Epicutaneous immunotherapy with Viaskin™ Peanut in toddlers: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article published in The New England Journal of Medicine about the EPITOPE clinical study, which tested a skin patch called ViaskinTM Peanut 250 µg (micrograms) as a treatment option for peanut allergy in children aged 1 through 3 years. The patch is a form of epicutaneous immunotherapy (EPIT), which is a new approach to allergen immunotherapy that delivers a small amount of peanut protein to the immune system through the skin. Viaskin Peanut is an investigational therapy, meaning it has not yet been approved by the United States Food and Drug Administration (FDA), that has been studied before in young children aged 4 through 11 years. In those studies, the children who received the patch were desensitized and were less likely to experience anaphylaxis when they ate peanut at the end of the study. The EPITOPE study included children aged 1 through 3 years with peanut allergy and looked at how well the peanut patch worked and how safe it was compared to a patch with no medicine (placebo, no medicine) after 12 months. WHAT WERE THE KEY TAKEAWAYS?: The study showed that the peanut patch was better in desensitizing children to peanuts than the placebo patch. Most of the children in the study who received the peanut patch for 12 months (the treatment group) were able to eat and tolerate more peanut at the end of the study than those who received only the placebo patch (the control group). This demonstrates that the children in the treatment group were less likely to have an allergic reaction if they ate peanut by accident at the end of the study. The children in the treatment group also had less severe symptoms when they were given peanut during the oral food challenges at the end of the study. Most children in both groups experienced side effects. Mild to moderate local skin reactions where the patch was applied were most common. These side effects happened less often and were less serious over the 12-month treatment period. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Overall, these results show the peanut patch may be a possible treatment option to help desensitize young children with peanut allergy to peanut.

Innovations in the treatment of anaphylaxis: A review of recent data.

PURPOSE OF REVIEW: The current standard of first-line emergency treatment of anaphylaxis is intramuscular (IM) epinephrine, mostly administered through epinephrine autoinjector (EAI) in the outpatient setting. However, undercarriage and underuse of EAIs are common, and delayed epinephrine use is associated with increased morbidity and mortality. Patients, caregivers, and healthcare professionals have expressed a strong desire for small, needle-free devices and products that would offer improved carriage, ease of use, and more convenient, less invasive routes of epinephrine administration. Novel mechanisms of epinephrine administration are under investigation to help address several recognized EAI limitations. This review explores innovative nasal and oral products under investigation for the outpatient emergency treatment of anaphylaxis. FINDINGS: Human studies of epinephrine administered through nasal epinephrine spray, a nasal powder spray, and a sublingual film have been conducted. Data from these studies indicate promising pharmacokinetic results comparable to those of the standard of outpatient emergency care (0.3-mg EAI) and syringe and needle IM epinephrine administration. Several products have shown maximum plasma concentration values higher than those of the 0.3-mg EAI and manual IM injection, although it remains unclear whether this has clinical relevancy in patient outcomes. Generally, these modalities show comparable time to maximum concentrations. Pharmacodynamic changes observed with these products are comparable to or more robust than those seen with EAI and manual IM injection. SUMMARY: Given comparable or superior pharmacokinetic and pharmacodynamic results and safety of innovative epinephrine therapies to those of current standards of care, US Food and Drug Administration approval of these products may help address numerous barriers that EAIs present. The ease of use and carriage and favorable safety profiles of needle-free treatments may make them an attractive alternative to patients and caregivers, potentially addressing injection fears, needle-based safety risks, and other reasons for lack of or delayed use.

Development of a novel shared decision making aid for primary immunodeficiency diseases.

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.

Shared decision making and developing a decision aid Shared decision making happens when patients and doctors work together to choose treatment options based on a patient's concerns, preferences, goals and values, as well as medical information. The aim of this project was to develop a decision aid to help patients with primary immunodeficiency diseases (PID), in which part of the body's immune system is missing or doesn't function correctly. This will allow patients to better understand and communicate with the healthcare team on their preferences about immunoglobulin treatments, which fight infection by boosting antibody (protein) levels in the blood. The authors talked to experts and reviewed existing information to decide what treatment features the aid should consider. Patients with PID then tested the aid, and changes were made based on their feedback. Doctors specializing in treating PID also provided their feedback. The final aid was judged to be helpful and easy to use by the participants. With further research, this aid could be used to help inexperienced patients better understand what immunoglobulin treatment features are most important to them, and support shared decision-making between patients and their doctors.

A Registry Study of 240 Patients with X-Linked Agammaglobulinemia Living in the USA.

PURPOSE: To understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry. METHODS: The USIDNET registry was queried for data from XLA patients collected from 1981 to 2019. Data fields included demographics, clinical features before and after diagnosis of XLA, family history, genetic mutation in Bruton's tyrosine kinase (BTK), laboratory findings, treatment modalities, and mortality. RESULTS: Data compiled through the USIDNET registry on 240 patients were analyzed. Patient year of birth ranged from 1945 to 2017. Living status was available for 178 patients; 158/178 (88.8%) were alive. Race was reported for 204 patients as follows: White, 148 (72.5%); Black/African American, 23 (11.2%); Hispanic, 20 (9.8%); Asian or Pacific Islander, 6 (2.9%), and other or more than one race, 7 (3.4%). The median age at last entry, age at disease onset, age at diagnosis, and length of time with XLA diagnosis was 15 [range (r) = 1-52 years], 0.8 [r = birth-22.3 years], 2 [r = birth-29 years], and 10 [r = 1-56 years] years respectively. One hundred and forty-one patients (58.7%) were < 18 years of age. Two hundred and twenty-one (92%) patients were receiving IgG replacement (IgGR), 58 (24%) were on prophylactic antibiotics, and 19 (7.9%) were on immunomodulatory drugs. Eighty-six (35.9%) patients had undergone surgical procedures, two had undergone hematopoietic cell transplantation, and two required liver transplantation. The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. Bacteremia/sepsis and meningitis were reported more frequently before XLA diagnosis while encephalitis was more commonly reported after diagnosis. Twenty patients had died (11.2%). The median age of death was 21 years (range = 3-56.7 years). Neurologic condition was the most common underlying co-morbidity for those XLA patients who died. CONCLUSIONS: Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. With improved life expectancy, more efforts will be required to improve post-diagnosis organ dysfunction and quality of life. Neurologic manifestations are an important co-morbidity associated with mortality and not yet clearly fully understood.

Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience.

BACKGROUND: ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein. OBJECTIVE: To determine the real-life long-term benefits of REVCOVI in ADA-SCID. METHODS: Data on ERT, infectious and noninfectious complications, and metabolic and immune evaluations were collected from 17 patients with ADA-SCID treated for 6 months or more with REVCOVI. RESULTS: Eleven patients had previously received ADAGEN for 16 to 324 months, whereas 6 patients were ERT-naive. REVCOVI was administered twice weekly at 0.4 mg/kg/wk in ERT-naive patients, whereas patients transitioning to REVCOVI from ADAGEN typically continued at the same frequency and equivalent dosing as ADAGEN, resulting in a significantly lower (P = .007) total REVCOVI dose in the transitioning group. REVCOVI treatment in the ERT-naive group led to the resolution of many clinical and laboratory complications of ADA deficiency, whereas there were no new adverse effects among the transitioning patients. REVCOVI treatment increased plasma ADA activity and decreased dAXP (which included deoxyadenosine mono-, di-, and tri phosphate) among most patients, effects that persisted throughout the 7- to 37-month treatment periods, except in 2 patients with incomplete adherence. Among some patients, after 0.5 to 6 months, injection frequency was reduced to once a week, while maintaining adequate metabolic profiles. All ERT-naive infants treated with REVCOVI demonstrated an increase in the number of CD4+ T and CD19+ B cells, although these counts remained stable but lower than normal in most transitioning patients. CONCLUSIONS: REVCOVI is effective for the management of ADA-SCID.

Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development.

Current practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) and coloboma, heart defect, atresia choanae, retardation of growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome. Practice variations affect the initial and subsequent assessment of immune function, the terminology used to describe the condition and immune status, the accepted criteria for recommending live vaccines, and how often follow-up is needed based on the degree of immune compromise. The lack of consensus and widely varying practices highlight the need to establish updated immunological clinical practice guidelines. These guideline recommendations provide a comprehensive review for immunologists and other clinicians who manage immune aspects of this group of disorders.

Autoimmunity in Primary Immunodeficiencies (PID).

Primary immunodeficiency (PID) may impact any component of the immune system. The number of PID and immune dysregulation disorders is growing steadily with advancing genetic detection methods. These expansive recognition methods have changed the way we characterize PID. While PID were once characterized by their susceptibility to infection, the increase in genetic analysis has elucidated the intertwined relationship between PID and non-infectious manifestations including autoimmunity. The defects permitting opportunistic infections to take hold may also lead the way to the development of autoimmune disease. In some cases, it is the non-infectious complications that may be the presenting sign of PID autoimmune diseases, such as autoimmune cytopenia, enteropathy, endocrinopathies, and arthritis among others, have been reported in PID. While autoimmunity may occur with any PID, this review will look at certain immunodeficiencies most often associated with autoimmunity, as well as their diagnosis and management strategies.

Health-Related Quality of Life in 91 Patients with X-Linked Agammaglobulinemia.

PURPOSE: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency (PID) caused by a defect in the gene encoding for Bruton tyrosine kinase (BTK). In the absence of a functional BTK, patients have low or absent circulating B cells and low or absent serum immunoglobulin. Despite gammaglobulin replacement and prompt use of antimicrobial agents, patients with XLA continue to experience infectious and non-infectious complications throughout their lifetime. The purpose of this study was to understand self-perceived health status of US-based patients with XLA, and examine the associations amongst clinical characteristics, treatment experience, and quality of life (QoL). METHODS: A 46 and 68 question survey, developed by the Immune Deficiency Foundation (IDF) and a Short Form-12item v2® (SF-12v2®) for adults and SF-10™ for children to assess QoL, were mailed by IDF to patients in 2017 and 2018. Those that self-identified as having XLA or males with agammaglobulinemia were selected for analysis. Mean physical and mental composite scores (PCS and MCS) from SF-12v2® and mean physical health component (PHS) and psychological health summary (PSS) from SF-10™ scores were compared to the US normative data. RESULTS: Ninety-one patients completed the surveys: 58 (63.7%) adults and 33 (36.3%) children. For the combined surveys, the overall median age at time of the survey was 28.5 years (yrs); Inter-Quartile-Range (IQR) 13-49.5 yrs; the median age at diagnosis was 2 yrs (IQR = 0-4 yrs) and the median number of years with XLA diagnosis was 23 (IQR 10.75-40yrs). Amongst adult patients, physical scores were noted to be below the general adult population but did not reach statistical significance. In contrast, 2 or more chronic conditions impacted both physical and mental QoL (p < .001) and hospitalization was associated with significantly decreased physical health QoL (p < .001); three or more infections in the past 12 months exhibited impact on physical health although was not found to be statistically significant. Adult patients with public insurance fared worse in mental health domains compared to those with combined public and private or those with private alone (p = 0.001). Employment status did not impact QoL. None of these variables met statistical significance nor demonstrated impact within the pediatric population in either physical or mental domains of health. CONCLUSION: Our study provides further insight into what factors impact both physical and mental domains of health amongst patients with XLA. Early detection to prevent the development of associated morbidity, as well as vigilant care to prevent hospitalizations and infections, can limit the impact this disease may have on the overall well-being of XLA patients.

Spectrum of Genetic T-Cell Disorders from 22q11.2DS to CHARGE.

Improved genetic testing has led to recognition of a diverse group of disorders of inborn errors of immunity that present as primarily T-cell defects. These disorders present with variable degrees of immunodeficiency, autoimmunity, multiple organ system dysfunction, and neurocognitive defects. 22q11.2 deletion syndrome, commonly known as DiGeorge syndrome, represents the most common disorder on this spectrum. In most individuals, a 3 Mb deletion of 22q11 results in haploinsufficiency of 90 known genes and clinical complications of varying severity. These include cardiac, endocrine, gastrointestinal, renal, palatal, genitourinary, and neurocognitive anomalies. Multidisciplinary treatment also includes pediatrics/general practitioners, genetic counseling, surgery, interventional therapy, and psychology/psychiatry. Chromosome 10p deletion, TBX1 mutation, CHD7 mutation, Jacobsen syndrome, and FOXN1 deficiency manifest with similar overlapping clinical presentations and T-cell defects. Recognition of the underlying disorder and pathogenesis is essential for improved outcomes. Diagnosing and treating these heterogenous conditions are a challenge and rapidly improving with new diagnostic tools. Collectively, these disorders are an example of the complex penetrance and severity of genetic disorders, importance of translational diagnostics, and a guide for multidisciplinary treatment.

Peanut cross-contamination in randomly selected baked goods.

BACKGROUND: The current standard of care for managing peanut allergy includes avoidance of peanut and use of injectable epinephrine; however, strict avoidance is difficult and accidental ingestion is common with potentially serious consequences. Despite vigilance and efforts to minimize the risk of accidental exposure, peanut protein cross-contamination continues to occur in a variety of foods, including baked goods. OBJECTIVE: To assess and quantify the presence of peanut protein contamination in certain baked goods. METHODS: Randomly selected baked goods were collected from bakeries in the New York and Miami metropolitan areas that sold a variety of ethnic cuisines. A second set of samples from the same bakeries was collected at least 1 week after to evaluate between-batch variability. Samples were sent to the Food Allergy Research and Resource Program to analyze peanut contamination by enzyme-linked immunosorbent assay. Consumption estimates were based on 2003 to 2010 National Health and Nutrition Examination Survey survey data. RESULTS: Of 154 samples from 18 bakeries, 4 (2.6%) had detectable peanut contamination with peanut protein levels ranging from 0.1 mg/100 g to 650 mg/100 g. Consumption estimates for single occasion ingestion of a contaminated item ranged from 0.07 mg to 832 mg of peanut protein. CONCLUSION: In this study, unintended peanut protein was present in a small, but not insignificant, proportion of baked goods, with the potential to trigger a reaction in individuals with peanut allergy. Some products contained high levels of unintended peanut protein. The current data support the potential for accidental exposure to peanut protein with its associated risk.