Population pharmacokinetics of immunoglobulin G after intravenous, subcutaneous, or hyaluronidase-facilitated subcutaneous administration in immunoglobulin-naive patients with primary immunodeficiencies.

Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiencies with antibody deficiencies. Intravenous (IVIG), subcutaneous (SCIG), and hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) therapies differ in their pharmacokinetic (PK) profiles, administration routes, and dosing regimens. Information on use of subcutaneous therapy in IgG treatment-naive patients is limited. This study used population pharmacokinetic (popPK) model-based simulations to characterize IgG PKs in IgG-naive patients with varying disease severity across several IVIG, SCIG, and fSCIG dosing regimens. An integrated popPK model, developed and validated using data from eight clinical trials, was utilized to simulate scenarios that varied by therapy, loading regimen, maintenance dose (equivalent to 400, 600, or 800 mg/kg every 4 weeks [Q4W]), and baseline endogenous total IgG concentration (1.5 or 4.0 g/L). Simulations were performed for age groups of 2-<6, 6-<12, 12-<18, and ≥18 years. Steady-state serum trough IgG concentrations (Cmin,ss), proportion of patients achieving Cmin,ss ≥ 7 g/L, and days taken to reach this threshold were summarized. SCIG provided greater mean Cmin,ss values than IVIG and fSCIG for any scenario. Across all therapies, Cmin,ss tended to increase with age, dose, and endogenous concentration. Although the findings are model-based and not a summarization of real-world observations, doses ≥ 800 mg/kg Q4W with corresponding loading regimens are likely to be clinically appropriate for achieving target IgG concentrations in treatment-naive patients in a timely manner, especially at low endogenous starting concentrations. Therapy-specific dose adjustment based on baseline endogenous IgG concentration, clinical status, and patient characteristics may be warranted.

Dosing Strategy of Immunoglobulin (IgG) Replacement Therapies in Obese and Overweight Patients with Primary Immunodeficiency Diseases (PIDDs): A Meta-Analysis of Clinical Trials.

The current dosing strategy of immune globulin products for the treatment of primary immunodeficiency diseases (PIDDs) in the USA is based on total body weight (BW). The aim of our study was to assess the relationship between dose and trough level, and to determine whether an alternative dosing strategy should be considered for patients who are overweight or obese. We analyzed data in a total of 533 patients from 11 studies. We modeled the relationship between trough level and dose per week using a linear mixed model. We used an over-dispersed Poisson model to model the relationship between infection and trough level. In these analyses, we then combined the study-specific treatment effects using a random-effect or fixed-effect model. The mean administered dose per week was 9.77, 14.00, or 18.17 g in patients who were normal weight, overweight, or obese, respectively. Compared with a patient of normal weight, a 1 g increase in dose per week in a patient who was overweight was associated with a smaller increase in the trough level, 0.08 g/L less (95%CI -0.14 to -0.03 g/L), and a 1 g increase in dose per week in a patient who was obese was associated with a much smaller increase in trough level, 0.01 g/L less (95% CI -0.07 to 0.06 g/L). Last, for a 1 unit (g/L) increase in trough level, the expected number of infections remained the same, with a multiplicative factor of 1.01 (95%CI 0.98-1.04). Overall, we found no compelling evidence to justify a reconsideration of the current dosing strategy based on total BW for patients with PIDDs who are overweight or obese.

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.

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.

A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome.

BACKGROUNDWarts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined.METHODSIn this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF (G-CSF, the standard of care for severe congenital neutropenia). The treatment order was randomized for each patient.RESULTSPlerixafor was nonsuperior to G-CSF for TISS (P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/µL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/µL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events.CONCLUSIONPlerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome.TRIAL REGISTRATIONClinicaltrials.gov NCT02231879.FUNDINGThis study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

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.

Quality of Life Evaluation in Saudi Arabian Pediatric Patients with Primary Immunodeficiency Diseases Receiving 20% Subcutaneous IgG Infusions at Home.

BACKGROUND AND AIMS: Subcutaneous immunoglobulin (SCIG) home infusion is widely used as an alternative to intravenous immunoglobulin (IVIG). This study aimed to determine the quality of life (QoL) of patients with primary immunodeficiency (PID) after switching to home-based SCIG. METHODS: In this prospective open-label single-center study, QoL was determined using the validated Arabic version of the Child Health Questionnaire at baseline and 3 and 6 months after switching from IVIG to SCIG. RESULTS: Twenty-four patients were recruited from July 2018 to August 2021, including 14 females and 10 males. The median age of the patients was 5 years (range, 0-14 years). The patients' diagnoses included severe combined immunodeficiency, combined immunodeficiency, agammaglobulinemia, Omenn syndrome, immunodysregulation, hyper-IgE syndrome, common variable immunodeficiency, and bare lymphocyte syndrome. The median duration on IVIG before inclusion was 40 months (range, 5-125 months). The QoL score showed a significant improvement in the patients' global health at 3 and 6 months compared with those at baseline and a significant improvement in the patients' general health at 3 and 6 months compared with that at baseline. The mean baseline serum IgG trough level was 8.8 ± 2.1 g/L. The mean serum IgG level was significantly higher on SCIG at both 3 and 6 months (11.7 ± 2.3 and 11.7 ± 2.5 g/L, respectively). CONCLUSIONS: This is the first study involving an Arab population to show improvement in the QoL of patients with PID after switching from hospital-based IVIG to home-based 20% SCIG.

Does Trimethoprim-Sulfamethoxazole prophylaxis induce myelosuppression in primary immune deficiency disease patients; A retrospective, 3 groups comparative study.

BACKGROUND: The possible myelosuppression side effect of Trimethoprim-Sulfamethoxazole (TMP-SMX) on primary immune deficiency (PID) patients has not been established yet. OBJECTIVE: Identify if the PID patients are at higher risk of developing myelosuppression secondary to the use of TMPSMX. METHODS: Retrospective, three groups study, of PID patients (on and off TMP-SMX prophylaxis) and urinary tract infection (UTI) patients received prophylaxis TMP-SMX. Data about CBC results (WBC, ANC, Lymphocytes, RBC, Hemoglobin, and Platelet counts) at baseline, first, and maximum myelosuppression observed during the period of TMP-SMX administration were collected. RESULTS: A total of 122 patients were included in this study (41 PID patients on TMP-SMX prophylaxis, 45 PID patients not on TMP-SMX prophylaxis, and 36 UTI patients on prophylaxis TMP-SMX). There are significant differences noticed in the percentage of patients who developed clinical myelosuppression (i.e. less than normal value for age) in ANC (39.0% vs. 8.9% vs. 16.7%, p = 0.002), RBC (36.6% vs. 13.3% vs. 13.9%, p = 0.014), WBC (41.5% vs. 13.3% vs. 13.9%, p = 0.003), and platelet (24.4% vs. 15.6% vs. 2.8%, p = 0.028) in group 1, 2, and 3, respectively. Significant difference in myelosuppression between the groups was most likely due to the combination of TMP-SMX effect on PID patients rather than the disease or the drug itself. CONCLUSIONS: Primary immune deficiency (PID) patients are at higher risk of developing myelosuppression secondary to TMP-SMX prophylaxis (especially ANC) comparing to immune-competent patients or other PID patients who did not receive prophylactic TMP-SMX. Future larger prospective study is required to confirm this association.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children.

PURPOSE: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID. METHODS: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient's pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated. RESULTS: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates. CONCLUSION: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID. TRIAL REGISTRATION: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.

Gammaglobulina subcutánea: Revisión sistemática / Subcutaneous gamma globulin: A systematic review

Las inmunodeficiencias primarias constituyen enfermedades determinadas genéticamente, caracterizadas por la alteración cuantitativa y/o funcional de distintos mecanismos implicados en la respuesta inmunitaria. Algunas de ellas se caracterizan por una alteración en la producción de anticuerpos, por lo que algunos pacientes se benefician con la administración supletoria de gammaglobulina, la cual se administra mayormente por vía endovenosa, siendo la vía subcutánea una alternativa terapéutica. La siguiente revisión sistemática tiene por objetivo determinar si la gammaglobulina subcutánea tiene alguna ventaja frente al clásico uso de gammaglobulina endovenosa, en pacientes pediátricos con inmunodeficiencias primarias, revisando la bibliografía disponible hasta la actualidad (AU)

Primary immunodeficiencies are genetically determined diseases characterized by the quantitative and/or functional alteration of different mechanisms involved in the immune response. Some of these diseases are characterized by an alteration in the antibody production and therefore some patients benefit from the supplementary administration of gamma globulin, which is mostly administered intravenously, with the subcutaneous route being a therapeutic alternative. The following systematic literature review aims to determine whether subcutaneous gamma globulin has any advantage over the classic use of intravenous gamma globulin in pediatric patients with primary immunodeficiencies (AU)

Évaluation d'HyQviaMC (immunoglobulines humaines normales à 10 % et hyaluronidase): Déficit immunitaire primaire et secondaire / HyQvia™ Assessment (10% Human Normal Immunoglobulins and Hyaluronidase): Primary and Secondary Immunodeficiency

MANDAT: À la demande du fabricant Takeda Canada Inc., l'Institut national d'excellence en santé et en services sociaux (INESSS) a procédé à l'évaluation du produit HyQviaMC, une combinaison d'immunoglobulines normales humaines à 10 % et d'hyaluronidase, qui s'administre par voie sous-cutanée (s.c.). Ce produit est indiqué pour le traitement substitutif du déficit immunitaire humoral primaire (DIP) et du déficit immunitaire humoral secondaire (DIS) chez les adultes. Il s'agit de la première évaluation de cette préparation d'immunoglobulines. DÉMARCHE D'ÉVALUATION: Une revue des données issues de la littérature et de celles fournies par le fabricant a été réalisée afin d'évaluer l'efficacité, l'innocuité et l'efficience d'HyQviaMC. Des données contextuelles et expérientielles issues de la consultation d'experts sont également présentées. BESOIN DE SANTÉ: Idéalement, les traitements du DIP et du DIS devraient offrir une protection contre les infections comparable à la normale. Sont également souhaitables des traitements qui préviennent davantage les risques d'infection par rapport aux thérapies prophylactiques actuelles et qui favorisent l'atténuation des contraintes liées aux perfusions répétées d'immunoglobulines intraveineuses (i.v.) ou s.c. L'approvisionnement et la disponibilité des immunoglobulines de remplacement sont précaires. De plus, la demande ne cessant d'augmenter au Québec, il apparaît important de sécuriser plusieurs sources d'immunoglobulines. Actuellement, 8 produits sont inscrits sur la Liste des produits du système du sang du Québec, dont 3 s'administrent par voie s.c. RÉSULTATS: Efficacité: Les études pivot, de prolongation et en contexte réel de soins montrent que le taux annuel d'infections bactériennes aiguës sévères était inférieur à la valeur seuil de 1 chez les patients atteints de DIP ou de DIS traités avec HyQviaMC. Le taux annuel d'infection global variait de 0,88 à 2,99 selon les études. Ces résultats sont comparables à ceux des autres préparations d'immunoglobulines actuellement disponibles au Québec. La qualité des études considérées varie de faible à modérée. La force de la preuve est faible. Innocuité: Des événements indésirables faibles à sévères ont été observés au cours des études pivot et de prolongation, dont des cas de thrombose jugés non liés au traitement. L'absence de conséquences cliniques liées aux anticorps anti-hyaluronidase ainsi que l'usage historique d'HyQviaMC en Europe et aux États-Unis semblent indiquer qu'il ne serait pas nécessaire de surveiller le taux d'anticorps contre l'hyaluronidase chez les patients traités avec HyQviaMC. La qualité méthodologique des études considérées varie de faible à modérée. La force de la preuve est très faible. Qualité de vie: La voie d'administration des immunoglobulines i.v. et s.c. ne semblait pas avoir un effet important sur la qualité de vie liée à la santé. La qualité méthodologique de l'étude considérée est modérée. La force de la preuve est modérée. Perspective des experts: Malgré la faible qualité des études, les experts consultés jugent l'efficacité d'HyQviaMC à prévenir les infections et son profil d'innocuité comparables à ceux des immunoglobulines présentement disponibles. Selon les experts, l'effet d'HyQviaMC sur la qualité de vie des patients est comparable à celui des autres préparations d'immunoglobulines. Perspective des patients: Le traitement de remplacement des immunoglobulines par perfusion i.v. (IgIV) ou par injection s.c. (IgSC) est vécu comme un fardeau par de nombreux patients. Certains patients aimeraient bénéficier d'une thérapie comme HyQviaMC, qui peut être administrée à domicile tout en offrant la même fréquence d'administration que les IgIV. Aspect organisationnel: L'administration d'HyQviaMC requiert que les patients soient adéquatement formés. Les experts soulignent que l'utilisation d'HyQviaMC requiert un niveau d'habileté plus élevé que celui exigé pour l'administration d'une IgSC conventionnelle. Un programme de soutien aux patients est offert par le fabricant. Néanmoins, selon les experts, il serait utile d'élaborer un protocole pour les soins à domicile des centres locaux de services communautaires (CLSC). ANALYSES ÉCONOMIQUES: Analyse d'efficience: Au prix soumis par le fabricant, le traitement par HyQviaMC est une option thérapeutique moins efficiente que les autres immunoglobulines actuellement distribuées au Québec. Analyse d'impact budgétaire: L'ajout d'HyQviaMC à la Liste des produits du système du sang du Québec pourrait entraîner une augmentation des dépenses estimée à 11 M$ pour les trois prochaines années.

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

PURPOSE: Activated phosphoinositide 3-kinase δ syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort. METHODS: Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation. RESULTS: Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis. CONCLUSION: Clinical spectrum of APDS is heterogeneous. This cohort's high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.

Primary Immune Deficiency: Patients' Preferences for Replacement Immunoglobulin Therapy.

Purpose: Immunoglobulin (Ig) replacement therapy is an important life-saving treatment modality for patients with primary antibody immune deficiency disorders (PAD). IVIG and SCIg are suitable alternatives to treat patients with PAD but vary in key ways. Existing evidence on patient preferences for Ig treatments given the complexities associated with IVIG and SCIg treatment is limited and fails to account for variations in preferences across patients. For this reason, we sought to evaluate PAD patient preferences for features of IVIG and SCIg across different patient characteristics. Materials and Methods: 119 PAD patients completed a discrete-choice experiment (DCE) survey. The DCE asked respondents to make choices between carefully constructed treatment alternatives described in terms of generic treatment features. Choices from the DCE were analyzed to determine the relative influence of attribute changes on treatment preferences. We used subgroup analysis to evaluate systematic variations in preferences by patients' age, gender, time since diagnosis, and treatment experience. Results: Patients were primarily concerned about the duration of treatment side effects, but preferences were heterogeneous. This was particularly true around administration features. Time since diagnosis was associated with an increase in patients' concerns with the number of needles required per infusion. Also, patients appear to prefer the kind of therapy they are currently using which could be the result of properly aligned patient preferences or evidence of patient adaptive behavior. Conclusions: Heterogeneity in preferences for Ig replacement treatments suggests that a formal shared decision making process could have an important role in improving patient care.

Ten-year population trends of immunoglobulin use, burden of adult antibody deficiency and feasibility of subcutaneous immunoglobulin (SCIg) replacement in Hong Kong Chinese.

Background: Adult antibody deficiency remains under-recognised and under-studied - especially among Asian populations. Patterns of immunoglobulin use and the feasibility of subcutaneous immunoglobulin (SCIg) replacement among Chinese patients remains unclear. Objective: To investigate the trends of immunoglobulin use, burden of adult antibody deficiency and the outcomes of patients on SCIg compared to intravenous immunoglobulin (IVIg) replacement in Hong Kong through a retrospective observational study. Methods: Population-wide data of immunoglobulin recipients in Hong Kong between 2012 and 2021, and longitudinal clinical data of adult immunodeficiency patients at Queen Mary Hospital were collected and analysed. Results: Total immunoglobulin consumption and recurrent immunoglobulin recipients increased continuously from 175,512g to 298,514g (ρ=0.99, p<0.001) and 886 to 1,508 (ρ=0.89, p=0.001) between 2012-21 in Hong Kong. Among 469 immunoglobulin recipients at Queen Mary Hospital in 2021, 344 (73.3%) were indicated for replacement. Compared to those on IVIg (n=14), patients on SCIg replacement (n=8) had fewer immunodeficiency-related hospitalisations (IRR=0.11) and shorter duration of hospitalisation stay (IRR=0.10) per year, as well as better quality of life (SF-36v2 Health Survey and Life Quality Index). Estimated annual healthcare cost of SCIg replacement per patient was lower than that of IVIg (HKD196,850 [USD25,096] vs HKD222,136 [USD28,319]). Conclusion: There was a significantly increasing burden of adult antibody deficiency and immunoglobulin consumption in Hong Kong. SCIg was feasible and more cost-effective when compared to IVIg, with SCIg patients experiencing better clinical outcomes and quality of life. Future prospective studies to confirm the long-term efficacy and superiority of SCIg are required.

Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases.

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871, NCT00814320, NCT01175213 (ClinicalTrials.gov).