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

BackgroundImmunoglobulin (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.AimThis 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.ResultsResults 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 consolidatedConclusionsThis 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.

Real-World Experiences With Facilitated Subcutaneous Immunoglobulin Substitution in Patients With Hypogammaglobulinemia, Using a Three-Step Ramp-Up Schedule

Immunoglobulin replacement therapy with facilitated subcutaneous immunoglobulin (fSCIg) can be self-administrated at home and given at longer intervals compared to subcutaneous immunoglobulin (SCIg) therapy, but real-word experience of home-based fSCIg therapy is limited. Herein we present our real-word clinical experiences with home-based fSCIg therapy using a three-step ramp-up schedule. We registered data from all patients with immunodeficiency starting fSCIg from 01.01.2017 to 31.12.2019. For comparison we also included patients starting conventional SCIg training. Fifty-four patients followed for a median of 18 months (IQR 12, range 0–40), received fSCIg training, and 84 patients received conventional SCIg training. Out of 54 patients starting with fSCIg, 41 patients had previous experience with conventional SCIg therapy, and the main reason for starting fSCIg was ‘longer intervals between therapies’ (n=48). We found an increase in training requirement for fSCIg (3 ± 1 [2-9] days) compared to conventional SCIg (2 ± 0 [1-7] days), P< 0.001 (median ± IQR, [range]). For fSCIg training, IgG levels were stable from baseline (8.9 ± 2.3 g/L), 3-6 months (10.2 ± 2.2 g/L) and 9-12 months (9.9 ± 2.3 g/L), P= 0.11 (mean ± SD). The most common side-effect was: ‘rubor around injection site’ (n=48, 89%). No patients experienced severe adverse events (grade 3-4). Thirteen patients (24%) discontinued fSCIg therapy due to local adverse events (n=9), cognitive/psychological difficulties (n=6) and/or systemic adverse events (n=3). In conclusion, fSCIg training using a three-step ramp-up schedule is safe and well tolerated by the majority of patients, but requires longer training time compared to conventional SCIg.

Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg

Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of administration and how they can affect dosing strategies and treatment optimization need to be understood. In general, the efficacy of IVIg and SCIg appear comparable in CIDP, but SCIg may offer some safety and quality of life advantages to some patients. The differences in pharmacokinetic (PK) profile and infusion regimens account for many of the differences between IVIg and SCIg. IVIg is administered as a large bolus every 3–4 weeks resulting in cyclic fluctuations in Ig concentration that have been linked to systemic adverse events (AEs) (potentially caused by high Ig levels) and end of dose “wear-off” effects (potentially caused by low Ig concentration). SCIg is administered as a smaller weekly, or twice weekly, volume resulting in near steady-state Ig levels that have been linked to continuously maintained function and reduced systemic AEs, but an increase in local reactions at the infusion site. The reduced frequency of systemic AEs observed with SCIg is likely related to the avoidance of high Ig concentrations. Some small studies in immune-mediated neuropathies have focused on serum Ig data to evaluate its potential use as a biomarker to aid clinical decision-making. Analyzing dose data may help understand how establishing and monitoring patients' Ig concentration could aid dose optimization and the transition from IVIg to SCIg therapy.

Dose Adjustment of Subcutaneous IgG in Chronic Inflammatory Demyelinating Polyneuropathy

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy that is characterized by a slowly progressive sensory and motor involvement lasting at least 2 months. We present a CIDP patient on subcutaneous Ig (SCIg). Upon fine-tuning his dose from 24 to 28 g/week, this showed a dramatic improvement in both hand grip (13–25%) and dorsiflexion (73–278%). Follow-up nerve conduction studies also demonstrated significant improvements in latencies, motor amplitudes, and conduction velocities. Ongoing surveillance of CIDP patients receiving SCIg therapy is therefore necessary to ensure therapeutic optimization.