–56.CrossRefPubMed
4.
Merkies ISJ, Hughes RAC, Donofrio P, Bril V, Dalakas MC, Hanna K, et al. Understanding the consequences of chronic inflammatory demyelinating polyradiculoneuropathy from impairments to activity and participation restrictions and reduced quality of life: the ICE study. J Peripher Nerv Syst. 2010;15:208–15. doi:10.​1111/​j.​1529-8027.​2010.​00274.​x.CrossRefPubMed
5.
6.
Jolles S, Orange JS, Gardulf A, Stein MR, Shapiro R, Borte M, et al. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease. Clin Exp Immunol. 2015;179:146–60. doi:10.​1111/​cei.​12485.CrossRefPubMedPubMedCentral
7.
8.
Berger M. Choices in IgG replacement therapy for primary immune deficiency diseases: subcutaneous IgG vs. intravenous IgG and selecting an optimal dose. Curr Opin Allergy Clin Immunol. 2011;11:532–8.CrossRefPubMed
9.
Gardulf A, Nicolay U, Asensio O, Bernatowska E, Böck A, Costa-Carvalho BT, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114:936–42. http://​dx.​doi.​org/​10.​1016/​j.​jaci.​2004.​06.​053.CrossRefPubMed
10.
Nicolay U, Kiessling P, Berger M, Gupta S, Yel L, Roifman CM, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunodeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26:65–72. doi:10.​1007/​s10875-006-8905-x.CrossRefPubMed
11.
Gardulf A, Andersen V, Bjorkander J, Ericson D, Froland SS, Gustafson R, et al. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet. 1995;345:365–9.CrossRefPubMed
12.
13.
Lazzaro C, Lopiano L, Cocito D. Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis. Neurol Sci. 2014;35:1023–34. doi:10.​1007/​s10072-014-1632-9.CrossRefPubMed
14.
Cocito D, Paolasso I, Peci E, Spagone E, Lopiano L. Improvement of quality of life in patients with chronic inflammatory demyelinating polyneuropathy shifting from 16 to 20 % subcutaneous immunoglobulins. Neurol Sci. 2013;34:2061–2. doi:10.​1007/​s10072-013-1426-5.CrossRefPubMed
15.
Lee DH, Linker RA, Paulus W, Schneider-Gold C, Chan A, Gold R. Subcutaneous immunoglobulin infusion: a new therapeutic option in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve. 2008;37:406–9.CrossRefPubMed
16.
Köller H, Schroeter M, Feischen H, Hartung HP, Kieseier BC. Subcutaneous self-infusions of immunoglobulins as a potential therapeutic regimen in immune-mediated neuropathies. J Neurol. 2006;253:1505–6.CrossRefPubMed
17.
18.
19.
20.
21.
Cocito D, Merola A, Romagnolo A, Peci E, Toscano A, Mazzeo A, et al. Subcutaneous immunoglobulin in CIDP and MMN: a different long-term clinical response? J Neurol Neurosurg Psychiatry. 2015. doi:10.​1136/​jnnp-2014-310280.
22.
Magy L, Ghorab K, Calvo J, Vallat JM. Subcutaneous immunoglobulin as maintenence therapy in intravenous immunoglobulin-responsive CIDP patients: long term response in 16 patients. J Peripher Nerv Syst. 2009;14(supp 2):94.
23.
24.
Markvardsen LH, Debost JC, Harbo T, Sindrup SH, Andersen H, Christiansen I, et al. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2013;20:836–42. doi:10.​1111/​ene.​12080.CrossRefPubMed
25.
Markvardsen LH, Harbo T, Sindrup SH, Christiansen I, Andersen H, Jakobsen J, et al. Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy. Eur J Neurol. 2014;21:1465–70. doi:10.​1111/​ene.​12513.CrossRefPubMed
26.
Van den Bergh PYK, Hadden RDM, Bouche P, Cornblath DR, Hahn A, Illa I, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—First Revision. Eur J Neurol. 2010;17:356–63. doi:10.​1111/​j.​1468-1331.​2009.​02930.​x.CrossRefPubMed
27.
Hughes RA, Bensa S, Willison HJ, Van den Bergh P, Comi G, Illa I, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001;50:195–201.CrossRefPubMed
28.
Van Nes SI, Vanhoutte EK, Van Doorn PA, Hermans MCE, Bakkers M, Kuitwaard K, et al. Rasch-built overall disability scale (r-ods) for immune-mediated peripheral neuropathies. Neurology. 2011;76:337–45.CrossRefPubMed
29.
Merkies ISJ, Schmitz PIM, Samijn JPA, Van der Meché FGA, Toyka KV, Van Doorn PA, et al. Assessing grip strength in healthy individuals and patients with immune-mediated polyneuropathies. Muscle Nerve. 2000;23:1393–401.CrossRefPubMed
30.
Merkies ISJ, Van Nes SI, Hanna K, Hughes RAC, Deng C. Confirming the efficacy of intravenous immunoglobulin in CIDP through minimum clinically important differences: shifting from statistical significance to clinical relevance. J Neurol Neurosurg Psychiatry. 2010;81:1194–9.CrossRefPubMed
31.
Leger J-M, De Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, et al. Efficacy and safety of Privigen® in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospectieve, single-arm, open-label Phase III study (the PRIMA study). J Peripher Nerv Syst. 2013;18:130–40.CrossRefPubMedPubMedCentral
32.
Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, et al. Intravenous immune globulin (10 % caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7:136–44.CrossRefPubMed
33.
Kleyweg RP, Van der Meché FGA, Schmitz PI. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome. Muscle Nerve. 1991;14:1103–9.CrossRefPubMed
34.
Léger JM, Chassande B, Musset L, Meininger V, Bouche P, Baumann N. Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study. Brain. 2001;124:145–53.CrossRefPubMed
35.
McCrone P, Chisholm D, Knapp M, Hughes RA, Comi G, Dalakas MC, et al. Cost-utility analysis of intravenous immunoglobulin and prednisolone for chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol. 2003;10:687–94.CrossRefPubMed
36.
Atkinson M, Sinha A, Hass S, Colman S, Kumar R, Brod M, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12. doi:10.​1186/​1477-7525-2-12.CrossRefPubMedPubMedCentral
37.
38.
39.
40.
41.
Group RT. Randomised controlled trial of methotrexate for chronic inflammatory demyelinating polyradiculoneuropathy (RMC trial): a pilot, multicentre study. Lancet Neurol. 2009;8:158–64.CrossRef
42.
Harbo T, Andersen H, Hess A, Hansen K, Sindrup SH, Jakobsen J. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomised, single-blinded cross-over trial. Eur J Neurol. 2009;16:631–8.CrossRefPubMed
43.
44.
Matsuda M, Hoshi K, Gono T, Morita H, Ikeda S. Cyclosporin A in treatment of refractory patients with chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci. 2004;224:29–35.CrossRefPubMed
45.
Gorson KC, Ropper AH, Clark BD, Dew III RB, Simovic D, Allam G. Treatment of chronic inflammatory demyelinating polyneuropathy with inteferon-α 2a. Neurology. 1998;50:84–7.CrossRefPubMed
46.
Gorson KC, Amato AA, Ropper AH. Efficacy of mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy. Neurology. 2004;63:715–7.CrossRefPubMed
47.
Hadden RDM, Sharrack B, Bensa S, Soudain SE, Hughes RAC. Randomized trial of interferon beta-1a in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology. 1999;53:57.CrossRefPubMed
48.
Thompson N, Choudhary PP, Hughes RAC, Quinlivan RM. A novel trial design to study the effect of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol. 1996;243:280–5.CrossRefPubMed
49.
Merkies ISJ, Schmitz PIM, van der Meche FGA, Samijn JPA, Van Doorn PA. Connecting impairment, disability, and handicap in immune mediated polyneuropathies. J Neurol Neurosurg Psychiatry. 2003;74:99–104.CrossRefPubMedPubMedCentral
50.
51.
52.
53.
Bril V, Katzberg H, Donofrio P, Banach M, Dalakas MC, Deng C, et al. Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV. Muscle Nerve. 2009;39:448–55. doi:10.​1002/​mus.​21236.CrossRefPubMed
54.
Jonckheere AR. A distribution-free k-sample test against ordered alternatives. Biometrika. 1954;41:133–45.CrossRef
Metadata
Title
Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (The PATH Study): study protocol for a randomized controlled trial
Authors
Ivo N. van Schaik
Nan van Geloven
Vera Bril
Hans-Peter Hartung
Richard A. Lewis
Gen Sobue
John-Philip Lawo
Orell Mielke
David R. Cornblath
Ingemar S. J. Merkies
on behalf of the PATH study group
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1466-2

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