Search

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (AEs). Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs., (© 2024. The Author(s).)

Background: Limited data exist regarding adverse drug events (ADEs) in the outpatient setting. The objective of this study was to determine the incidence, severity, and preventability of ADEs in the outpatient setting and identify potential prevention strategies., Methods: We conducted an analysis of ADEs identified in a retrospective electronic health records review of outpatient encounters in 2018 at 13 outpatient sites in Massachusetts that included 13 416 outpatient encounters in 3323 patients. Triggers were identified in the medical record including medications, consultations, laboratory results, and others. If a trigger was detected, a further in-depth review was conducted by nurses and adjudicated by physicians to examine the relevant information in the medical record. Patients were included in the study if they were at least 18 years of age with at least one outpatient encounter with a physician, nurse practitioner or physician's assistant in that calendar year. Patients were excluded from the study if the outpatient encounter occurred in outpatient surgery, psychiatry, rehabilitation, and paediatrics., Results: In all, 5% of patients experienced an ADE over the 1-year period. We identified 198 ADEs among 170 patients, who had a mean age of 60. Most patients experienced one ADE (87%), 10% experienced two ADEs and 3% experienced three or more ADEs. The most frequent drug classes resulting in ADEs were cardiovascular (25%), central nervous system (14%), and anti-infective agents (14%). Severity was ranked as significant in 85%, 14% were serious, 1% were life-threatening, and there were no fatal ADEs. Of the ADEs, 22% were classified as preventable and 78% were not preventable. We identified 246 potential prevention strategies, and 23% of ADEs had more than one prevention strategy possibility., Conclusions: Despite efforts to prioritise patient safety, medication-related harms are still frequent. These results underscore the need for further patient safety improvement in the outpatient setting., Competing Interests: Competing interests: DWB reports grants and personal fees from EarlySense, personal fees from CDI Negev, equity from ValeraHealth, equity from Clew, equity from MDClone, personal fees and equity from AESOP, personal fees and equity from Feelbetter, equity from Guided Clinical Solutions and grants from IBM Watson Health, outside the submitted work. DWB has a patent pending (PHC-028564 US PCT), on intraoperative clinical decision support., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A risk factor for a potentially fatal ventricular arrhythmia Torsade de Pointes is a prolongation in the heart rate-corrected QT interval (QTc) ≥ 500 milliseconds (ms) or an increase of ≥ 60 ms from a patient's baseline value, which can cause sudden cardiac death. The Tisdale risk score calculator uses clinical variables to predict which hospitalized patients are at the highest risk for QTc prolongation., Objective: To determine the rate of overridden QTc drug-drug interaction (DDI)-related clinical decision support (CDS) alerts per patient admission and the prevalence by Tisdale risk score category of these overridden alerts. Secondary outcome was to determine the rate of drug-induced QTc prolongation (diQTP) associated with overrides., Methods: Our organization's enterprise data warehouse was used to retrospectively access QTc DDI alerts presented for patients aged ≥ 18 years who were admitted to Brigham and Women's Hospital during 2022. The QTc DDI CDS alerts were included if shown to a physician, fellow, resident, physician assistant, or nurse practitioner when entering the order in inpatient areas for patients with a length of stay of at least 2 days. Variables collected for the Tisdale calculator included age, sex, whether patient was on a loop diuretic, potassium level, admission QTc value, admitting diagnosis of acute myocardial infarction, sepsis, or heart failure, and number of QTc-prolonging drugs given to the patient., Results: A total of 2649 patients with 3033 patient admissions had 18,432 QTc DDI alerts presented that were overridden. An average of 3 unique QTc DDI alerts were presented per patient admission and the alerts were overridden an average of 6 times per patient admission. Overall, 6% of patient admissions were low risk (score ≤ 6), 64% moderate risk (score 7-10), and 30% high risk (score ≥ 11) of QTc prolongation. The most common QTc DDI alerts overridden resulting in an diQTP were quetiapine and propofol (11%) and amiodarone and haloperidol (7%). The diQTP occurred in 883 of patient admissions (29%) and was more frequent in those with higher risk score, with 46% of patient admissions with diQTP in high risk, 23% in moderate risk, and 8% in low risk., Conclusion: Use of the Tisdale calculator to assess patient-specific risk of QT prolongation combined with CDS may improve overall alert quality and acceptance rate, which may decrease the diQTP rate., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A food reaction history is the basis of food allergy diagnoses. Several levels of food allergy diagnostic testing can confirm or refute the presence of food allergy. The choice of food allergy testing modality should be informed by the reaction history and determined by the testing goals. Testing modalities include skin-prick testing, in vitro specific immunoglobulin E testing, component-resolved testing, epitope threshold testing, and basophil activation testing. The goal of food allergy testing may be merely to confirm the diagnosis of food allergy or may be used to guide passive (avoidance) or active (allergen immunotherapy) management. The most appropriate diagnostic path should consider testing predictive value, the goal of the evaluation, patient and family food allergy anxiety, and cost. Peanut allergy testing provides an algorithm for testing pathways., Competing Interests: R.L. Wasserman is an advisor for Grifols, CSL Behring; speaker for CSL Behring, Grifols, Takeda, GSK; consultant for Elevare Consultants, Evolve Biologics, Grifols, Korean Green Cross, Takeda and researcher for Coor Pharmaceuticals, (Copyright © 2024, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

Background: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective., Objective: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians., Methods: A survey in Canada and the United States involved families currently enrolled in food OIT programs., Results: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001)., Conclusions: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process., Objective: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form., Methods: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed., Results: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form., Conclusion: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the ability of DynaMedex, an evidence-based drug and disease Point of Care Information (POCI) resource, in answering clinical queries using keyword searches., Methods: Real-world disease-related questions compiled from clinicians at an academic medical center, DynaMedex search query data, and medical board review resources were categorized into five clinical categories (complications & prognosis, diagnosis & clinical presentation, epidemiology, prevention & screening/monitoring, and treatment) and six specialties (cardiology, endocrinology, hematology-oncology, infectious disease, internal medicine, and neurology). A total of 265 disease-related questions were evaluated by pharmacist reviewers based on if an answer was found (yes, no), whether the answer was relevant (yes, no), difficulty in finding the answer (easy, not easy), cited best evidence available (yes, no), clinical practice guidelines included (yes, no), and level of detail provided (detailed, limited details)., Results: An answer was found for 259/265 questions (98%). Both reviewers found an answer for 241 questions (91%), neither found the answer for 6 questions (2%), and only one reviewer found an answer for 18 questions (7%). Both reviewers found a relevant answer 97% of the time when an answer was found. Of all relevant answers found, 68% were easy to find, 97% cited best quality of evidence available, 72% included clinical guidelines, and 95% were detailed. Recommendations for areas of resource improvement were identified., Conclusions: The resource enabled reviewers to answer most questions easily with the best quality of evidence available, providing detailed answers and clinical guidelines, with a high level of replication of results across users., (Copyright © 2024 Rachel Leah Wasserman, Diane L. Seger, Mary G. Amato, Zoe Co, Aqsa Mugal, Angela Rui, Pamela M. Garabedian, Marlika Marceau, Ania Syrowatka, Lynn A. Volk, David W. Bates.)

Aim: To describe development of a shared decision making (SDM) aid in treating primary immunodeficiency diseases (PID) with immunoglobulin replacement therapy (IGRT). Materials & methods: Expert engagement and qualitative formative research informed development. IGRT administration features were prioritized using object-case best-worst scaling (BWS) methodology. The aid was assessed by US adults self-reporting PID and revised following interviews/mock treatment-choice discussions with immunologists. Results: Patients participating in interviews (n = 19) and mock treatment-choice discussions (n = 5) deemed the aid useful/accessible and supported the utility of BWS, with content and BWS exercises refined following participant feedback. Conclusion: Formative research led to an improved SDM aid/BWS exercise, and illustrated how the aid may improve treatment decision making. The aid may help less-experienced patients and facilitate efficient SDM.

Food allergy is a significant health problem affecting approximately 8% of children and 11% of adults in the United States. It exhibits all the characteristics of a "complex" genetic trait; therefore, it is necessary to look at very large numbers of patients, far more than exist at any single organization, to eliminate gaps in the current understanding of this complex chronic disorder. Advances may be achieved by bringing together food allergy data from large numbers of patients into a Data Commons, a secure and efficient platform for researchers, comprising standardized data, available in a common interface for download and/or analysis, in accordance with the FAIR (Findable, Accessible, Interoperable, and Reusable) principles. Prior data commons initiatives indicate that research community consensus and support, formal food allergy ontology, data standards, an accepted platform and data management tools, an agreed upon infrastructure, and trusted governance are the foundation of any successful data commons. In this article, we will present the justification for the creation of a food allergy data commons and describe the core principles that can make it successful and sustainable., (Published by Elsevier Inc.)

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay., Competing Interests: SO’R was employed by New Columbia Capital, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Alpan, Wasserman, Kim, Darter, Shah, Jones, McNeil, Li, Ispas, Rathkoph, Perez, Siri, O'Connor, Plassmeyer, Romito, Pettibone, O'Reilly, Sønder and Marti.)

While the historic management of food allergy includes avoidance strategies and allergic reaction treatment, oral immunotherapy (OIT) approaches have become more commonly integrated into therapeutic approaches. International guidelines, phase 3 trials and real-world experience have supported the implementation of this procedure. However, OIT is an elective, rarely curative procedure with inherent risks that necessitates an increased degree of health literacy for the patients and families. Families assume the responsibility of amateur healthcare providers to ensure the daily safe administration of the allergenic food. As such, it is incumbent upon physicians to ensure that families are prepared for this role. A thorough educational and shared decision-making approach is necessary during the counselling and consent process to adequately inform the families. Educated discussion about the efficacy and patient-centred effectiveness, therapeutic alternatives and family goals is required to align physician and patient expectations. A frank discussion about the struggles, practical challenges, risks and contraindications can help to develop an understanding of the risk mitigation strategies employed to maintain safety. Physicians should develop a proactive approach to educate families about this, at times, burdensome procedure. This educational approach should encourage ongoing support starting prior to consent through the maintenance visits. By preparing families for their unique management role, physicians can help ensure the safe and successful integration of OIT into the therapeutic offering for the management of food allergies., (© 2022 John Wiley & Sons Ltd.)

Aim: A novel, Investigational Wearable Infusor (IWI) was evaluated in a randomized, controlled, crossover, open-label study to determine if its delivery of subcutaneous immunoglobulin (IgPro20) achieved a comparable area under the concentration-time curve (AUC) for immunoglobulin G (IgG) versus the Crono S-PID-50 infusion pump (CP). EudraCT: 2016-003798-16. Materials & methods: Patients with primary immunodeficiency (PID) were randomized to receive IgPro20 in Sequence 1 (CP/IWI) or 2 (IWI/CP). The primary end point was AUC for IgG during the final week of each 4-week period. Results: 23 patients were enrolled. Evaluation of area under the concentration-time curve from time 0 (pre-infusion) to 7 days after infusion (AUC 0-7 days ) (IWI: 1806 h*g/l; CP: 1829 h*g/l) and geometric mean ratio indicated comparable AUCs for IgG for both devices. Conclusion: Similar IgG exposure, indicated by AUC values, can be achieved with IgPro20 using the IWI or CP in PID.

There is limited data addressing the optimal dose, dosing frequency, and duration of OIT maintenance. Using higher maintenance doses, more frequent dosing, and a long dosing duration makes it more likely that sustained unresponsiveness will be achieved but also increases the burden of care on the OIT patient and family. The OIT maintenance regimen should be individualized based on the treatment goals of the patient and family., (Copyright © 2022, The Author(s). Published by OceanSide Publications, Inc., U.S.A.)

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).

Background: Immunoglobulin replacement therapy (IGRT) is the foundation of treatment for the majority of patients with primary immunodeficiency. Clinical history and laboratory evaluation define the patients for whom IGRT is necessary and appropriate. During the 70 years since the first patient was treated, new products have led to the development of several modes of administration that facilitate the individualization of treatment that enables the optimization of care. Objective: The objective was to explain the assessment of candidates for IGRT and approaches to reevaluating recipients of IGRT to decide on the need to continue treatment and to review the approaches to optimize IGRT. Methods: The relevant literature was reviewed in the context of the author's experience supervising > 20,000 IGRT treatments over a 40-year period. Results: Providing the most appropriate form of IGRT for individual patients ameliorates disease and lessens the burden of care for patients with primary immunodeficiency. Conclusion: IGRT is safe and effective when used to treat patients with primary immunodeficiency who meet established and appropriate clinical and laboratory criteria.

Background: Advances in oral immunotherapy (OIT) have led to recently expanded treatment options for food allergy (FA) patients. However, to inform future outreach efforts and ensure equitable access to emerging treatments, a greater understanding of current OIT-related awareness, attitudes, and experiences is needed., Objective: To characterize current OIT awareness, attitudes, and experiences among a nationally representative sample of U.S. adults with FA and parents/caregivers of pediatric patients., Methods: A probability-based sample of U.S. adults and parents/caregivers of children with FA was surveyed about OIT-related knowledge, attitudes, and experiences., Results: Surveys were completed by respondents (n = 781) from all 50 states. Overall, 72% did not know what OIT was prior to the survey. Respondents from households earning over $100,000 or with a college degree each had significantly greater odds of reporting any OIT awareness compared with lower-income (odds ratio 2.0; 95% confidence interval 1.2-3.4) and non-college-educated (odds ratio 1.9; 95% confidence interval 1.2-3.0) respondents. Among respondents familiar or unfamiliar with OIT, 54% and 34%, respectively, reported their expected treatment outcome was to obtain protection against accidental exposure. Among respondents familiar or unfamiliar with OIT, 38% and 35%, respectively, reported their expected treatment outcome to be curing the allergy. Furthermore, 55% of OIT unfamiliar respondents said they would not be comfortable initiating a conversation with their health care provider about their suitability for OIT., Conclusions: This study shows that, among a nationally representative sample of FA patients and pediatric caregivers, awareness of OIT is low, and over 95% of patients lack personal experience with OIT. Furthermore, the data suggest current OIT awareness is disproportionately elevated among wealthier, more highly educated respondents., (Copyright © 2021. Published by Elsevier Inc.)

Background: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician., Methods: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions., Results: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory., Conclusions: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range., (© 2021 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals LLC on behalf of International Clinical Cytometry Society.)

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov: NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency., Competing Interests: AE has participated in advisory boards for ALK Abello, AstraZeneca, Aralez, Bausch Health, LEO Pharma, Merck, Novartis, and Pfizer; has served as a speaker for ALK Abello, The ACADEMY, Aralez, AstraZeneca, Medexus, and Mylan; and has been a consultant to Bayer LLC and Regeneron. Her institution has received research grants from ALK Abello, Aralez, AstraZeneca, Bayer LLC, GC Pharma, Medexus, Novartis, Sanofi and Regeneron. WL has served as a consultant for Accordant, BioCryst, Biomarin, CSL Behring, Express Scripts, Fresenius Kabi, Intellia, Kalvista, Magellan, Optum, Pharming, Pharvaris, and Shire/Takeda; serves as a speaker for BioCryst, CSL Behring, Pharming, Shire/Takeda, Grifols, Astra Zeneca, Sanofi/Regeneron and GSK; and receives grants or research support from ALK, BioCryst, CSL Behring, Gossamer, GC Pharma, Grifols, Ionis, Kalvista, Kedrion, Shire/Takeda and Therapure. He is a member of the US Hereditary Angioedema Association Medical Advisory Board. RW serves as an investigator for CSL Behring, Grifols, Kedrion, GC Pharma, Takeda, and TherapureBio; serves as a consultant for ADMA Biologicals, Grifols, GC Pharma, Takeda, and TherapureBio; and serves as a speaker for CSL Behring, Grifols, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from GC Pharma, Korea. The funder was involved in the study design, analysis and interpretation of data, review of the manuscript, and the decision to submit the manuscript for publication., (Copyright © 2021 Perez, Hébert, Ellis, Alpan, Lumry, Shapiro, Suez, Mandujano and Wasserman.)

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Nut-based milks and yogurts are gaining popularity, but may not offer the same benefits as dairy yogurts to consumers . Cashew nuts often cause severe allergic reactions, and cashew nut allergens are stable to several types of processing. To compare its characteristics to dairy yogurt and characterize the effects of fermentation on the Ana o 1-3 cashew nut allergens, a commercial yogurt made from cashew nuts (Cashewgurt) was evaluated for microbiological, physiochemical, and immunological properties. Average counts for lactobacilli and Streptococcus thermophilus were greater than 10 million colony forming units per milliliter, indicating the capacity to provide a health benefit. Cashewgurt pH and viscosity values were comparable to cow milk yogurts, and it was off white in color. SDS-PAGE analysis indicated a clear reduction in Ana o 1 and 2, and immuno-assay with polyclonal anti-cashew IgG antibody and cashew-allergic IgE indicated an overall reduction in allergen content. In contrast, SDS-PAGE, mass spectrometry, immunoblot, and ELISA all revealed that Ana o 3 was relatively unaffected by the fermentation process. In conclusion, Ana o 1 and Ana o 2 are sensitive to degradation, while Ana o 3 survives lactic acid bacterial fermentation during yogurt production. The analysis presented here indicates that cashew nut yogurt is not suitable for those with cashew nut allergy.

Introduction: HyQvia (Immune Globulin Infusion 10% [Human] with Recombinant Human Hyaluronidase) was developed to combine the advantages of intravenous and subcutaneous immune globulin (SCIG), allowing administration of larger volumes at a single subcutaneous site with less frequent dosing when compared to other SCIG products. Current US prescribing guidelines for HyQvia are limited to adults and do not encompass the flexibility required to achieve success in all patients with primary immunodeficiency (PID)., Methods: This retrospective study was designed to evaluate the clinical experience of treating patients with PID with HyQvia regimens outside of package insert recommendations as well as in pediatric patients. Data were abstracted from 38 patient records (317 HyQvia infusions), including five patients less than 16 years of age, from seven US immunology clinics., Results: Among 37 patients receiving HyQvia regimens differing from prescribing guidelines, the most notable variations included shorter ramp-up periods, use of two rather than one infusion site, and slower than maximal infusion rates to mitigate local adverse events (AEs). The medication volume infused for single site doses ranged from 75 to 200 mL and doses split between two sites ranged from 100 to 750 mL. The most common type of regimen variation was a condensed ramp-up phase (shorter schedule, higher doses), and 96% (24/25) of patients managed in this way completed ramp-up. The most common ramp-up schedule was three infusions (one at 25-45%, another at 50-75%, and the final at 100% of target dose) spread over 2-4 weeks., Conclusions: A shorter ramp-up schedule did not appear to increase the number of AEs compared to standard ramp-up schedules. For patients with AEs, slower infusion rates and the use of two sites may improve medication tolerability. Four of five pediatric patients reported no AEs, and only one discontinued, stating a fear of needles. HyQvia may be tailored to adults requiring alternative rates, ramp-up, and/or dosing regimens and may be especially well-suited to children.

Humoral immunodeficiency patients require immunoglobulin replacement to prevent infection. Traditional intravenous immunoglobulin manufacturing methods have had the potential for containing impurities caused by physical, chemical and thermal stressors that alter proteins. Two intravenous immunoglobulin products, BIVIGAM ® and ASCENIV™, are manufactured by a modified Cohn-Oncley fractionation method followed by chromatographic purification. These products have undergone a systematic quality by design optimization to identify critical manufacturing processes to produce the highest quality product. This data driven, small-scale approach has led to manufacturing enhancements that have yielded consistent product improvements. The systematic approach to optimizing manufacturing has guided process changes, in-process, procedural and engineering controls that have reduced protein shearing and aggregation, and improved purity resulting in products with lot-to-lot consistency.

Immunoglobulin replacement therapy is the cornerstone of management for most primary immunodeficiency disease patients. The selection of a particular product, dose, and route of administration requires an understanding of the features of therapeutic immunoglobulin as well as patient-specific risk factors in order to maximize efficacy and tolerability and minimize risk. Individualizing therapy, taking into consideration the burdens of care, is necessary in order to optimize patient outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Peanut allergy (PA) is a significant and increasing problem, interfering with psychological development and family life. The standard recommendation to avoid peanut products and have access to injectable epinephrine is often inadequate. Oral immunotherapy for PA has been formally studied. Clinical observations of allergen immunotherapy have repeatedly enhanced patient care., Objective: The purpose of this study was to report observations on the treatment of 270 patients with PA over 8.5 years., Methods: This is a retrospective record review of patients beginning peanut oral immunotherapy between January 1, 2009, and June 1, 2017, approved by the North Texas Institutional Review Board., Results: A total of 270 patients aged 4 to 18 years comprising 107 girls and 163 boys were treated. A total of 214 of 270 patients (79%) completed immunotherapy escalation. Age (P < .001) and peanut IgE (P < .001) correlate inversely with completing dose escalation. Epinephrine-treated reactions in 63 and isolated gastrointestinal symptoms in 101 patients, respectively, were the most common adverse reactions to treatment but did not preclude success. Peanut IgE decreased by 65% after 3 years of maintenance treatment and 14 of 214 patients (6.5%) were able to achieve sustained unresponsiveness., Conclusions: In an allergy office practice setting, 79% of patients are able to complete a peanut desensitization protocol and maintain the desensitized state indefinitely with daily dosing. With appropriate planning and precautions, peanut oral immunotherapy may be performed in an allergy office. Careful observations of clinical treatment can contribute to the development of effective treatment strategies., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Many patients with primary immunodeficiency (PID) require immunoglobulin G (IgG) replacement therapy, delivered as intravenous IgG (IVIG) or subcutaneous IgG (SCIG). We aim to identify trends in efficacy and safety that would not be evident in individual studies of small patient numbers. Seven open-label, Phase 3, prospective, multicenter studies of the efficacy and safety of Hizentra® (a SCIG), conducted in Japan, Europe, and the US were summarized. Overall, 125 unique patients received 15,013 weekly infusions during a total observation period of 250.9 patient-years. Mean weekly doses of Hizentra® were 83.22-221.3 mg/kg body weight; infusion rates per patient (total body rate) were 25.2-49.3 mL/h across studies. The rates of infections and serious bacterial infections were 3.10 and 0.03 events per patient/year, respectively. Annualized rates of days hospitalized due to infection, out of work/school, and prophylactic antibiotic use were 0.95, 5.14, and 36.78 per patient, respectively. For the equivalent monthly dose, weekly Hizentra® SCIG administration resulted in expectedly-increased serum IgG trough levels in patients switching from IVIG, and maintained levels in patients switching from previous SCIG. Adverse events (AEs) totaled 5039 (events/infusion 0.094-0.773), almost all of which were mild/moderate. Three thousand one hundred ninety-seven were considered treatment-related, the most common of which were injection site reactions (2919 events; 0.001-0.592 AEs per infusion). Systemic AEs were very uncommon. The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment. This is particularly important in patients with PID, who may require lifelong IgG replacement therapy.

Genetic testing plays a critical role in diagnosis for many primary immunodeficiency diseases. The goals of this report are to outline some of the challenges that clinical immunologists face routinely in the use of genetic testing for patient care. In addition, we provide a review of the types of genetic testing used in the diagnosis of PID, including their strengths and limitations. We describe the strengths and limitations of different genetic testing approaches for specific clinical contexts that raise concern for specific PID disorders in light of the challenges reported by the clinical immunologist members of the CIS in a recent membership survey. Finally, we delineate the CIS's recommendations for the use of genetic testing in light of these issues.

Introduction: Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects. Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients. Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD). This product offers potential advantages over other available IG's for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition. In addition to its enhanced neutralizing anti-RSV activity and its polyclonal IG composition, there is preclinical data to support the use of RI-002 for humoral protection against other respiratory pathogens.