Insights into Patient Experiences with Facilitated Subcutaneous Immunoglobulin Therapy in Primary Immune Deficiency: A Prospective Observational Cohort.

BACKGROUND: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC. METHOD: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL). RESULTS: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min-max: 2-40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys. CONCLUSION: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.

Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders.

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.

Robust predictive control strategy of SCIG-based drive system.

This article presents a robust finite control set predictive scheme for a stand-alone squirrel cage induction generator (SCIG) drive. This technique is considered an alternative to the drive system due to the inclusion of system nonlinearities and fast dynamic response. The control objective in the distributed generation environment is to fix the output voltage to follow the stand-alone requirement. The strategy establishes optimized switching instants for cost function minimization for both source and load converter control and diminished cross-coupling amid active and reactive power during transient scenarios. The scheme is designed to achieve the minimal effect caused by the parameter uncertainties. During source and load changes, this work will also address the maintenance of dc-link voltage, machine, and load variables at the set value, supported by machine and load-end converter control to achieve stand-alone load objectives. In addition, the presented scheme is also tested with random variation of speed to check the efficacy of the control configuration. The drive performance is evaluated by simulation using MATLAB/Simulink environment. Comprehensive real-time findings obtained from a scaled laboratory test bench using dSPACE-1104 are provided to verify the feasibility of the predictive solution.

Immunoglobulin replacement therapies in inborn errors of immunity: a review.

Immunoglobulins (Ig) were used as a therapeutic modality for the first time in a patient with X-linked agammaglobulinemia in 1952 by Colonel Ogden Bruton, decades before the molecular mechanisms causing the disease were unraveled. In many autoimmune and inflammatory illnesses, human immunoglobulin has been employed as a significant immunomodulatory and immunosuppressive drug. In patients with inborn errors of immunity (IEI), immunoglobulin remains a cornerstone of management. IEIs are notable causes of recurrent infections and autoimmunity due to inheritable single-gene defects in genes encoding for different components of the immune system. As there is decreased immunoglobulin production in IEIs with antibody defects, immunoglobulin replacement is the mainstay of therapy in these disorders. Although serum immunoglobulin levels may not be low in combined immune defects, immunoglobulin replacement is still necessary in these disorders due to a deficiency of functional antibodies and qualitative defects of immunoglobulins. Commercial immunoglobulin preparations are generated from plasma donated by thousands of donors. Immunoglobulin preparations are usually available in two forms: intravenous and subcutaneous immunoglobulins. In the developed world, both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are available, and SCIg is preferred over IVIg for replacement therapy in patients with IEIs. In developing countries, IVIg remains the mainstay of replacement therapy. The rate of adverse events has significantly reduced over the last few years due to advancements in the production process. In this review article, we discuss different aspects of the use of Ig (indications, dosing, mechanism of action, route, adverse effects) in patients with IEIs.

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

The Experiences of Children with Primary Immunodeficiency Who Receive Immunoglobulin Subcutaneously Instead of Intravenously.

BACKGROUND: Children with primary immunodeficiency disorder have begun receiving subcutaneous immunoglobulin (SCIg) instead of intravenous immunoglobulin (IVIg). So, we aim to explore the experiences of primary immunodeficiency children with regard to receiving SCIg instead of IVIg. METHOD: We adopted a phenomenological approach in 2022 in Turkey using semi-structured interviews. We recruited 15 participants using the purposive sampling method. RESULTS: The main theme was the sweetness and bitterness of living with SCIg. The first subtheme was sweetness (sense of freedom, having a normal life, saving time, ease of use, and feeling better). The second subtheme was bitterness (worries about taking responsibility for injection, impaired body image due to abdominal edema, and minimal tolerable complications). DISCUSSION: The results show these children had more sweet experiences than bitter ones. Being flexible in choosing a method, teaching patients to apply it correctly, and providing enough time to cope are as reasons for this.

Immunomodulatory effects of intravenous and subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: An observational study.

BACKGROUND AND PURPOSE: It is not known whether the route of administration affects the mechanisms of action of therapeutic immunoglobulin in chronic inflammatory demyelinating polyneuropathy (CIDP). The aim of this study, therefore, was to compare the immunomodulatory effects of intravenous (IVIg) and subcutaneous immunoglobulin (SCIg) in patients with CIDP and in IVIg-treated common variable immunodeficiency (CVID) patients. METHODS: Serum and peripheral blood mononuclear cell samples were obtained from 30 CIDP patients receiving IVIg, 10 CIDP patients receiving SCIg, and 15 patients with CVID receiving IVIg. Samples and clinical data were obtained prior to IVIg/SCIg and at 3 days, 7 days, and, in CIDP patients receiving IVIg, 21 days post-administration. Serum cytokines were assessed by Luminex-based multiplex assay and enzyme-linked immunosorbent assay. Immune cells were characterized by flow cytometry. RESULTS: Immune cell profiles of CIDP and CVID patients differed in frequencies of myeloid dendritic cells and cytotoxic natural killer cells. During treatment with IVIg or SCIg in CIDP patients, cellular immunomarkers were largely similar. CIDP patients receiving IVIg had higher macrophage inflammatory protein (MIP)-1α (p = 0.01), interleukin (IL)-4 (p = 0.04), and IL-33 (p = 0.04) levels than SCIg recipients. IVIg treatment more broadly modulated cytokines in CIDP than SCIg treatment. CONCLUSIONS: Our study demonstrates that the modulation of cellular immunomarkers in CIDP is independent of the application route of therapeutic immunoglobulin. Minor differences were observed between CIDP and CVID patients. In contrast, cytokines were differentially modulated by IVIg and SCIg in CIDP.

Effects of Body Mass and Age on the Pharmacokinetics of Subcutaneous or Hyaluronidase-facilitated Subcutaneous Immunoglobulin G in Primary Immunodeficiency Diseases.

PURPOSE: To assess the pharmacokinetics (PK) of subcutaneous immunoglobulin (SCIG) and hyaluronidase-facilitated SCIG (fSCIG) therapy across body mass index (BMI) and age categories in patients with primary immunodeficiency diseases (PIDD) previously treated with intravenous immunoglobulin (IVIG). METHODS: Using our previously published integrated population PK model based on data from eight clinical trials, simulations were conducted to examine the effects of BMI and age on serum immunoglobulin G (IgG) PK after administration of SCIG 0.15 g/kg weekly or fSCIG 0.6 g/kg every 4 weeks in patients switching from stable IVIG. Patients were assumed to have baseline IgG trough concentrations of 7 g/L (hypothetical protective threshold). RESULTS: Mean steady-state serum IgG trough values (Cmin,ss or trough) increased with BMI and age. Mean Cmin,ss was 18% (SCIG) and 16% (fSCIG) higher in the obese than the healthy BMI group. Pediatric patients aged < 18 years had 8-22% (SCIG) and 4-20% (fSCIG) lower mean Cmin,ss values than adults, with the youngest group (2- < 6 years) having the lowest Cmin,ss. All patients across populations maintained Cmin,ss IgG concentrations of ≥ 7 g/L after switching to SCIG or fSCIG. CONCLUSION: Both SCIG and fSCIG successfully maintained trough values at or above the hypothetical protective threshold after switching from stable IVIG, irrespective of BMI or age. Differences in trough values between BMI groups and age groups (≤ 22%) may not warrant SCIG or fSCIG dose adjustments based on BMI or age alone; instead, the dosing paradigm should be guided by prior IVIG dose, individual IgG monitoring, and clinical findings.

Immunoglobulin utilization in Canada: a comparative analysis of provincial guidelines and a scoping review of the literature.

BACKGROUND: Canada has high immunoglobulin (IG) product utilization, raising concerns about appropriate utilization, cost and risk of shortages. Currently, there is no national set of standardized IG guidelines, and considerable variations exist among the existing provincial guidelines. The aims of this study were: (1) to compare the existing Canadian provincial guidelines on the use of IG products to identify their consistencies and differences and (2) to examine the existing research in Canada on IG supply and utilization following the establishment of IG guidelines to understand the scope of research and pinpoint the gaps. METHODS: A comparative analysis accounted for the differences across provincial IG guidelines. We highlighted similarities and differences in recommendations for medical conditions. A scoping review of citations from MEDLINE, PubMed, Scopus and Embase databases was conducted for studies published from January 01, 2014, to April 12, 2023. RESULTS: While provincial guidelines represented a considerable overlap in the medical conditions delineated and relatively uniform dose calculations, numerous differences were observed, including in recommendation categories, provision of pediatric dosing, and divergent recommendations for identical conditions based on patient demographics. The scoping review identified 29 studies that focused on the use of IG in Canada. The themes of the studies included: IVIG utilization and audits, the switch from IVIG to SCIG, patient satisfaction with IVIG and/or SCIG, the economic impact of self-administered SCIG versus clinically administered IVIG therapy, and the efficacy and cost-effectiveness of alternative medications to IG treatment. CONCLUSION: The differences in guidelines across provinces and the factors influencing IVIG/SCIG use, patient satisfaction, and cost savings are highlighted. Future research may focus on clarifying costs and comparative effectiveness, exploring factors influencing guideline adherence, and evaluating the impact of updated guidelines on IG use and patient outcomes.

Real-World Use, Safety, and Patient Experience of 20% Subcutaneous Immunoglobulin for Primary Immunodeficiency Diseases.

INTRODUCTION: The CORE study aimed to provide a detailed understanding of real-world immune globulin subcutaneous (human) 20% solution (Ig20Gly) utilization in patients with primary immunodeficiency diseases (PIDs) in Germany and Switzerland. METHODS: Patients with PIDs receiving a stable dose of any subcutaneous immunoglobulin for ≥ 3 months before enrollment were eligible for this multicenter (n = 5), phase 4, non-interventional, prospective, longitudinal cohort study. Besides baseline demographics and clinical characteristics, Ig20Gly utilization and safety data, and patient-reported outcomes (Life Quality Index/Treatment Satisfaction Questionnaire for Medication) were collected at baseline, 6 and 12 months. Statistical analysis was descriptive. RESULTS: Overall, 36 patients provided data at baseline [69.4% female; mean age: 41.6 years (7-78 years)]. Totals of 23 and 26 patients attended 6- and 12-month visits, respectively; 16 attended all three visits. One patient withdrew consent before 6-month follow-up. Median maximum infusion rates of Ig20Gly at baseline, 6 months, and 12 months were 26.7, 24.5, and 40.0 mL/h, respectively (10-60 mL/h). Infusion and dosing parameters remained consistent across time points: patients used a median of two infusion sites, primarily the abdomen, and all patients used an infusion pump; all but one infused at home and most self-administered Ig20Gly (80.8-83.3%) at once-weekly intervals (69.2-73.9%). During follow-up, 10 adverse events were reported: none were rated serious, while 2 were considered probably related to Ig20Gly. Total patient-reported outcome scores remained high throughout the study. CONCLUSION: The CORE study provides real-world evidence of the flexibility, feasibility, safety, and tolerability of Ig20Gly infusions, at mostly weekly intervals, over 1 year in patients with PIDs. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00014562. Registered April 9, 2018, https://drks.de/search/en/trial/DRKS00014562.

Primary immunodeficiency diseases are rare diseases that make patients more likely to develop infections than the general population. Many patients with primary immunodeficiency diseases do not produce enough antibodies, which are an important part of the immune system that fight infection. Replacing antibodies is the main way to treat primary immunodeficiency diseases and reduce the risk of infection. Ig20Gly is a type of medication used to replace antibodies and treat primary immunodeficiency diseases. Patients receive Ig20Gly through a needle inserted under the skin and can learn to do this themselves at home. Ig20Gly can be delivered more quickly than other antibody treatments that are less concentrated. CORE was a study of 36 patients (children and adults) taking Ig20Gly for primary immunodeficiency diseases for 1 year in Germany and Switzerland. The aim of the study was to understand how patients use and experience Ig20Gly as part of their normal treatment. In this study, nearly all patients received Ig20Gly treatment at home, and most patients gave Ig20Gly to themselves once a week. A few patients developed serious bacterial infections while being treated with Ig20Gly, and patients were generally satisfied with the treatment. Overall, the CORE study describes how patients with primary immunodeficiency diseases use Ig20Gly in their daily lives, and shows that Ig20Gly treatment can be tailored to suit each patient's needs. Information from this study will help doctors to support patients in making decisions about their treatment.

Subcutaneous Immunoglobulin 16.5% (Cutaquig®) in Primary Immunodeficiency Disease: Safety, Tolerability, Efficacy, and Patient Experience with Enhanced Infusion Regimens.

PURPOSE: To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens. METHODS: Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient's weekly dose. RESULTS: For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy. CONCLUSIONS: SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.

In-line warming reduces in-line pressure of subcutaneous infusion of concentrated immunoglobulins.

Immunoglobulin replacement therapy is a life-saving treatment in patients with immunodeficiency and effective in the management of autoimmune disorders. Immunoglobulins are administered intravenously or subcutaneously, with the latter route reducing systemic reactions and providing an option for self-infusion, increasing patient convenience, while decreasing patient burden, healthcare utilization, and costs. A major limitation with subcutaneous administrations is the frequency of infusion due to limited volumes administrable into subcutaneous space, necessitating increased drug concentration, absorption, and dispersion. Increasing the concentration of immunoglobulins from 10 to 20% halves the required volume, but leads to higher dynamic viscosity, limiting infusion rate. Recombinant human hyaluronidase increases dispersion and absorption of immunoglobulins allowing administration of ≤ 600 mL per site, but does not change viscosity. Since the viscosity of fluids depends on temperature, we tested the feasibility of in-line warming of immunoglobulin formulations to physiological temperatures. In vitro analysis showed no negative impact of in-line warming to 38 °C on product quality. Subcutaneous infusion studies in pigs confirmed the feasibility of infusion rates of up to 7.5 mL/min with in-line warmed TAK-881, an immunoglobulin 20% facilitated with recombinant human hyaluronidase. In-line pressures were reduced compared with conventional immunoglobulin 20%, and local tolerance was not altered. Reduction of in-line pressures was more pronounced with thinner needle sets, indicating a potential benefit for patients. In summary, an in in-line warming device can circumvent the limitation of high viscosity, while product quality and local tolerance are maintained. The results of the presented studies warrant further testing in a phase 1 clinical study.

Primary Antibody Immunodeficiency and the Pregnant Patient.

An overview of primary antibody immunodeficiency in pregnancy is presented. Indications for immunoglobulin replacement therapy (IGRT), dosing, and safety considerations are highlighted. Uses of immunizations and antimicrobial therapy are also discussed. In general, IGRT, both intravenous and subcutaneous, is considered safe in pregnancy.

Immunoglobulin replacement therapy in patients with immunodeficiencies: impact of infusion method on patient-reported outcomes.

BACKGROUND: Understanding the impact of different immunoglobulin (Ig) infusion methods (intravenous [IVIg] and subcutaneous [SCIg]) upon treatment experience can potentially facilitate optimization of patient outcomes. Here, the perspective of patients with primary and secondary immunodeficiency diseases (PID and SID, respectively) receiving IVIg and SCIg was evaluated, in terms of treatment satisfaction, accounting for treatment history, using Association des Patients Immunodéficients du Québec (APIQ) survey data. METHODS: The online APIQ survey (shared October 2020-March 2021) of patients with immunodeficiencies in Canada contained 101 questions on: Ig use, history, and detailed infusion characteristics; as well as structured patient-reported outcomes such as treatment satisfaction (via TSQM-9), symptom state (via PASS), general health perception (via GHP), and physical and mental function (via PROMIS). Adult respondents (≥ 18 years old) currently using Ig were compared by their current Ig infusion method (IVIg or SCIg cohort) overall, and in a sub-analysis, the IVIg cohort was compared with the SCIg cohort after stratification by respondents who started SCIg when naïve to Ig ('SCIg naïve') or with previous IVIg experience ('SCIg switch'). RESULTS: In total, 54 respondents currently used IVIg and 242 used SCIg. The average duration per infusion of a weekly SCIg infusion was significantly shorter compared with the average duration of a 3-4 weekly IVIg infusion (p < 0.001). The SCIg cohort was associated with significantly higher scores for the TSQM-9 effectiveness domain compared with the IVIg cohort. The scores for TSQM-9 convenience and global satisfaction domains were similar in the two cohorts. The SCIg cohort was also associated with a significantly higher proportion of respondents who were in an acceptable symptom state and a lower proportion who reported very poor or poor perception of health compared with the IVIg cohort. Further, the SCIg naïve subgroup was associated with significantly higher TSQM-9 effectiveness and convenience domain scores compared with the IVIg cohort, while there was no significant difference between the SCIg switch subgroup and the IVIg cohort in terms of convenience. CONCLUSIONS: A better understanding of how different IgRT administration methods impact treatment experience and satisfaction may assist with informed treatment decision making and ultimately further improvements in patient outcomes.

Therapies in Autoimmune Peripheral Neuropathies beyond Intravenous Immunoglobulin, Plasma Exchange and Corticosteroids: An Analytical Review.

Autoimmune neuropathies are often treatable. First-line immunotherapies include intravenous immunoglobulin (IVIG), plasma exchange and corticosteroids. However, nearly 15-30% of patients are either refractory, partially responsive or chronically dependent on these first-line agents. Lack of full response leads to increased disability in addition to adverse financial implications. Consequently, there is an unmet need for more effective treatments to manage this subset of patients. There has been a remarkable increase in the knowledge about immunopathogenesis, antigenic targets, clinical phenotype correlation, and novel therapeutic agents in the last two decades. These novel agents target specific components of the immune system (humoral, cellular immunity, and complement) and have the potential to improve the management of these disorders. Unfortunately, high-quality evidence from large, controlled studies is scarce considering the relative rarity of these refractory cases, heterogeneity of clinical presentations and ethical concerns limiting the use of a placebo arm. An adaptive clinical trial design in a homogenous cohort with standardized outcomes in multiple centers and the use of historical controls will likely provide valuable scientific evidence about the efficacy and safety of these therapies. In this review, we examine the status of the newer immunotherapies in the treatment of autoimmune neuropathies based on existing data.

Usefulness of subcutaneous immunoglobulin therapy in the management of myasthenia gravis: a retrospective cohort study.

INTRODUCTION: To describe the efficacy of subcutaneous immunoglobulin (SCIg) in patients with myasthenia gravis (MG). METHODS: This was a retrospective study conducted in the neuromuscular referral center of Bordeaux (between January 1, 2014 and March 31, 2021) with MG patients treated with SCIg. The main outcome was SCIg efficacy assessed by the before and after SCIg Myasthenia Gravis Foundation of America (MGFA) clinical classification, the duration of hospitalization and the number of days of orotracheal intubation (OTI). RESULTS: Sixteen patients were included in the study (11 females; 5 males). Nine patients were still treated with SCIg at the end of the study (March 31, 2021) and then underwent prospective follow-up. The average age of the patients was 56.1 (19-83) years. The median duration of MG at onset of SCIg was 37.4 months. Eight patients (50%) remained stable (4 in stage MGFA-IV and 4 in MGFA-III). Eight patients (50%) improved: 3 from MGFA-IV to MGFA-III, 1 from MGFA-IV to MGFA-II, 1 from MGFA-IV to MGFA-I, 2 from MGFA-III to MGFA-II and 1 from MGFA-III to MGFA-I (no patient worsened). The duration of disease progression did not appear to affect the response to SCIg therapy. The number of hospital days per month was significantly reduced after SCIg compared to before, and the number of days in intensive care unit and the number of days of OTI were also reduced. Only minor adverse effects were noted, and 80% of patients were in favor of continuing SCIg. CONCLUSIONS: SCIg is a well-tolerated and useful treatment in MG, offering interesting perspectives in the management of MG patients. However, further large-scale prospective studies are needed to confirm these results.

Immunoglobulin Use for the Management of Painful Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Immunoglobulins (IG) are widely used for the treatment of a variety of immune-mediated diseases. The exact mechanism of action remains unknown, but IG modulate the expression and function of Fc receptors, interfere with complement activation and production of cytokines, neutralize pathogenic autoantibodies, and affect the activation and effector functions of B and T lymphocytes. Immunoglobulins are usually delivered intravenously, and are effective in ameliorating motor symptoms, and/or preventing disease progression in immune-mediated neuropathies, including Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. OBJECTIVE: The aim of this systematic review and meta-analysis was to study the potential of IG for the treatment of painful peripheral neuropathy (PPN). The outcome of interest was the percentage of patients with PPN who achieved pain relief following IG administration. METHODS: We performed a systematic literature search on March 17, 2022, in the PubMed database without any publication date restrictions. We also looked for unpublished or ongoing trials in clinicaltrials.org. Pain reduction following IG treatment had to be within the aims (primary or secondary). RESULTS: The aforementioned literature search strategy revealed five studies (two open-label, three randomized placebo-controlled) eligible to be included. The pooled estimate of the percentage of patients with PPN who received immunoglobulins and reported pain relief was found to be 65% (95% CI 58-71%). The likelihood of achieving pain relief with immunoglobulin treatment was 2.9 times higher (95% CI 1.6-5.2) compared to placebo (p = 0.0003). CONCLUSION: The use of IG for the treatment of pain due to peripheral neuropathy has a potential therapeutic benefit. Further studies across patients with different types of painful peripheral neuropathy are needed to better characterize this effect. Registration number on PROSPERO: CRD42022319614.

SCIG administration: A promising and patient convenient alternative for those receiving long-term IVIG.

BACKGROUND: Intravenous immunoglobulin (IVIG) therapy has been used as antibody replacement therapy in primary immunodeficiency diseases (PID) for more than 50 years. In this study, we aimed to define IVIG usage and adverse reactions and complications in PID and explain how subcutaneous immunoglobulin (SCIG) replacement therapy is an alternative that improves the patient experience. In addition, the additional nursing responsibilities associated with this service were also identified. METHODS: Data and service satisfaction surveys for the last 10 years were reviewed from the Allergy and Immunology Division log registry for those on IVIG and SCIG. RESULTS: IVIG practice: Most patients currently on IVIG in our unit have PID. Adverse reactions occur during the initial 30 to 60 minutes of the infusion and are mild and self-limited. Infusion reactions are more likely to occur in patients receiving IVIG for the first time. Infusion-related complications included pyrogenic reactions, allergic reactions, and vasomotor symptoms. Complications reported in the literature such as the transmission of blood-borne pathogens and other serious complications, including thrombotic events, renal adverse events, and aseptic meningitis were never reported. Pyrogenic reactions occurred at a rate ≥ 100 mL/hr in at least 3 patients, and a slower infusion rate of ≤ 75 mL/hr mitigated this rate-related complication. SCIG program: This program started in Qatar in 2017. Usually, the clinician assesses and evaluates several factors to help select candidates for this therapy, including the perceptions of inconvenience and/or pain of IV infusions, presence of difficult vein access, and other relevant clinical and social factors. Once training in the appropriate techniques has been accomplished (3-6 sessions), it is most often self-administered in the home setting by the patient or a parent for a child. Table 1 summarizes patients on SCIG. Additional nursing responsibilities: The nursing role in subcutaneous IgG administration is primarily that of an educator and to help the patient/family become independent. This can be achieved by the assessment of appropriate patient selection for self-administration. Determining which patients are suitable include adequate patient education with return demonstration of the necessary skill set, monitoring parameters, educating patients about their medication, and providing educational resources and support. CONCLUSION: SCIG administration can be a convenient alternative for patients with PID receiving long-term IVIG.

An update on the use of immunoglobulins as treatment for myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) is an antibody mediated disease where pathogenic antibodies interact with the acetylcholine receptor or other proteins at the post-synaptic neuromuscular junction. There is growing evidence that immunoglobulin infusions are beneficial for clinical exacerbations and chronic refractory disease and may be an option for patients unresponsive to conventional immunosuppressive therapies. AREAS COVERED: We performed an extensive literature review, looking for evidence on the use of immunoglobulins for the treatment of MG, by conducting a search in MEDLINE (1946 to present), EMBASE (1947 to present) and Clinicaltrials.gov. We have included studies on the use of intravenous immunoglobulins (IVIG) and subcutaneous immunoglobulins (SCIG) for acute deterioration and chronic disease. EXPERT OPINION: The use of IVIG in MG provides an option for rapid improvement in critical deterioration, being preferred over more invasive and less available therapies such as plasmapheresis. For refractory MG, the addition of IVIG can improve a patient's status and reduce the dosage of immunosuppressive medications. The alternative of SCIG is also effective and has advantages of infusion time flexibility, fewer side-effects, and patient independence. The safety and efficacy of both interventions, patient preferences and quality of life may direct therapeutic choices in the future.

Adaptive data-driven fault-tolerant control strategy for optimal power extraction in presence of broken rotor bars in wind turbine.

Broken rotor bars of a Squirrel Cage Induction Generator (SCIG) impact significantly the quality and quantity of produced electrical energy from Wind Energy Conversion Systems (WECS) because: (1) they change the characteristics of SCIG entailing the invalidity of the designed Maximum Power Point Trucking (MPPT) control and pitch angle control, (2) they increase mechanical and thermal stresses, as well as the harmonic content in stator currents. Therefore, this paper proposes an efficient fault tolerant control strategy in order to mitigate the aforementioned consequences. This strategy is based on a hybrid (mechanic-electric) fault tolerant control (FTC) allowing obtaining optimal power extraction in presence of broken rotor bars. A failure (one or two broken bars) is detected in early stage based on the use of a data-driven (machine learning) approach. The latter uses a discriminative feature space (frequency and magnitude of stator harmonic currents) in order to represent and separate the normal operation mode from faulty modes (broken bars). Simulations using MATLAB demonstrated a nominal current in healthy rotor bars in wind turbine operation zone-3 and new optimal power extraction despite one or two broken bars.