SCIG Therapy Research Articles

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.

Subcutaneous immunoglobulin dose titration to clinical response in inflammatory neuropathy.

Individualized dosing is an established approach in intravenous immunoglobulin (IVIg) treatment for inflammatory neuropathies. There is less experience in effective dosing strategies for subcutaneous (SC) immunoglobulin. We conducted a retrospective cohort study of patients with inflammatory neuropathies transferring from IVIg to SCIg in two UK peripheral nerve services. I-RODS and grip strength were used to measure outcome. Dose and clinical progress were documented at 1year and at last review. 44/56 patients remained on maintenance SCIg beyond 1year (mean 3.3years, range 1-9years) with stable clinical outcomes. Clinical deteriorations were corrected by small increases in SCIg dose in 20 patients at 1year, a further 9 requiring subsequent further up-titrations. Sixteen tolerated dose reduction. Mean dose change was + 2.4% from baseline. Two patients required IVIg bolus rescue (2g/kg). Three patients successfully discontinued Ig therapy. Nine patients returned to IVIg due to clinical relapse or patient preference. Overall tolerance was good. Dose titration to clinical response is an effective approach in SCIg maintenance therapy.

Intravenous versus Subcutaneous Immunoglobulin in Primary Immunodeficiency: Real-World Evaluation of Safety, Efficacy, and Patient Perceptions

Background: Patients with primary immunodeficiency disorders (PIDD) typically require life-long immunoglobulin (IG) replacement therapy. There are two routes of IG administration: intravenous (IVIG) and subcutaneous (SCIG). To better understand routes of IG administration in the real-world, use in a home infusion setting was evaluated. Objective: To evaluate the safety, efficacy, and perceived responses in PIDD patients on IVIG versus SCIG in a realworld, home infusion setting. Methods: Retrospective data were collected from 2010 to 2018 from a national home infusion pharmacy of PIDD patients receiving IVIG or SCIG therapy for at least 6 months with evaluations for safety, efficacy, and patient perception of response. Results: A total of 149 patients were identified for analysis: IVIG (n=84) and SCIG (n=65). Overall, patients in the SCIG group had higher rates of local adverse reactions, while patients receiving IVIG had higher rates of systemic adverse reactions. Both SCIG and IVIG were effective as the majority of patients had ≤ 1 infection or hospital visit within the study period. However, patients in the SCIG group had fewer hospital visits and lower rates of infections overall. Patients receiving SCIG also perceived a faster speed of response. Conclusion: SCIG infusions are safe, efficacious, and well tolerated when compared to IVIG, providing PIDD patients with an alternative route of IG administration. Notably, hospital visits and infection rates were significantly reduced in patients receiving SCIG. The overall findings of this study contribute to growing evidence that demonstrates the benefits of SCIG in adult and pediatric patients with PIDD.

Intravenous versus Subcutaneous Immunoglobulin in Primary Immunodeficiency: Real-World Evaluation of Safety, Efficacy, and Patient Perceptions

Background: Patients with primary immunodeficiency disorders (PIDD) typically require life-long immunoglobulin (IG) replacement therapy. There are two routes of IG administration: intravenous (IVIG) and subcutaneous (SCIG). To better understand routes of IG administration in the real-world, use in a home infusion setting was evaluated. Objective: To evaluate the safety, efficacy, and perceived responses in PIDD patients on IVIG versus SCIG in a realworld, home infusion setting. Methods: Retrospective data were collected from 2010 to 2018 from a national home infusion pharmacy of PIDD patients receiving IVIG or SCIG therapy for at least 6 months with evaluations for safety, efficacy, and patient perception of response. Results: A total of 149 patients were identified for analysis: IVIG (n=84) and SCIG (n=65). Overall, patients in the SCIG group had higher rates of local adverse reactions, while patients receiving IVIG had higher rates of systemic adverse reactions. Both SCIG and IVIG were effective as the majority of patients had ≤ 1 infection or hospital visit within the study period. However, patients in the SCIG group had fewer hospital visits and lower rates of infections overall. Patients receiving SCIG also perceived a faster speed of response. Conclusion: SCIG infusions are safe, efficacious, and well tolerated when compared to IVIG, providing PIDD patients with an alternative route of IG administration. Notably, hospital visits and infection rates were significantly reduced in patients receiving SCIG. The overall findings of this study contribute to growing evidence that demonstrates the benefits of SCIG in adult and pediatric patients with PIDD.

Feasibility of switching from intravenous to subcutaneous immunoglobulin in CIDP: PATH trial and clinical experience

The PATH study showed efficacy of subcutaneous IgG administration (SCIG) in chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated the feasibility of switching from intravenous IgG (IVIG) to SCIG in CIDP patients according to PATH data and clinical experience. In PATH, CIDP patients were randomized to SCIG (0.2 or 0.4 g/kg/week) or placebo after IVIG restabilization. Observational studies of switching from IVIG to SCIG in CIDP and multifocal motor neuropathy are also considered. Forty-eight% of PATH subjects experienced ⩾ 1 adverse event (AE) with IVIG (rate: 0.175/infusion). Corresponding percentages for SCIG-0.2 and SCIG-0.4 were 58% and 52% (0.08 and 0.05/infusion). The most common AE was headache for IVIG (16%), and local infusion site reactions for SCIG (19% and 29%). Most subjects (88%) felt SCIG was easier to use versus IVIG. More subjects (p In observational studies, switching from IVIG to SCIG (1–5 infusion[s]/week) was associated with reduced incidence of AEs (22% vs. 1%, and 60% vs. 0%, IVIG vs. SCIG), improved QoL and higher patient preference for SCIG versus IVIG (69–90%). The PATH trial and observational studies document the feasibility, safety and efficacy of SCIG therapy in CIDP.

What Is the Burden of Immunoglobulin Replacement Therapy in Adult Patients With Primary Immunodeficiencies? A Systematic Review.

Primary immunodeficiency disorders (PIDs) are a group of heterogeneous rare disorders, whereby the immune system is missing or not functioning adequately. For patients requiring treatment, the most common option is immunoglobulin replacement therapy (Ig). Treatment of PIDs is simultaneously associated with both improvements in health-related quality of life (HRQoL) and increased treatment burden. This review sought to review studies investigating the burden of Ig treatment, synthesize evidence in relation to administration routes (subcutaneous or intravenous) and instruments used, as well as make recommendations for clinical and research applications in this area for patients aged 16 years and older. We searched Medline, EMBASE, and The Cochrane Library. Sifting of titles was performed by two reviewers, and the assessment of full-text articles by three. From a database which contained 3,770 unique results, 67 full texts were reviewed. Eventually, 17 studies were found to meet the inclusion criteria, and included in this review. Due to data heterogeneity, a narrative, descriptive synthesis of the evidence was undertaken. Most studies were carried out in the USA/North America, used a prospective observational design and involved patients with common variable immune deficiency. Four studies measured the burden of receiving IVIg therapy and 13 measured SCIg therapy. A wide range of measures, primarily designed to measure aspects of treatment satisfaction (e.g., life quality index or a slightly modified version) and HRQoL (e.g., The Short Form-36) had been used. Lack of a parallel control group in most studies meant that changes in outcomes could be due to factors other than changes in the treatment regimen. However, overall, PID patients appeared to report little Ig treatment burden and were satisfied with either modality. However, patient preference appeared to be the delivery of the Ig treatment in the patient's home and SCIg was preferred after switching from IVIg therapy. Individual differences appeared to affect treatment preference and therefore understanding the decision support needs of PID patients facing IG treatment choices would be valuable. Using a questionnaire specifically designed to measure the burden of Ig treatment from the patient's perspective is recommended in future research.

Home-based subcutaneous immunoglobulin therapy vs hospital-based intravenous immunoglobulin therapy: A prospective economic analysis

BackgroundHome-based subcutaneous immunoglobulin (SCIg) administration used for immunoglobulin replacement therapy for patients with primary immunodeficiency has been demonstrated to have benefits compared with hospital-based intravenous immunoglobulin (IVIg) therapy. ObjectiveTo estimate the cost savings associated with treating eligible patients with primary immunodeficiency with home-based SCIg compared with hospital-based IVIg in a prospective study. MethodsThis study was a 12-month prospective observational study that collected information from patient charts, directly from the nurse for time spent with patients and materials used, and directly from the physicians for billing. Data were collected on case report forms at each follow-up. Data were entered in a web-based REDCap database and statistical comparisons were performed. ResultsThe average hospital (including hospital personnel such as nurses) and physician costs were significantly lower in the SCIg group ($1,836 and $84, respectively) than in the IVIg group ($4,187 and $744, respectively), which supported the findings in the number of hospital and physician visits in each group. The total cost was reported from the hospital's (only hospital-related costs) and the health system's (hospital- and physician-related costs) perspectives. For the 2 perspectives, the SCIg group reported significantly lower average total costs than the IVIg group. ConclusionThis is the first prospective analysis of the cost savings associated with home-based SCIG therapy compared with hospital-based IVIG therapy. These findings could help justify provision of home-based therapy training to suitable patients to lower health care costs or improve the capacity of care.

Estimating the Cost of Immunoglobulin Replacement Therapy in Primary Immunodeficiency Patients

Background: Immunoglobulin (Ig) replacement therapy is used for treating a variety of primary immunodeficiency diseases (PIDs). Ig replacement therapy is the most important therapy for these diseases, since it protects the body against infections and reduces autoimmune disease symptoms. The purpose of this research was to estimate the cost of subcutaneous and intravenous Ig therapy in Iran. Methods: This study is carried out from the perspective of Iran’s healthcare system and all the medical costs are calculated. Cost variables include personnel, equipment, and supplies. The data required for cost estimation are obtained from the records of children’s Medical center of Tehran for 2015. Personnel and medical treatment costs are calculated based on relative value units. For SCIg, cost items are extracted from the literature. Results: The total cost of IVIg and SCIg for the health system in the first year of treatment is $1370 and $121 respectively. The results indicate that SCIg reduces costs and is the preferred treatment for PID patients. Conclusions: SCIg therapy significantly reduces the costs of the healthcare system compared to IVIg therapy, and this is enough economic justification for introduction of this treatment in the Iranian healthcare system. SCIg is also critical in reducing the direct costs of patients.

A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis

ABSTRACTSubcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.

New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin

Common variable immune deficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults. The standard of care is intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (scIG) therapy. The cause of CVID is currently unknown, and there is no universally accepted definition of CVID. This creates problems in determining which patients will benefit from IVIG/scIG treatment. In this paper, we review the difficulties with the commonly used European Society of Immune Deficiencies (ESID) and the Pan American Group for Immune Deficiency (PAGID) definition of CVID. We propose new criteria for the diagnosis of CVID, which are based on recent scientific discoveries. Improved diagnostic precision will assist with treatment decisions including IVIG/scIG replacement. We suggest that asymptomatic patients with mild hypogammaglobulinaemia are termed hypogammaglobulinaemia of uncertain significance (HGUS). These patients require long-term follow-up, as some will evolve into CVID.

A Qualitative Analysis of Health-Related Quality of Life and Treatment Satisfaction Associated with Rapid Push Scig Therapy

A Qualitative Analysis of Health-Related Quality of Life and Treatment Satisfaction Associated with Rapid Push Scig Therapy

Basic and clinical immunology – 3030. Subcutaneous immunoglobulin therapy: An option for patients who have experienced thrombotic complications with intravenous therapy

Methods CVID is one of the 6 FDA-approved uses for IVIG, and is required lifelong in these patients. Systemic adverse reactions occur in approximately 2-6% of infusions , while thrombotic events are very rare. A Therapeutic dilemma arose when our patient had a stroke after an IVIG infusion. After the stroke, our patient’s IgG level fell to 1.17 g/L, resulting in recurrent pneumonia. Cautious doses of IVIG were restarted and the patient remained on warfarin. These were tolerated well for 13 years. With the introduction of higher concentrations of IgG available for subcutaneous administration, we transitioned the patient to SCIG since it offered many advantages. The preparation was tolerated well by the patient, resulted in therapeutic trough levels, and was effective at preventing infection. It is also associated with a lower risk of thrombotic complications including stroke theoretically since this is extremely rare, related to the even physiologic nature of serum IG levels, without marked increases in levels following the administration of the SCIG preparation . Results The patient was cautiously continued on IVIG therapy 7 months after the stroke, with modest doses initially of 20g in 250mL solution q4 weeks (goal trough IgG 5-7 g/L). This dose was effective and tolerated well and it was gradually titrated to higher trough levels 9 years later. With known and theoretical advantages of SCIG therapy, the patient achieved therapeutic trough IG level of 9.5 g/L, and did not have any further thrombotic events or other systemic reactions. The patient continues on q3-4-weekly SCIG infusions that are both safe and effective. This therapy may also offer significant Quality of life (QOL) advantages to the patients and their families.

Improved IgG3 Levels and Reduced Infection Rate in a Woman With CVID Switched from Intravenous to Subcutaneous Immunoglobulin Therapy

To report the interesting case of a patient with common variable immune deficiency disease who demonstrated varied responses to intravenous (IV) and subcutaneous (SC) immunoglobulin (Ig) therapy with regard to both infection frequencies and IgG3 subclass determinations. As part of routine medical care, the author monitored total and IgG subclass levels, along with infection frequencies in a 35-year-old woman, with recurrent sinopulmonary infections diagnosed with common variable immune deficiency disease. During treatment with IVIg, the patient's annual rate of infections decreased, although she experienced severe headaches. After being switched to daily SCIg therapy, the headaches stopped, and her annual infection rate declined further. Her IgG3 levels, which were undetectable during IVIg therapy, increased substantially during SCIg treatment. The reason for the observed correlation between IgG3 level restoration and a decline in infection rate after being switched to SCIg therapy is not entirely clear. At the minimum, it may suggest that IgG3 levels may be a simple and useful surrogate marker to monitor Ig replacement sufficiency in certain patients.

Improved quality of life with home therapy with subcutaneous immunoglobulins for patients with secondary hypogammaglobulinaemia

Background We reported 10 cases where SCIg turned out to be the preferred route of Ig replacement therapy for patients who developed secondary hypogammaglobulinaemia following bone marrow transplantation or chemotherapy treatment for neoplasia. Patients’ age ranged from 2 to 19 years old, 7 patients being below the age of 10. Six out of the 10 patients were transitioned from IVIg to SCIg: 4 patients due to systemic side effects associated to IVIg perfusions and 2 patients due to poor quality of life related to frequent travels to the hospital for IVIg infusion. Four out of the 10 patients were Ig naive patients and were started directly on SCIg. All patients received a weekly dose of 100mg/Kg infused in two different sites assisted by a battery-powered pump. Patients were given a 1:1 dose when transitioned from IVIg to SCIg. A significant increase of the IgG level was noted in all patients. All patients tolerated very well SCIg therapy with no reported systemic adverse reactions. Local infusion sites reactions were the most frequent observed reactions with a frequency similar to the one observed in patients with primary immunodeficiency disorders (PIDD). Lastly, parents reported improvement in quality of life under SCIg therapy; their child had improved social functioning, better resistance against infections and much improved overall health. Conclusion While home-based SCIg administration relative to hospital-based IVIg has been shown to improve PIDD patients’ quality of life, we believe that SCIg has the potential to improve patient’s satisfaction and independence also in patients with secondary hypogammaglobulinemia.

Successful Use of Subcutaneous Immunoglobulin in Chronic Neurology Patients (P07.217)

Objective: To report the use of 20% proline-stabilized subcutaneous immunoglobulin (SCIG; Hizentra®) in 2 patients with myasthenia gravis (MG) and 1 patient with chronic inflammatory demyelinating polyneuropathy (CIDP) for whom intravenous immunoglobulin (IVIG) was poorly tolerated or ineffective. Background Guidelines suggest the use of IVIG for treatment of MG and CIDP. However, some patients experience intolerable adverse events or lack of efficacy with IVIG administration. SCIG therapy is used and tolerated in immunodeficient patients. The high volume used in neurologic disease has previously limited SCIG use. Hizentra is the highest concentration SCIG available (20% IgG), allowing for reduced volumes. Design/Methods: Patient 1 is a 14 year-old boy with CIDP who experienced severe headaches and vomiting for up to 8 days after IVIG treatment (1 g/kg/mo) interfering with daily activities. Patient 2 is a 35 year-old female with MG who experienced intolerable headaches with maintenance IVIG (1 g/kg/mo), resulting in poor compliance. Patient 3 is a 13 year-old girl with MG whose symptoms were not improving after IVIG (0.5 g/kg/mo). Results: Patient 1 is treated with 250 mg/kg/wk Hizentra (25 ml/site/4 sites, 2X/wk) and reports improved strength and ability to participate in daily activities, with no adverse effects. Patient 2 is treated with 250 mg/kg/wk Hizentra (25 ml/site/2 sites, 2X/wk) and reports improved energy and MG symptoms, with no adverse effects. Patient 3 is treated with 125 mg/kg/wk (20 ml/site/3 sites, 1X/wk) and reports improved energy, with no adverse effects. Conclusions: SCIG was well tolerated and improved symptoms and quality of life in neurology patients intolerant or unresponsive to IVIG. More research is needed to further assess efficacy in chronic neurological diseases. SCIG should be considered as an alternative to IVIG in certain patients. Disclosure: Ms. Zampelli has received personal compensation for activities with CSL Behring. Dr. Zacek has received personal compensation for activities with CSL Behring. Ms. Levasseur has received personal compensation for activities with CSL Behring as a consultant.

Abstract withdrawn

Methods This is a retrospective study on a cohort of patients with PID. Annual costs associated with IVg therapy were assessed for each patient for the year prior to commencing home-based subcutaneous SCIg therapy and the year after for the costs associated with the SCIg therapy. Demographic and clinical information were collected from patient’s chart. Economic data were captured from administrative databases, patients, families, and healthcare providers. Paired t-tests and non-parametric Wilcoxon tests were used to assess the difference in costs.

Differences in Clinical Outcome in Patients with Common Variable Immunodeficiency Treated with Ig Replacement Therapy: Results from the ESID Database

S A T U R D A Y 36 Differences in Clinical Outcome in Patients with Common Variable Immunodeficiency Treated with Ig Replacement Therapy: Results from the ESID Database G. Kindle, K.Warnatz, O. Paschenko, D. Kumararatne, S. S. Kilic, V. Thon, T. Witte, M. Helbert, T. W. Kuijpers, A. Exley, N. Mahlaoui, G. Notheis, H. Longhurst, U. Baumann, A. Jones, N. K€ut€ukc€uler, M. Borte, P. Wagstr€om, C. Feighery, A. Szaflarska, H. Ritterbusch, S. Reda, T. Kononova, Z. Panahloo, B. Grimbacher; Centre of Chronic Immunodeficiency (CCI), University Medical Center Freiburg and University of Freiburg, Freiburg, GERMANY, Russian Children’s Clinical Hospital, Moscow, RUSSIAN FEDERATION, Cambridge University Hospital NHS Trust (Addenbrooke’s), Cambridge, UNITED KINGDOM, Uludag University Medical Faculty, Bursa, TURKEY, Masaryk University Medical Faculty, St Anne University Hospital, Brno, CZECH REPUBLIC, Department of Clinical Immunology, Hannover Medical School, Hannover, GERMANY, University of Manchester, Manchester, UNITED KINGDOM, Emma Children’s Hospital, Academic Medical Center (AMC), Amsterdam, NETHERLANDS, Cambridge University Health Partners, Papworth Hospital NHS Foundation Trust, Cambridge, UNITED KINGDOM, CEREDIH: The French PID study group, Unit e d’Immuno-H ematologie & Rhumatologie p ediatriques, Hopital Necker-Enfants Malades, Paris, FRANCE, Dr v. Haunersches Kinderspital, Ludwig Maximilians University, Munich, GERMANY, Barts and the London NHS Trust, London, UNITED KINGDOM, Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, GERMANY, Institute of Child Health/Great Ormond Street Hospital, London, UNITED KINGDOM, Ege University, Faculty of Medicine, Dept of Pediatric Immunology, Bornova, Izmir, TURKEY, Children’s Hospital, Municipal Hospital ’St Georg’, Academic Teaching Hospital of the University of Leipzig, Leipzig, GERMANY, Ryhov County Hospital, Jonkoping, SWEDEN, Department of Immunology,Trinity College Dublin & St. James’ Hospital, Dublin, IRELAND, Department of Clinical Immunology, PolishAmerican Institute of Paediatrics, Medical College, Jagiellonian University, Cracow, POLAND, Department of Pediatric Allergy and Immunology, Children’s Hospital, Faculty of Medicine, Ain Shams University, Cairo, EGYPT, Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, RUSSIAN FEDERATION, Medical Science Department, CSL Behring, Haywards Heath, UNITED KINGDOM, Royal Free Hospital & University College London, London, UNITED KINGDOM. RATIONALE:Themost frequent primary immunodeficiency diagnosis in the ESID Database is common variable immunodeficiency (CVID; n52401). The primary treatment is immunoglobulin (Ig) replacement therapy by intravenous (IV) or subcutaneous (SC) administration. We retrospectively assessed the clinical outcome with Ig therapy in patients with CVID by country and route of administration. METHODS:Datawere provided for patients with CVIDwhowere treated with Ig therapy. Four health parameters were evaluated by country and by route of administration. The number of patients with available data varied from 417 to 645 between the four parameters. RESULTS: There was a highly significant variation between countries in the four outcomes (median occurrence per year, p<0.001). The number of days unable to perform daily duties was highest in Poland (22.5) and Netherlands (7.0), and lowest in the UK (1.1). The number of days in hospital due to the immunodeficiency was highest in Poland (18.3) and Turkey (10.7). The overall number of infections was lowest in Russia and Sweden (both 1.0) and highest in Turkey (6.0). Turkey also had the highest number of serious bacterial infections (2.0). In contrast, the differences observed in these clinical outcomes between IVIg versus SCIg therapy were relatively small. CONCLUSIONS: These results appear to show a wide regional variation, whereas the differences observed between IVand SC administration were relatively small. Further research into the confounding factors such as the socio-economic impact of sick-leave, available treatment options in the respective countries and existing local CVID management protocols, should be conducted.

Long-term therapy with high doses of subcutaneous immunoglobulin in multifocal motor neuropathy

In multifocal motor neuropathy (MMN), high dose of IV immunoglobulin (IVIg) is the only established treatment. Subcutaneous self-infusion with immunoglobulin G (IgG) (SCIG) increases patient autonomy and treatment flexibility, and might be associated with fewer side effects due to lower peak IgG levels. In a recent study of 9 patients with MMN, we reported that SCIG preserves muscle strength for a few months of treatment. Five patients preferred to continue SCIG after the trial and another patient chose to apply SCIG. In this case series study of 6 IVIg-responsive patients with MMN on long-term SCIG maintenance therapy, a dose equivalent to their previous IVIg regimen was given for 2 years. Patients were evaluated before and after 3, 6, 9, 18, and 24 months of initiation of treatment using isokinetic strength examination of affected muscle groups, scores of neuropathy impairment and disability, and recording of side effects. The dosage of SCIG varied between 13 and 51 g per week, corresponding to a volume of 80 to 320 mL infused twice or thrice weekly. No major side events were reported, local skin reactions being mild and transient. The impairment and disability scores remained unchanged. Isokinetic muscle strength was stable with a median (range) 3.7% (-8.8 to 14.5) increase at follow-up. Our study shows that long-term SCIG therapy is an alternative approach to IVIg that is desirable for some patients. This 2-year follow-up study provides Class IV evidence of tolerability and safety in a small (n = 6) case series of patients with MMN preferring SCIG to IVIg.

Rapid Subcutaneous IgG Replacement Therapy is Effective and Safe in Children and Adults with Primary Immunodeficiencies—A Prospective, Multi-National Study

Sixty patients (16 children, 44 adults) participated in the study aiming at evaluating: (i) IgG levels when switching patients from intravenous IgG (IVIG) infusions in hospital to subcutaneous (SCIG) self-infusions at home using the same cumulative monthly dose, (ii) protections against infections, and (iii) safety of a new, ready-to-use 16% IgG preparation. All children and 33 adults had received IVIG therapy for >6 months at enrolment. Ten adults who had been on SCIG therapy for many years served as controls. Mean serum IgG trough levels increased in the pre-IVIG children from 7.8 to 9.2 g/L (non-inferiority: p < 0.001) and in the adults from 8.6 to 8.9 g/L (non-inferiority: p < 0.001). Totally 114 respiratory tract infections occurred, 90% of them mild. One serious bacterial infection (pneumonia) was reported for one adult. The annualized rate of serious infections was 0.04 episodes/patient. In total 2297 infusions were given and 28 (1%) systemic adverse reactions occurred, none of them severe. Local tissue reactions declined over time, this being particularly distinct after 8 to 10 weeks. In conclusion, the SCIG administration route was safe. High IgG levels were easily maintained resulting in a very good protection against infections.