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Although omalizumab is currently approved for a limited number of indications—such as asthma, chronic rhinosinusitis with nasal polyps, and chronic spontaneous urticaria—its potential applications are expanding each year. Owing to its diverse and not yet fully elucidated mechanism of action, including effects on both IgE- and non-IgE-mediated hypersensitivity reactions with delayed onset, this monoclonal antibody may be beneficial in a wide range of allergic and non-allergic conditions. To date, numerous clinical trials and case reports have documented the successful off-label use of omalizumab. It appears particularly promising for patients with difficult-to-treat hypersensitivities, such as food and drug allergies, which continue to pose significant challenges in modern allergology. Even though further research is needed to establish clear indications for its use in these contexts, omalizumab holds considerable potential to enhance the outcomes and clinical efficacy of food immunotherapy and drug desensitization protocols. The aim of this review is to present the current and potential future applications of omalizumab as an adjunctive treatment in food allergy therapy and in desensitization protocols for patients with hypersensitivity to selected drugs.

Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Antibiotic allergies are commonly reported among patients, but most do not experience reactions on rechallenge with the same agents. These reported allergies complicate management of infections in patients labelled as having penicillin allergy, including serious infections where penicillin-based antibiotics are the first-line (most effective and least toxic) treatment option. Allergy labels are rarely questioned in clinical practice, with many clinicians opting for inferior second-line antibiotics to avoid a perceived risk of allergy. Reported allergies thereby can have significant impacts on patients and public health, and present major ethical challenges. Antibiotic allergy testing has been described as a strategy to circumvent this dilemma, but it carries limitations that often make it less feasible in patients with acute infections or in community settings that lack access to allergy testing. This article provides an empirically informed ethical analysis of key considerations in this clinical dilemma, using Staphylococcus aureus bacteraemia in patients with penicillin allergies as a case study. We argue that prescribing first-line penicillin-based antibiotics to patients with reported allergies may often present a more favourable ratio of benefits to risks, and may therefore be more ethically appropriate than using second-line drugs. We recommend changes to policy-making, clinical research and medical education, in order to promote more ethically acceptable responses to antibiotic allergies than the status quo.

The use of acetylsalicylic acid (ASA) is problematic in subjects with histories of hypersensitivity reactions (HRs) to it or with cross-reactive types of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We sought to evaluate the efficacy of low-dose ASA challenge (LDAC) and desensitization to allow ASA therapy at an antiplatelet dose in patients with atherosclerotic cardiovascular disease (ASCVD) or multiple related risk factors and histories of HRs to ASA or ≥ 2 chemically unrelated NSAIDs. We studied prospectively all patients with such histories and ≥ 3 risk factors for ASCVD (group I), chronic coronary syndrome (CCS, group II), and acute coronary syndrome (ACS) with indication for ASA desensitization (group III). Patients from groups I and II underwent LDACs (cumulative dose of 110 mg), while those from group III were desensitized (cumulative dose of 100.1 mg). We evaluated 103 patients: 62 from group I, 24 from group II, and 17 from group III. Eighty-two of the 86 patients from the first two groups underwent LDACs and 2 reacted. Subsequently, 22 (27.5%) of the 80 patients with negative LDACs were administered dual antiplatelet therapy with ASA after successful percutaneous coronary interventions, thus sparing desensitizations. The remaining 4 patients with CCS and all 17 patients from group III were successfully desensitized. In this pragmatic study, LDAC proved to be a safe and reliable diagnostic tool for identifying patients with histories of HRs to ASA or ≥ 2 different NSAIDs who can tolerate ASA at antiplatelet doses. Routine LDAC is advisable in all patients at high risk for ASCVD or with CCS who report HRs to ASA or ≥ 2 NSAIDs. ASA desensitization remains a safe and effective option in patients with ACS.Study flow-chart.ASCVD atherosclerotic cardiovascular disease; CCS chronic coronary syndrome; ACS acute coronary syndrome; ASA acetylsalicylic acid; DAPT dual antiplatelet therapy; PCI percutaneous coronary intervention; NSAIDs nonsteroidal anti-inflammatory drugs; NERD NSAID-exacerbated respiratory disease; NECD NSAID-exacerbated cutaneous disease; NIUAA NSAID-induced urticaria-angioedema or anaphylaxis; SNIUAA single NSAID-induced urticaria-angioedema or anaphylaxis; SNIDHR single NSAID-induced delayed hypersensitivity reaction.

The off-label use of medicines is a common and extensive clinical practice. Omalizumab has been licensed for use in severe allergic asthma and chronic urticaria. Omalizumab dosing was based on body weight and baseline serum IgE concentration. All patients are required to have a baseline IgE between 30 and 700 IU/ml and body weight not more than 150 kg. The use of off-label drugs may lead to several problems including adverse effects and an increased risk/benefit balance. In this article, there are summarized off-label uses of omalizumab in the last recent years in diseases in which IgE maybe or certainly has a corner role such as allergic rhinitis, allergic bronchopulmonary aspergillosis, anaphylaxis, keratoconjunctivitis, food allergy, drug allergy, urticaria, angioedema, non-atopic asthma, atopic dermatitis, nasal polyps, Churg-Strauss syndrome, eosinophilic otitis media, chronic rhinosinusitis, bullous pemphigoid, contact dermatitis, and others. Use in pregnancy asthmatic women and pre-co-administration with specific immunotherapy will also be revised.

[Display omitted] •10–20% of patients receiving medical care have a penicillin allergy label in their chart.•However, less than 1% of all patients are truly allergic to penicillin.•Penicillin allergy labels increase costs, worsen outcomes and contribute to the global burden of antibiotic resistance.•A de-labeling approach should include careful history taking, allergy testing with an allergist and/or non-allergist provider

IntroductionPatient-reported antibiotic allergy labels (AALs) are common. These labels have been demonstrated to have a negative impact on use of appropriate antibiotics and patient-related health outcomes. These patients are more likely to receive suboptimal antibiotics, have increased rates of surgical site infections and are more likely to be colonised with multidrug-resistant organisms. Increasing recognition that antibiotic allergy forms a key part of good antimicrobial stewardship has led to calls for greater access to antibiotic allergy assessment.PREPARE is a pilot randomised controlled trial of beta-lactam allergy assessment and point of care delabelling in perioperative patients utilising a validated antibiotic allergy assessment tool that has been repurposed into a smartphone application. The aim of the study is to assess the feasibility and safety of this approach in the perioperative outpatient setting.Methods and analysisAdult participants requiring elective surgery and are likely to require prophylactic intravenous antibiotics will be recruited. During the intervention phase, participants will be randomised to the intervention or control arm, with control patients receiving usual standard of care. Those randomised to intervention undertake a risk assessment via the smartphone application, with those deemed low risk proceeding to direct oral provocation with either a penicillin or cephalosporin. Study outcomes will be evaluated in the postintervention phase, 30 and 90 days after surgery.Feasibility of intervention delivery and recruitment will be reported as proportions with respective 95% CIs. Participants who experience an antibiotic adverse event will be reported by group with respective 95% CIs and compared using modified Poisson regression model with robust SE estimation.Ethics and disseminationThis protocol has received approval from the Austin Health human research and ethics committee, Heidelberg, Victoria, Australia (HREC/17/Austin/575). Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences.Trial registration numberACTRN12620001295932.

IntroductionIodinated contrast media are commonly used in medical imaging and can cause hypersensitivity reactions, including rare but severe life-threatening reactions. Although several prophylactic approaches have been proposed for severe reactions, their effects remain unclear. Therefore, we aim to review systematically the preventive effects of pharmacologic and non-pharmacologic interventions and predictors of acute, hypersensitivity reactions.Methods and analysisWe will search the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases from 1 January 1990 through 31 December 2019 and will examine the bibliographies of eligible studies, pertinent review articles and clinical practice guidelines. We will include prospective and retrospective studies of any design that evaluated the effects of pharmacological and non-pharmacological preventive interventions for adverse reactions of non-ionic iodinated contrast media. Two assessors will independently extract the characteristics of the study and intervention and the quantitative results. Two independent reviewers will assess the risk of bias using standard design-specific validity assessment tools. The primary outcome will be reduction in acute contrast media-induced hypersensitivity reactions. The secondary outcomes will include characteristics associated with the development of contrast media-induced acute hypersensitivity reactions, and adverse events associated with specific preventive interventions. Unique premedication regimens (eg, dose, drug and duration) and non-pharmacological strategies will be analysed separately. Average-risk and high-risk patients will be considered separately. A meta-analysis will be performed if appropriate.Ethics and disseminationEthics approval is not applicable, as this will be a secondary analysis of publicly available data. The results of the analysis will be submitted for publication in a peer reviewed journal.PROSPERO registration numberCRD42019134003

Correspondence to Michael Wilcock, Pharmacy, Royal Cornwall Hospitals NHS Trust, Truro, UK; mike.wilcock@nhs.net Correcting (or delabelling) inaccurate penicillin allergy labels is an important component of antimicrobial stewardship.1 2 Over recent years, there has been greater recognition of the harms associated with having penicillin allergy wrongly noted in medical records, as well as development of tools to support delabelling initiatives.3 4 The proportion of incorrect penicillin allergy labels has been reported to be about 95% following subsequent testing.5 People who have a label of penicillin allergy are more likely to be treated with alternative antibacterials that have a broader spectrum of activity, which may impact on antimicrobial resistance patterns. [...]there is growing resistance to last-line antibiotics, which is associated with a higher risk of mortality disproportionately affecting deprived or non-white populations, and increasing resistance to alternative antibiotics in primary care.6 Delabelling penicillin allergy by non-allergists is supported by national and international guidelines.5 7 The British Society for Allergy and Clinical Immunology (BSACI) guideline includes a checklist to identify patients at low risk of allergy and a framework for drug provocation testing by non-allergists.5 A systematic review of 69 studies reporting on the successful delabelling of 5019 patients delivered by non-allergists provides further evidence for this intervention.8 In the review, the methods of delabelling included direct delabel (removal of allergy record on history alone), direct drug provocation testing (most often using a single dose of oral amoxicillin) and skin testing followed by direct drug provocation testing.8 These were delivered, mainly in inpatient settings, by pharmacists, doctors, nurses, physician associates, medical students and pharmacy students. [...]work is underway to provide evidence to support implementation of the BSACI guideline and this will be made available across health and social care services.9 Nevertheless, as others have argued, patients and clinicians will ‘need to be supported to use penicillin allergy services and be provided with the skills and information to prescribe and use penicillins appropriately after a negative test result.’10 Competing interests None declared.

Background Though 15% of hospitalized patients have a documented penicillin (PCN) allergy, fewer than 1% have an IgE-mediated reaction that necessitates avoidance of β-lactam antibiotics. Objective Our interdisciplinary team of medical and nursing students led and executed a two-pronged quality improvement intervention to reduce prescribing of non-β-lactam antibiotics (NBLs) for patients with reported PCN allergies. To the best of our knowledge, this is the first multidisciplinary student-led intervention aimed at educating providers on low-risk penicillin allergy and encouraging best antibiotic prescribing practices. Design and participants The intervention took place from June 2021 to February 2022. We developed and provided clinician education modules, including peer-to-peer information sharing and in-person small group discussions, as well as clinical decision support (CDS) strategies through the electronic medical record (EMR). The target population was attendings, residents, nurse practitioners, and physician assistants on the hospital medicine service at a large urban academic tertiary care center. We followed the SQUIRE 2.0 guidelines for reporting on quality improvement. Main measures Primary outcome measures included number of NBL prescriptions and use of nonspecific descriptors (e.g., “other” or “unknown”) for PCN allergy reaction type, and were compared with a pre-intervention period. Key results The percent of β-lactam prescriptions for patients with a PCN allergy after the intervention increased from 19 to 23% ( p  = 0.006). For patients with a low severity PCN allergy, the percent of β-lactam prescriptions increased from 20 to 28% ( p  = 0.001). There was a significant decrease in nonspecific PCN allergy reaction type from 23% in the pre-intervention period to 20% post-intervention ( p  = 0.012). Conclusions An intervention focused on educating prescribers and CDS strategies delivered through the EMR increased appropriate β-lactam prescribing for patients with a documented low-risk PCN allergy and reduced the use of nonspecific PCN allergy reaction type in EMR documentation.