Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Feb 3

PMID 35111165

Authors

Maria Giovanna Danieli

Jacopo Umberto Verga

Cristina Mezzanotte

Irene Terrenato

Silvia Svegliati

Maria Beatrice Bilo

Gianluca Moroncini

Affiliations

Soon will be listed here.

Abstract

Background: Immunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings.

Aim: This study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile.

Results: Results support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidated.

Conclusions: This study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients' quality of life.

Citing Articles

A comprehensive review of dermatomyositis treatments - from rediscovered classics to promising horizons.

Sevim E, Kobrin D, Casal-Dominguez M, Pinal-Fernandez I Expert Rev Clin Immunol. 2023; 20(2):197-209.

PMID: 37842905 PMC: 11611049. DOI: 10.1080/1744666X.2023.2270737.

Plasma proteomic profiling reveals KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.

Zhang P, Li M, Zhang Y, Lian C, Sun J, He Y Clin Rheumatol. 2023; 42(8):2145-2154.

PMID: 37160775 DOI: 10.1007/s10067-023-06624-6.

Severe digital ischemia as an unrecognized manifestation in patients with antisynthetase autoantibodies: Case series and systematic literature review.

Yoshida A, Gono T, Okazaki Y, Shirai Y, Takeno M, Kuwana M J Scleroderma Relat Disord. 2022; 7(3):204-216.

PMID: 36211206 PMC: 9537703. DOI: 10.1177/23971983221090857.

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience.

Danieli M, Mezzanotte C, Verga J, Menghini D, Pedini V, Bilo M Biomedicines. 2022; 10(3).

PMID: 35327437 PMC: 8944947. DOI: 10.3390/biomedicines10030635.

References

Sapir T, Shoenfeld Y . Uncovering the hidden potential of intravenous immunoglobulin as an anticancer therapy. Clin Rev Allergy Immunol. 2006; 29(3):307-10. DOI: 10.1385/CRIAI:29:3:307. View

Gilardin L, Bayry J, Kaveri S . Intravenous immunoglobulin as clinical immune-modulating therapy. CMAJ. 2015; 187(4):257-264. PMC: 4347774. DOI: 10.1503/cmaj.130375. View

Cherin P, Marie I, Michallet M, Pelus E, Dantal J, Crave J . Management of adverse events in the treatment of patients with immunoglobulin therapy: A review of evidence. Autoimmun Rev. 2015; 15(1):71-81. DOI: 10.1016/j.autrev.2015.09.002. View

Danieli M, Gelardi C, Pedini V, Gabrielli A . Potential Anti-Tumor Activity of Intravenous and Subcutaneous Immunoglobulin. Isr Med Assoc J. 2018; 20(12):782-783. View

Farini A, Villa C, Tripodi L, Legato M, Torrente Y . Role of Immunoglobulins in Muscular Dystrophies and Inflammatory Myopathies. Front Immunol. 2021; 12:666879. PMC: 8316973. DOI: 10.3389/fimmu.2021.666879. View

Shemer A, Kivity S, Shoenfeld Y . Clinical indications for intravenous immunoglobulin utilization in a tertiary medical center: a 9-year retrospective study. Transfusion. 2017; 58(2):430-438. DOI: 10.1111/trf.14427. View

Corbi A, Sanchez-Ramon S, Dominguez-Soto A . The potential of intravenous immunoglobulins for cancer therapy: a road that is worth taking?. Immunotherapy. 2016; 8(5):601-12. DOI: 10.2217/imt.16.9. View

Quinti I, Soresina A, Agostini C, Spadaro G, Matucci A, Sfika I . Prospective study on CVID patients with adverse reactions to intravenous or subcutaneous IgG administration. J Clin Immunol. 2008; 28(3):263-7. DOI: 10.1007/s10875-007-9169-9. View

Isenberg D, Allen E, Farewell V, Ehrenstein M, Hanna M, Lundberg I . International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford). 2003; 43(1):49-54. DOI: 10.1093/rheumatology/keg427. View

10.

Cherin P, Belizna C, Cartry O, Lascu-Dubos G, de Jaeger C, Delain J . Long-term subcutaneous immunoglobulin use in inflammatory myopathies: A retrospective review of 19 cases. Autoimmun Rev. 2015; 15(3):281-6. DOI: 10.1016/j.autrev.2015.12.003. View

11.

Berger M . L-proline-stabilized human IgG: Privigen® 10% for intravenous use and Hizentra® 20% for subcutaneous use. Immunotherapy. 2011; 3(2):163-76. DOI: 10.2217/imt.10.108. View

12.

Wasserman R, Melamed I, Nelson Jr R, Knutsen A, Fasano M, Stein M . Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011; 50(6):405-14. DOI: 10.2165/11587030-000000000-00000. View

13.

Danieli M, Gambini S, Pettinari L, Logullo F, Veronesi G, Gabrielli A . Impact of treatment on survival in polymyositis and dermatomyositis. A single-centre long-term follow-up study. Autoimmun Rev. 2014; 13(10):1048-54. DOI: 10.1016/j.autrev.2014.08.023. View

14.

Perez E, Orange J, Bonilla F, Chinen J, Chinn I, Dorsey M . Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017; 139(3S):S1-S46. DOI: 10.1016/j.jaci.2016.09.023. View

15.

Misbah S, Sturzenegger M, Borte M, Shapiro R, Wasserman R, Berger M . Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol. 2009; 158 Suppl 1:51-9. PMC: 2801034. DOI: 10.1111/j.1365-2249.2009.04027.x. View

16.

Canessa C, Iacopelli J, Pecoraro A, Spadaro G, Matucci A, Milito C . Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies. Int J Immunopathol Pharmacol. 2016; 30(1):73-82. PMC: 5806788. DOI: 10.1177/0394632016681577. View

17.

Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B . Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008; 112(2):277-86. DOI: 10.1182/blood-2007-11-124545. View

18.

Sultan S, Allen E, Cooper R, Agarwal S, Kiely P, Oddis C . Interrater reliability and aspects of validity of the myositis damage index. Ann Rheum Dis. 2011; 70(7):1272-6. DOI: 10.1136/ard.2010.142117. View

19.

Vultaggio A, Azzari C, Milito C, Finocchi A, Toppino C, Spadaro G . Subcutaneous immunoglobulin replacement therapy in patients with primary immunodeficiency in routine clinical practice: the VISPO prospective multicenter study. Clin Drug Investig. 2015; 35(3):179-85. PMC: 4335091. DOI: 10.1007/s40261-015-0270-1. View

20.

Lundberg I, de Visser M, Werth V . Classification of myositis. Nat Rev Rheumatol. 2018; 14(5):269-278. DOI: 10.1038/nrrheum.2018.41. View