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Review
. 2025 Feb 12;14(4):1203.
doi: 10.3390/jcm14041203.

Real-World Effectiveness, Safety, and Tolerability of Facilitated Subcutaneous Immunoglobulin 10% in Secondary Immunodeficiency Disease: A Systematic Literature Review

Maria Dimou  1 , Angelo Vacca  2 , Silvia Sánchez-Ramón  3 , Ewa Karakulska-Prystupiuk  4 , Vikte Lionikaite  5 , Csaba Siffel  6   7 , Colin Anderson-Smits  6 , Marta Kamieniak  6
Affiliations
Review

Real-World Effectiveness, Safety, and Tolerability of Facilitated Subcutaneous Immunoglobulin 10% in Secondary Immunodeficiency Disease: A Systematic Literature Review

Maria Dimou et al. J Clin Med. .

Abstract

Background: Secondary immunodeficiency disease (SID) is a complex, heterogeneous condition that occurs when extrinsic factors weaken the immune system. Expert consensus guidelines recommend immunoglobulin replacement therapy to manage immunoglobulin G (IgG) levels and mitigate severe, recurrent, and persistent infections. Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% is a dual-vial unit of IgG and recombinant human hyaluronidase; the latter enables absorption of higher volumes of IgG than conventional subcutaneous therapies. Methods: For this systematic literature review, Embase, MEDLINE®, and the Cochrane Library were searched on 9 August 2023, with supplemental congress searches. Results: Eight studies fulfilled the inclusion criteria, reporting real-world evidence of the clinical effectiveness, safety, and tolerability of fSCIG 10% in 183 patients with SID in Europe from September 2014 to August 2021. The potential causes of SID were primarily hematological malignancies, most commonly chronic lymphocytic leukemia. Treatment was typically administered at 4-week or 3-week intervals, with doses of approximately 0.4 g/kg/month. Infections were rare during follow-up, with numerical reductions observed after fSCIG 10% treatment initiation compared with the period before initiation. Adverse reactions, including local infusion site reactions, and tolerability events were uncommon. Conclusions: Given the recency of fSCIG 10% use in patients with SID, there are opportunities for future research to better understand survival and patient-reported outcomes after receiving this treatment. Despite SID heterogeneity, this study demonstrates the feasibility of fSCIG 10% treatment for this condition.

Keywords: hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10%; infection; real-world evidence; safety; secondary immunodeficiency; tolerability.

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Conflict of interest statement

M.D., S.S.-R. and E.K.-P. have no conflicts of interest to disclose. A.V. has received access to scientific resources and protected time for conducting this research from funding granted by the “PIANO NAZIONALE DI RIPRESA E RESILIENZA—PNRR” mission 4—Component C2, “Fondo per il Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale—PRIN” (n.2022ZKKWLW), and from the Ministero della Salute-Progetto “AmICA: Assistenza olistica Intelligente per l’aCtive Ageing in ecosistemi indoor e outdoor”, Traiettoria 1 “Active & Healthy Ageing—Tecnologie per l’invecchiamento attivo e l’assistenza domiciliare”(T1-MZ-09). V.L. is an employee of Oxford PharmaGenesis Ltd., Oxford, UK, which was contracted by Takeda Pharmaceuticals International AG to support the design and conduct of the systematic literature review. C.S. and M.K. are employees of Takeda Development Center Americas, Inc. and are Takeda shareholders. C.A.-S. was an employee of Takeda Development Center Americas, Inc. and a Takeda shareholder at the time of the study, and is now an employee of Gilead Sciences.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. a A full-text research article (Dimou et al., 2023 [33]) replaced the related congress abstract (Dimou et al., 2022 [32]) that was identified during the systematic searches.
Figure 2
Figure 2
Potential causes of SID [31,33,34,35,36,37,38,39,40]. a Borget et al. (2022) listed, but did not quantify, the potential causes as “chronic lymphocytic leukemia, multiple myeloma, or patients pre-and post-allogeneic hematopoietic stem-cell transplantation” [40]. b The FIGARO and SENEQA studies listed these categories as “indications for IgRT”. FIGARO, Facilitated Immunoglobulin Administration Registry And Outcomes; HSCT, hematopoietic stem cell transplantation; IgRT, immunoglobulin replacement therapy; RAHPP; Retrospective chart Analysis of HyQvia usage in Pediatric Patients with PID or SID; SENEQA, Study in the Elderly: Non-interventional retrospective HyQvia Assessment; SID, secondary immunodeficiency disease.
Figure 3
Figure 3
fSCIG 10% doses reported in studies with available data for patients with SID only [31,33,36,39]. FIGARO, Facilitated Immunoglobulin Administration Registry and Outcomes; fSCIG, hyaluronidase-facilitated subcutaneous immunoglobulin; IQR, interquartile range; SID, secondary immunodeficiency disease.
Figure 4
Figure 4
fSCIG 10% infusion rates reported in studies with available data for patients with SID only [33,38]. FIGARO, Facilitated Immunoglobulin Administration Registry and Outcomes; fSCIG, hyaluronidase-facilitated subcutaneous immunoglobulin; IQR, interquartile range; SENEQA, Study in the Elderly: Non-interventional retrospective HyQvia Assessment; SID, secondary immunodeficiency disease.
Figure 5
Figure 5
Serum IgG concentrations reported in studies with available data for patients with SID only [33,36,38,39]. FIGARO, Facilitated Immunoglobulin Administration Registry and Outcomes; fSCIG, hyaluronidase-facilitated subcutaneous immunoglobulin; IgG, immunoglobulin G; IQR, interquartile range; IVIG, intravenous immunoglobulin; SD, standard deviation; SENEQA, Study in the Elderly: Non-interventional retrospective HyQvia Assessment.
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