Hereditary angioedema outcomes in US patients switched from injectable long-term prophylactic medication to oral berotralstat.

BACKGROUND: Berotralstat, a first-line, once-daily, oral plasma kallikrein inhibitor for long-term prophylaxis of hereditary angioedema (HAE), is an effective and well-tolerated treatment option. OBJECTIVE: To summarize the safety, effectiveness, and impact on treatment satisfaction in patients who switched from injectable long-term prophylactics to oral berotralstat monotherapy (150 mg daily) at US sites in the international open-label APeX-S study. METHODS: APeX-S was an open-label, Phase II study of berotralstat conducted in 22 countries. Here, we focus on APeX-S patients enrolled at US sites who switched from injectable long-term prophylactics to berotralstat 150 mg once-daily monotherapy. RESULTS: A total of 34 patients discontinued lanadelumab (n = 21), subcutaneous C1 esterase inhibitor (n = 11), or intravenous C1 esterase inhibitor (n = 2) and switched to berotralstat 150 mg monotherapy. Vomiting, diarrhea, and upper respiratory tract infection were the most common adverse events (each 11.8%). Mean monthly attack rates were consistently low after the switch to berotralstat. The mean (SEM) monthly attack rate was 0.29 (0.11) at Month 1, 0.48 (0.15) at Month 6, and 0.58 (0.23) at Month 12. The median attack rate was 0 attack/mo throughout 12 months of treatment. Improvements were observed in the Treatment Satisfaction Questionnaire for Medication from baseline to Month 12 after the switch to berotralstat monotherapy, with the greatest improvements in convenience. CONCLUSION: The transition from injectable prophylactic medication to berotralstat was generally well tolerated. Patients switching to berotralstat monotherapy maintained good control of their HAE symptoms and reported improved treatment satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03472040.

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.

Contextual community epinephrine prescribing: Is more always better?

OBJECTIVE: Prompt administration of epinephrine is first-line management of anaphylaxis. Although severe anaphylaxis may require more than 1 epinephrine dose, multiple epinephrine device packs may not be necessary for all patients at risk for allergic reactions. DATA SOURCES: A narrative review was used to describe key considerations to contextualize community epinephrine prescribing. RESULTS: Anaphylaxis has a lifetime prevalence of 1.6% to 5.1%. Meeting diagnostic criteria for anaphylaxis is not required for epinephrine treatment of a severe allergic reaction. A "1-2-3" approach to anaphylaxis treatment is important to clearly relay central management steps: promptly administer a first dose of intramuscular epinephrine with proper positioning, and activate emergency medical services if immediate symptom resolution does not occur; consider a second dose of intramuscular epinephrine with consideration of oxygen administration and intravenous fluid if initial epinephrine response is not adequate; and consider a third intramuscular epinephrine dose together with consideration of intravenous fluid support and oxygen for continued lack of appropriate response. Although multiple epinephrine doses may be required to treat severe anaphylaxis, 90% of anaphylaxis cases do not require more than 1 epinephrine dose. A universal requirement for multiple epinephrine devices in patients without a history of anaphylaxis is not cost-effective. Patients without a history of anaphylaxis may be managed without multiple device prescriptions within a patient-preference sensitive paradigm of care. CONCLUSION: Anaphylaxis prevention involves appropriate education to avoid allergen triggers, recognize symptoms of an allergic reaction, rapidly access and administer intramuscular epinephrine, and appropriately activate emergency medical services when needed. For patients with previous anaphylaxis, particularly those who have required more than 1 dose of epinephrine to treat an allergic reaction, possessing multiple epinephrine devices is an important part of managing community anaphylaxis risk.

Postoperative Polyp Scale (POPS): Development of a New Sinonasal Polyp Grading Scale.

OBJECTIVE: Commonly used endoscopic grading scales, such as the nasal polyp scale, inadequately describe the degree of polyposis found postoperatively in the paranasal sinus cavities. The purpose of this study was to create a novel grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities, the Postoperative Polyp Scale (POPS). METHODS: A modified Delphi method was utilized to establish the POPS using consensus opinion among 13 general otolaryngologists, rhinologists, and allergists. Postoperative endoscopy videos from 50 patients with chronic rhinosinusitis with nasal polyps were reviewed by 7 fellowship-trained rhinologists and scored according to the POPS. Videos were rated again 1 month later by the same reviewers, and scores were assessed for test-retest and inter-rater reliability. RESULTS: Overall inter-rater reliability for the first and second reviews of the 52 videos was Kf = 0.49 (95% CI 0.42-0.57) and Kf = 0.50 (95% CI 0.42-0.57) for the POPS. Intra-rater reliability showed near-perfect test-retest reliability for the POPS with Kf = 0.80 (95% CI 0.76-0.84). CONCLUSION: The POPS is an easy-to-use, reliable, and novel objective endoscopic grading scale that more accurately describes polyp recurrence in the postoperative state which will be useful in the future for measuring the efficacy of various medical and surgical interventions. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:2885-2890, 2023.

Incidence of anaphylaxis and accidental peanut exposure: A systematic review.

BACKGROUND: Peanut allergy (PA), a common food allergy, is increasing in prevalence and is associated with high rates of anaphylaxis. Prevalence of food-related anaphylaxis is higher in children and adolescents than in adults, and the pediatric incidence is increasing. We conducted a systematic literature review and meta-analysis to determine the incidence of peanut-induced anaphylaxis in children and/or adolescents with PA. METHODS: Literature searches were conducted using the PubMed database and through supplemental methods. Eligible articles for inclusion were peer-reviewed studies published in English that reported the incidence of anaphylaxis in pediatric PA using the 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network criteria, sample size, and follow-up duration. Incidence rates were calculated as person-years at risk or a crude incidence rate was calculated. Meta-analyses of pooled data were conducted using the I2 statistic as the measure of heterogeneity. RESULTS: A total of 830 citations were screened; 8 met the study inclusion criteria and were selected for review. Pooled meta-analysis estimates of the incidence of (1) anaphylaxis among children/adolescents with food allergies, (2) anaphylaxis among children/adolescents with PA, and (3) accidental exposure to peanuts among children/adolescents with PA were 3.72 cases per 100 person-years (95% confidence interval [CI] = 2.35, 5.10), 2.74 cases per 100 person-years (95% CI = 1.42, 4.05), and 12.28 cases per 100 person-years (95% CI = 11.51, 13.05), respectively. CONCLUSIONS: The risks of anaphylaxis among children with food allergies and those with PA contribute to the serious overall burden of PA and food allergy for children and their families.

Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications.

Botulinum neurotoxins (BoNTs) are proteins produced by bacteria of the Clostridium family. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism. There are seven serotypes of BoNT (serotypes A-G); BoNT-A and BoNT-B are the botulinum toxin serotypes utilized for therapeutic applications. Treatment with BoNT injections is used to manage chronic medical conditions across multiple indications. As with other biologic drugs, immunogenicity after long-term treatment with BoNT formulations may occur, and repeated use can elicit antibody formation leading to clinical nonresponsiveness. Thus, approaching BoNT treatment of chronic conditions with therapeutic formulations that minimize stimulating the host immune response while balancing patient responsiveness to therapy is ideal. Immunogenicity is a clinical limitation in many settings that use biologic drugs for treatment, and clinically relevant immunogenicity reduction has been achieved through engineering smaller protein constructs and reducing unnecessary formulation components. A similar approach has influenced the evolution of BoNT formulations. Three BoNT-A products and one BoNT-B product have been approved by the Food and Drug Administration (FDA) for therapeutic use: onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB; a fourth BoNT-A product, daxibotulinumtoxinA, is currently under regulatory review. Additionally, prabotulinumtoxinA is a BoNT-A product that has been approved for aesthetic indications but not therapeutic use. Here, we discuss the preclinical and clinical immunogenicity data that exist within the scientific literature and provide a perspective for considering immunogenicity as a key factor in choice of BoNT formulation.

Characteristics of Peanut Allergy Diagnosis in a US Health Care Claims Database (2011-2017).

BACKGROUND: Peanut allergy is the most common food allergy among children. Studies assessing the burden of peanut allergy in a real-world setting are limited. OBJECTIVE: To estimate annual incidence and prevalence of peanut allergy cases among children aged 4 to 17 years and assess severe reaction and associated health care utilization rates. METHODS: Patient longitudinal data between January 2011 and December 2017 from a geographically and payer-type representative US health care claims database were used. Peanut allergy cases were identified using diagnostic codes and/or services indicating peanut-allergy-associated severe reactions/anaphylaxis. Estimated annual incidence was defined as peanut-allergic births as a proportion of all 1-year-olds and adjusted for less than 100% data set capture, undercoding, patient underpresenting rates, and spontaneous outgrowth. Prevalence was calculated on the basis of incidence. To assess rates of severe reactions to peanut and associated health care utilization, the cohort of 720,490 peanut allergy cases identified in 2011 was evaluated over a 6-year period from 2011 to 2017. RESULTS: Annual incidence increased from 1.7% to 5.2% between 2001 and 2017. Estimated prevalence in 4- to 17-year-olds was 1.25 million (2.2%) in 2017. Atopic comorbidities (asthma, 60.8%; atopic dermatitis, 61.7%) and other food allergies (35.3%) were common. Severe reactions (≥1) were observed in more than half (n = 399,806) the patients, and 37.9% were triggered by an accidental exposure. One in 5 patients (n = 144,883) visited the emergency department due to peanut exposure. CONCLUSIONS: Claims data suggest that the incidence and prevalence of peanut allergy in the United States may be increasing. Estimated severe reaction rates and health care utilization were high, suggesting that the burden of peanut allergy may be considerable.

Current trends in food allergy-induced anaphylaxis management at school.

OBJECTIVE: To review the evidence and current policies regarding the use of epinephrine at schools and child care centers DATA SOURCES AND STUDY SELECTIONS: A narrative review was performed based on the result of conference proceedings of a group of interprofessional stakeholders who attended the USAnaphylaxis Summit 2017 presented by Allergy & Asthma Network. RESULTS: Anaphylaxis is a well-recognized medical emergency that requires prompt treatment with intramuscular epinephrine. Anaphylaxis can be associated with poor quality of life. There is renewed recent focus on anaphylaxis management in schools. This interest has been spurred by an increase in the number of children with food allergy who are attending school, data that support up to 25% of first-time anaphylactic events occurring on school grounds, and a well-publicized fatality that helped to initiate a movement for stock, undesignated, non-student-specific epinephrine. Stock epinephrine is now available in 49 states, with an increasing number of states instituting mandatory reporting for use of such devices. Nursing efforts are paramount to support and implement stock epinephrine programs. Many states do not have clarity on delegation of authority for who can administer stock epinephrine, and there is evidence of variability in storage of stock devices. Few states have outcomes data that support successful implementation of stock epinephrine programs. CONCLUSION: Additional data are needed to demonstrate successful implementations of stock epinephrine programs and their outcomes. Such programs should include support for school nursing and clearer delineation of authority for medication administration as well as standards for where and how devices are stored.

Effect of a mobile health, sensor-driven asthma management platform on asthma control.

BACKGROUND: Asthma inflicts a significant health and economic burden in the United States. Self-management approaches to monitoring and treatment can be burdensome for patients. OBJECTIVE: To assess the effect of a digital health management program on asthma outcomes. METHODS: Residents of Louisville, Kentucky, with asthma were enrolled in a single-arm pilot study. Participants received electronic inhaler sensors that tracked the time, frequency, and location of short-acting ß-agonist (SABA) use. After a 30-day baseline period during which reference medication use was recorded by the sensors, participants received access to a digital health intervention designed to enhance self-management. Changes in outcomes, including mean daily SABA use, symptom-free days, and asthma control status, were compared among the initial 30-day baseline period and all subsequent months of the intervention using mixed-model logistic regressions and χ2 tests. RESULTS: The mean number of SABA events per participant per day was 0.44 during the control period and 0.27 after the first month of the intervention, a 39% reduction. The percentage of symptom-free days was 77% during the baseline period and 86% after the first month, a 12% improvement. Improvement was observed throughout the study; each intervention month demonstrated significantly lower SABA use and higher symptom-free days than the baseline month (P < .001). Sixty-nine percent had well-controlled asthma during the baseline period, 67% during the first month of the intervention. Each intervention month demonstrated significantly higher percentages than the baseline month (P < .001), except for month 1 (P = .80). CONCLUSION: A digital health asthma management intervention demonstrated significant reductions in SABA use, increased number of symptom-free days, and improvements in asthma control. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02162576.

Comparison of systemic reactions in rush, cluster, and standard-build aeroallergen immunotherapy.

BACKGROUND: Given the choice of standard, cluster, and rush build-up for aeroallergen immunotherapy, standard-build immunotherapy has generally been preferred because of a perceived high rate of systemic reactions (SRs) associated with cluster and rush immunotherapy. OBJECTIVE: To characterize the incidence of SRs during standard, cluster, and rush build-up immunotherapy in an allergy practice during a 5-year period. METHODS: A retrospective review was conducted among patients receiving standard-build, 8- to 10-step cluster, or 2-day rush immunotherapy from January 1, 2010, through December 31, 2014, at Family Allergy & Asthma clinics in Louisville, Kentucky. Investigators excluded reactions that occurred during skin prick testing, venom immunotherapy, and not-true SRs, and identified the build-up method, age, sex, date of reaction, vial concentration, and presence of asthma. Per-shot and per-patient incidence of SRs was computed from these data. RESULTS: During our review period, 2,549,643 injections were administered to 11,982 patients. Per-shot incidence of SR was 0.01%, 0.06%, and 0.33% for standard, cluster, and rush immunotherapy, respectively; per-patient incidence of SR was 2.84%, 2.52%, and 11.86% for standard, cluster, and rush immunotherapy, respectively. A total of 42% of SRs were grade 1, 43% were grade 2, 12% were grade 3, and 3% were grade 4. No fatalities were reported. A total of 70% of total SRs, 75% of cluster SR, and 55% of rush SR occurred in females, with an emergent peak in SR from May to October. CONCLUSION: Compared with previously published rates, we observed a decrease in the incidence of SR for standard, cluster, and rush immunotherapy, with peak seasonality from May to October and a female predominance.

Addressing barriers to emergency anaphylaxis care: from emergency medical services to emergency department to outpatient follow-up.

BACKGROUND: Anaphylaxis is a systemic life-threatening allergic reaction that presents unique challenges for emergency care practitioners. Allergists and emergency physicians have a history of collaborating to promote an evidence-based, multidisciplinary approach to improve the emergency management and follow-up of patients with or at risk of anaphylaxis. OBJECTIVES: To review recent scientific literature about anaphylaxis, discuss barriers to care, and recommend strategies to support improvement in emergency anaphylaxis care. METHODS: An expert panel of allergists and emergency physicians was convened by the American College of Allergy, Asthma and Immunology in November 2014 to discuss current knowledge about anaphylaxis, identify opportunities for emergency practitioners and allergists to partner to address barriers to care, and recommend strategies to improve medical management of anaphylaxis along the continuum of care: from emergency medical systems and emergency department practitioners for acute management through appropriate outpatient follow-up with allergists to confirm diagnosis, identify triggers, and plan long-term care. RESULTS: The panel identified key barriers to anaphylaxis care, including difficulties in making an accurate diagnosis, low rates of epinephrine administration during acute management, and inadequate follow-up. Strategies to overcome these barriers were discussed and recommendations made for future allergist/emergency physician collaborations, and key messages to be communicated to emergency practitioners were proposed. CONCLUSION: The panel recommended that allergists and emergency physicians continue to work in partnership, that allergists be proactive in outreach to emergency care practitioners, and that easy-to-access educational programs and materials be developed for use by emergency medical systems and emergency department practitioners in the training environment and in practice.

Occupational rhinitis.

Work-related rhinitis, which includes work-exacerbated rhinitis and occupational rhinoconjunctivitis (OR), is two to three times more common than occupational asthma. High molecular weight proteins and low molecular weight chemicals have been implicated as causes of OR. The diagnosis of work-related rhinitis is established based on occupational history and documentation of immunoglobulin E (IgE) mediated sensitization to the causative agent if possible. Management of work-related rhinitis is similar to that of other causes of rhinitis and includes elimination or reduction of exposure to causative agents combined with pharmacotherapy. If allergens are commercially available, allergen immunotherapy can be considered.

Seminal plasma hypersensitivity reactions: an updated review.

Seminal plasma hypersensitivity manifests as a spectrum of systemic and/or localized clinical symptoms after exposure to specific protein components in seminal fluid. The prevalence of this disease is largely unknown, but it is believed to affect up to 40,000 women in the United States. Although no definitive risk factors have been confirmed, women with systemic reactions are frequently atopic. Prostate-specific antigen is believed to be the major allergen involved in the disorder, but other proteins are likely involved. Interestingly, up to 40%-50% of both systemic and localized seminal plasma hypersensitivity cases can occur after first-time intercourse. Diagnosis is based on clinical history. The gold standard for diagnosing seminal plasma hypersensitivity is prevention of symptoms with the use of a condom. Patients with seminal plasma hypersensitivity demonstrate positive prick skin test and/or serum-specific immunoglobulin E to whole seminal fluid or fractionated seminal plasma proteins. Treatment of seminal plasma hypersensitivity involves either avoidance with the use of condoms, intravaginal graded challenge using dilutions of whole seminal fluid, or subcutaneous desensitization to relevant fractionated seminal plasma proteins obtained from the woman's sexual partner. In most cases, treatment using one or more of the above approaches has been very successful. Infertility has not been demonstrated to be directly related to seminal plasma hypersensitivity, although women with the condition frequently have difficulty conceiving due to their inability to have unprotected sexual intercourse.

Characterization of patients with suspected seminal plasma hypersensitivity.

The epidemiology of seminal plasma hypersensitivity (SPH) is unknown. Case reports and a previous survey have identified two distinct phenotypes: localized and systemic reactors. The objective of this study was to use an Internet-based questionnaire to characterize and examine the differences among a population of women with suspected SPH. A questionnaire designed to distinguish women with probable SPH was made available via the Internet. Systemic symptoms included generalized pruritus, urticaria, angioedema, wheezing, chest tightness, shortness of breath, dizziness, and loss of consciousness whereas localized symptoms included vaginal burning, pain, swelling, erythema, or blister formation. Respondents with localized or systemic symptoms and whose symptoms were prevented with the use of a condom were included in the analysis. Frequency and means were calculated and further analyzed using chi-square and t-test analyses. A total of 165 women with probable SPH, 79 with systemic symptoms and 86 with only localized symptoms, were included in the analysis. Systemic compared with localized respondents were significantly older (mean age, 29.2 years versus 26.4 years; p = 0.01), had longer duration of symptoms (mean, 58 months versus 40.8 months; p = 0.03), and more frequently reported a family history of atopy (65.8% versus 50%; p < 0.05). Interestingly, significantly more systemic compared with localized respondents reported dog sensitization (11.4% versus 2.3%; p = 0.02). Localized and systemic SPH are more common than previously realized and should be considered in the differential diagnosis of anaphylaxis, vulvovaginitis, and dyspareunia. Additional research investigating the epidemiology, immunopathogenesis, and treatment of this disorder is warranted.

Occupational rhinitis.

Work-related rhinitis, which includes work-exacerbated rhinitis and occupational rhinitis, may be two to three times more common than occupational asthma. Both high molecular weight proteins and low molecular weight chemicals have been implicated as causes of occupational rhinitis. A diagnosis is established based on occupational history and, if appropriate, documentation of IgE-mediated sensitization to the causative agent. Management of work-related rhinitis is similar to that of non-work-related rhinitis and includes elimination or reduction of exposure to offending agents combined with pharmacotherapy. If treatment allergens are commercially available, allergen immunotherapy may also be considered if appropriate.