Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: Results of the ProCID Study.


Journal

Drug safety
ISSN: 1179-1942
Titre abrégé: Drug Saf
Pays: New Zealand
ID NLM: 9002928

Informations de publication

Date de publication:
09 2023
Historique:
accepted: 05 06 2023
medline: 23 8 2023
pubmed: 28 6 2023
entrez: 28 6 2023
Statut: ppublish

Résumé

The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks. All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64-90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication. Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP. EudraCT 2015-005443-14, NCT02638207.

Sections du résumé

BACKGROUND AND AIMS
The ProCID study evaluated the efficacy and safety of three doses of a 10% liquid intravenous immunoglobulin (IVIg) preparation (panzyga
METHODS
Patients were randomised to receive a 2.0 g/kg induction dose followed by maintenance doses of either 0.5, 1.0 or 2.0 g/kg IVIg every 3 weeks over 24 weeks.
RESULTS
All 142 enrolled patients were included in the safety analyses. In total, 286 treatment-emergent adverse events (TEAEs) were reported in 89 patients, of which 173 (60.5%) were considered treatment-related. Most TEAEs were of mild severity. Eleven serious TEAEs were reported in 6 patients. Two serious TEAEs in one patient (headache and vomiting) were considered related to treatment, which resolved without study discontinuation. No treatment-related thrombotic events, haemolytic transfusion reactions or deaths occurred. One patient discontinued the study due to a TEAE (allergic dermatitis) probably related to IVIg. Headache was the only dose-dependent TEAE, with incidences ranging from 2.9 to 23.7%, the incidence of all other TEAEs was similar across treatment groups. Most TEAEs were associated with the induction dose infusion, and the rate of TEAEs decreased thereafter. The median (IQR) daily IVIg dose was 78 (64-90) g, and 94.4% of patients tolerated the maximal infusion rate of 0.12 ml/kg/min without pre-medication.
INTERPRETATION
Infusions of 10% IVIg at doses up to 2.0 g/kg with high infusion rates were safe and well tolerated in patients with CIDP.
CLINICAL TRIAL NUMBERS
EudraCT 2015-005443-14, NCT02638207.

Identifiants

pubmed: 37378806
doi: 10.1007/s40264-023-01326-z
pii: 10.1007/s40264-023-01326-z
pmc: PMC10442284
doi:

Substances chimiques

Immunoglobulins, Intravenous 0

Banques de données

ClinicalTrials.gov
['NCT02638207']
EudraCT
['2015-005443-14']

Types de publication

Randomized Controlled Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

835-845

Investigateurs

S Kastrev (S)
V Rizova (V)
I Milanov (I)
R Massie (R)
R Taleb (R)
M Bednar (M)
P Ridzon (P)
J Schmidt (J)
J Zschüntzsch (J)
R Csilla (R)
L Vécsei (L)
K Rejdak (K)
M Koszewicz (M)
S Budrewicz (S)
A Docu-Axelerad (A)
A Dulamea (A)
M Marian (M)
A Kadar (A)
L Zecheru-Lapusneanu (L)
V Mikhailov (V)
D Zakharov (D)
N Suponeva (N)
M Piradov (M)
N Smolko (N)
D Smolko (D)

Informations de copyright

© 2023. The Author(s).

Références

Koike H, Katsuno M. Pathophysiology of chronic inflammatory demyelinating polyneuropathy: insights into classification and therapeutic strategy. Neurol Ther. 2020;9:213–27. https://doi.org/10.1007/s40120-020-00190-8 .
doi: 10.1007/s40120-020-00190-8 pubmed: 32410146 pmcid: 7606443
Bunschoten C, Jacobs BC, van den Bergh PYK, Cornblath DR, van Doorn PA. Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol. 2019;18:784–94. https://doi.org/10.1016/S1474-4422(19)30144-9 .
doi: 10.1016/S1474-4422(19)30144-9 pubmed: 31076244
van den Bergh PYK, van Doorn PA, Hadden RDM, Avau B, Vankrunkelsven P, Allen JA, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint Task Force-Second revision. Eur J Neurol. 2021;28:3556–83. https://doi.org/10.1111/ene.14959 .
doi: 10.1111/ene.14959 pubmed: 34327760
Hughes RAC, 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. https://doi.org/10.1016/S1474-4422(07)70329-0 .
doi: 10.1016/S1474-4422(07)70329-0 pubmed: 18178525
Merkies ISJ, van Schaik IN, Léger J-M, Bril V, van Geloven N, Hartung H-P, et al. Efficacy and safety of IVIG in CIDP: combined data of the PRIMA and PATH studies. J Peripher Nerv Syst. 2019;24:48–55. https://doi.org/10.1111/jns.12302 .
doi: 10.1111/jns.12302 pubmed: 30672091 pmcid: 6594229
Léger J-M, de Bleecker JL, Sommer C, Robberecht W, Saarela M, Kamienowski J, et al. Efficacy and safety of Privigen(
doi: 10.1111/jns5.12017 pubmed: 23781960 pmcid: 3910165
Nobile-Orazio E, Pujol S, Kasiborski F, Ouaja R, Della Corte G, Bonek R, et al. An international multicenter efficacy and safety study of IqYmune in initial and maintenance treatment of patients with chronic inflammatory demyelinating polyradiculoneuropathy: PRISM study. J Peripher Nerv Syst. 2020;25:356–65. https://doi.org/10.1111/jns.12408 .
doi: 10.1111/jns.12408 pubmed: 32808406 pmcid: 7754365
Kuwabara S, Mori M, Misawa S, Suzuki M, Nishiyama K, Mutoh T, et al. Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial. J Neurol Neurosurg Psychiatry. 2017;88:832–8. https://doi.org/10.1136/jnnp-2017-316427 .
doi: 10.1136/jnnp-2017-316427 pubmed: 28768822
Belmokhtar C, Lozeron P, Adams D, Franques J, Lacour A, Godet E, et al. Efficacy and safety of Octagam® in patients with chronic inflammatory demyelinating polyneuropathy. Neurol Ther. 2019;8:69–78. https://doi.org/10.1007/s40120-019-0132-5 .
doi: 10.1007/s40120-019-0132-5 pubmed: 30903535 pmcid: 6534624
Cornblath DR, van Doorn PA, Hartung H-P, Merkies ISJ, Katzberg HD, Hinterberger D, Clodi E. Randomized trial of three IVIg doses for treating chronic inflammatory demyelinating polyneuropathy. Brain. 2022;145:887–96. https://doi.org/10.1093/brain/awab422 .
doi: 10.1093/brain/awab422 pubmed: 35038723 pmcid: 9050528
Cornblath DR, Hartung H-P, Katzberg HD, Merkies ISJ, van Doorn PA. A randomised, multi-centre phase III study of 3 different doses of intravenous immunoglobulin 10% in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ProCID trial): Study design and protocol. J Peripher Nerv Syst. 2018;23:108–14. https://doi.org/10.1111/jns.12267 .
doi: 10.1111/jns.12267 pubmed: 29603842 pmcid: 6033152
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. https://doi.org/10.1111/j.1468-1331.2009.02930.x .
doi: 10.1111/j.1468-1331.2009.02930.x pubmed: 20456730
Mersich C, Ahrer K, Buchacher A, Ernegger T, Kohla G, Kannicht C, et al. Biochemical characterization and stability of immune globulin intravenous 10% liquid (Panzyga®). Biologicals. 2017;45:33–8. https://doi.org/10.1016/j.biologicals.2016.10.003 .
doi: 10.1016/j.biologicals.2016.10.003 pubmed: 28341308
Radomski KU, Lattner G, Schmidt T, Römisch J. Pathogen Safety of a New Intravenous Immune Globulin 10% Liquid. BioDrugs. 2017;31:125–34. https://doi.org/10.1007/s40259-017-0212-y .
doi: 10.1007/s40259-017-0212-y pubmed: 28236170 pmcid: 5380692
Borte M, Melamed IR, Pulka G, Pyringer B, Knutsen AP, Ochs HD, et al. Efficacy and safety of human intravenous immunoglobulin 10% (Panzyga®) in Patients with primary immunodeficiency diseases: a two-stage, multicenter, prospective, Open-Label Study. J Clin Immunol. 2017;37:603–12. https://doi.org/10.1007/s10875-017-0424-4 .
doi: 10.1007/s10875-017-0424-4 pubmed: 28755067 pmcid: 5554470
Arbach O, Taumberger AB, Wietek S, Cervinek L, Salama A. Efficacy and safety of a new intravenous immunoglobulin (Panzyga® ) in chronic immune thrombocytopenia. Transfus Med. 2019;29:48–54. https://doi.org/10.1111/tme.12573 .
doi: 10.1111/tme.12573 pubmed: 30687970 pmcid: 6850321
Draak THP, Vanhoutte EK, van Nes SI, Gorson KC, van der Pol WL, Notermans NC, et al. Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness. Neurology. 2014;83:2124–32. https://doi.org/10.1212/WNL.0000000000001044 .
doi: 10.1212/WNL.0000000000001044 pubmed: 25378677
Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol. 2005;29:173–84. https://doi.org/10.1385/CRIAI:29:3:173 .
doi: 10.1385/CRIAI:29:3:173 pubmed: 16391392
Jiang Y, Mendoza M, Sarpong E, Mannan S, Ng E, Katzberg H, et al. Efficacy and safety of high infusion rate IVIG in CIDP. Muscle Nerve. 2020;62:637–41. https://doi.org/10.1002/mus.27044 .
doi: 10.1002/mus.27044 pubmed: 32785949
Guo Y, Tian X, Wang X, Xiao Z. Adverse effects of immunoglobulin therapy. Front Immunol. 2018;9:1299. https://doi.org/10.3389/fimmu.2018.01299 .
doi: 10.3389/fimmu.2018.01299 pubmed: 29951056 pmcid: 6008653
Bichuetti-Silva DC, Furlan FP, Nobre FA, Pereira CTM, Gonçalves TRT, Gouveia-Pereira M, et al. Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions. Int Immunopharmacol. 2014;23:442–6. https://doi.org/10.1016/j.intimp.2014.09.015 .
doi: 10.1016/j.intimp.2014.09.015 pubmed: 25257732
Mignogna MD, Fortuna G, Ruoppo E, Adamo D, Leuci S, Fedele S. Variations in serum hemoglobin, albumin, and electrolytes in patients receiving intravenous immunoglobulin therapy: a real clinical threat? Am J Clin Dermatol. 2007;8:291–9. https://doi.org/10.2165/00128071-200708050-00004 .
doi: 10.2165/00128071-200708050-00004 pubmed: 17902731
Göttfried I, Seeber A, Anegg B, Rieger A, Stingl G, Volc-Platzer B. High dose intravenous immunoglobulin (IVIG) in dermatomyositis: clinical responses and effect on sIL-2R levels. Eur J Dermatol. 2000;10:29–35.
pubmed: 10694294
Jordan SC, Tyan D, Stablein D, McIntosh M, Rose S, Vo A, et al. Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol. 2004;15:3256–62. https://doi.org/10.1097/01.ASN.0000145878.92906.9F .
doi: 10.1097/01.ASN.0000145878.92906.9F pubmed: 15579530
Kapoor M, Reilly MM, Manji H, Lunn MP, Aisling SC. Dramatic clinical response to ultra-high dose IVIg in otherwise treatment resistant inflammatory neuropathies. Int J Neurosci. 2022;132:352–61. https://doi.org/10.1080/00207454.2020.1815733 .
doi: 10.1080/00207454.2020.1815733 pubmed: 32842835
Bonilla FA. Adverse effects of immunoglobulin G therapy: thromboembolism and haemolysis. Clin Exp Immunol. 2014;178:72–4. https://doi.org/10.1111/cei.12518 .
doi: 10.1111/cei.12518 pubmed: 25546769 pmcid: 4285498
Carruthers EC, Choi HK, Sayre EC, Aviña-Zubieta JA. Risk of deep venous thrombosis and pulmonary embolism in individuals with polymyositis and dermatomyositis: a general population-based study. Ann Rheum Dis. 2016;75:110–6. https://doi.org/10.1136/annrheumdis-2014-205800 .
doi: 10.1136/annrheumdis-2014-205800 pubmed: 25193998
Chung W-S, Lin C-L, Sung F-C, Lu C-C, Kao C-H. Increased risk of venous thromboembolism in patients with dermatomyositis/polymyositis: a nationwide cohort study. Thromb Res. 2014;134:622–6. https://doi.org/10.1016/j.thromres.2014.06.021 .
doi: 10.1016/j.thromres.2014.06.021 pubmed: 25034321
Selva-O’Callaghan A, Fernández-Luque A, Martínez-Gómez X, Labirua-Iturburu A, Vilardell-Tarrés M. Venous thromboembolism in patients with dermatomyositis and polymyositis. Clin Exp Rheumatol. 2011;29:846–9.
pubmed: 21962007
Aggarwal R, Charles-Schoeman C, Schessl J, Bata-Csörgő Z, Dimachkie MM, Griger Z, et al. Trial of intravenous immune globulin in dermatomyositis. N Engl J Med. 2022;387:1264–78. https://doi.org/10.1056/NEJMoa2117912 .
doi: 10.1056/NEJMoa2117912 pubmed: 36198179
Kapoor M, Hunt I, Spillane J, Bonnett LJ, Hutton EJ, McFadyen J, et al. IVIg-exposure and thromboembolic event risk: findings from the UK Biobank. J Neurol Neurosurg Psychiatry. 2022;93:876–85. https://doi.org/10.1136/jnnp-2022-328881 .
doi: 10.1136/jnnp-2022-328881 pubmed: 35688633
Neeman E, Liu V, Mishra P, Thai KK, Xu J, Clancy HA, et al. Trends and risk factors for venous thromboembolism among hospitalized medical patients. JAMA Netw Open. 2022;5:e2240373. https://doi.org/10.1001/jamanetworkopen.2022.40373 .
doi: 10.1001/jamanetworkopen.2022.40373 pubmed: 36409498 pmcid: 9679881
Anderson FA, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107:I9-16. https://doi.org/10.1161/01.CIR.0000078469.07362.E6 .
doi: 10.1161/01.CIR.0000078469.07362.E6 pubmed: 12814980
Walgaard C, Jacobs BC, Lingsma HF, Steyerberg EW, van den Berg B, Doets AY, et al. Second intravenous immunoglobulin dose in patients with Guillain–Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2021;20:275–83. https://doi.org/10.1016/S1474-4422(20)30494-4 .
doi: 10.1016/S1474-4422(20)30494-4 pubmed: 33743237
Hodkinson JP. Considerations for dosing immunoglobulin in obese patients. Clin Exp Immunol. 2017;188:353–62. https://doi.org/10.1111/cei.12955 .
doi: 10.1111/cei.12955 pubmed: 28263379 pmcid: 5422718

Auteurs

David R Cornblath (DR)

Department of Neurology, Johns Hopkins University, Baltimore, MD, 21287, USA. dcornbl@jhmi.edu.

Pieter A van Doorn (PA)

Department of Neurology, Erasmus University Medical Center, 3015 CE, Rotterdam, The Netherlands.

Hans-Peter Hartung (HP)

Department of Neurology, Medical Faculty, Heinrich Heine University, 40225, Düsseldorf, Germany.
Brain and Mind Center, University of Sydney, Sydney, NSW, 2050, Australia.
Department of Neurology, Medical University of Vienna, 1090, Vienna, Austria.
Department of Neurology, Palacky University, 771 47, Olomouc, Czech Republic.

Ingemar S J Merkies (ISJ)

Department of Neurology, Maastricht University Medical Center, 6229 HX, Maastricht, The Netherlands.
Curaçao Medical Center, Willemstad, Curaçao.

Hans D Katzberg (HD)

Department of Neurology, University of Toronto, Toronto, M5G 2C4, Canada.

Doris Hinterberger (D)

Octapharma PPG, 1100, Vienna, Austria.

Elisabeth Clodi (E)

Octapharma PPG, 1100, Vienna, Austria.

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