Justin Greiwe’s research while affiliated with University of Cincinnati and other places

Background Limited decision‐support tools are available to help shared decision‐making (SDM) regarding food oral immunotherapy (OIT) initiation. No current tool covers all foods, forms, and pediatric ages for which OIT is offered. Methods In compliance with International Patient Decision Aid Standards criteria, this pediatric decision‐aid comparing OIT versus avoidance was developed in three stages. Nested qualitative data assessing OIT decisional needs were supplemented with evidence‐synthesis from the OIT literature to create the prototype decision‐aid content. This underwent iterative development with food allergy experts and patient advocacy stakeholders until unanimous consensus was reached regarding content, bias, readability, and utility in making a choice. Lastly, the tool underwent validated assessment of decisional acceptability, decisional conflict, and decisional self‐efficacy. Results The decision‐aid underwent 5 iterations, resulting in a 4‐page written aid (Flesch–Kincaid reading level 6.1) explaining therapy choices, risks and benefits, providing self‐rating for attribute importance for the options and self‐assessment regarding how adequate the information was in decision‐making. A total of n = 135 caregivers of food‐allergic children assessed the decision‐aid, noting good acceptability, high decisional self‐efficacy (mean score 85.9/100) and low decisional conflict (mean score 20.9/100). Information content was rated adequate and sufficient, the therapy choices wording balanced, and presented without bias for a “best choice.” Lower decisional conflict was associated with caregiver‐reported anaphylaxis. Conclusions This first pediatric OIT decision‐aid, agnostic to product, allergen, and age has good acceptability, limited bias, and is associated with low decisional conflict and high decisional self‐efficacy. It supports SDM in navigating the decision to start OIT or continue allergen avoidance.

Purpose of review This review comes at a time where new techniques in immunotherapy administration are being developed, new innovations are being incorporated to standard techniques, and new regulations are being adopted regarding the creation and storage of allergen extracts. Prior to the release of updated practice parameters regarding allergic rhinitis and immunotherapies, this review article provides a synopsis of current recommendations, a comparison of the practices in the United States and those of Europe, and an examination of experimental methods that are being studied. Recent findings This article seeks to review and discuss the various methods of administration, build up schedules, efficacy, effect on other atopic symptoms, and safety associated with allergen immunotherapy. Summary Innovations in standard techniques, such as new allergoids for SCIT, appear to be effective in improving symptoms and increasing IgG levels for grass allergens. Data for newer techniques is less clear. There appears to be increased treatment-related adverse events for ILIT, worse symptom scores compared with placebo for IDIT, and insufficient studies regarding the effectiveness of EPIT for aeroallergens. New regulations seek to standardize the documentation, storage, and creation of allergen extracts.

Food allergies (FA) pose risks beyond just the physical harm caused by anaphylaxis. The psychological consequences associated with an FA diagnosis can arguably be more detrimental for long-term health and quality of life than the consequences of an actual reaction. This can be seen in the hypervigilance of patients and caregivers surrounding mealtime, limited social interactions with peers, strained familial relationships, and increased reluctance to travel.¹ More than 40% of children with FA have experienced at least one severe food-induced reaction. Given the need for daily nourishment, the potential for a very small amount leading to a life-threatening reaction is real, so it is not surprising that fear and anxiety can overwhelm patients with this condition.¹,² Allergists have a responsibility to recognize the difference between adaptive versus maladaptive anxiety. Whereas the demands of a busy office can often dissuade prolonged in-depth conversations about mental health, there are several validated tools that can be used to quickly and efficiently identify patients at risk. Allergists can play an important role in how an FA diagnosis is conceptualized and whether families leave the office with confidence or with excessive amounts of fear. Instilling a healthy respect for foods without crippling families with anxiety should be the goal of any clinic visit. To provide optimal support and treatment for patients with increased stress and anxiety, there needs to be a more substantial and easily accessible network of mental health professionals integrated within FA treatment centers so that patients and their families have the resources to address their mental health needs.

Introduction/Background Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by intense itch and eczematous skin lesions, impacting individuals at any age. There is a need for AD treatments that provide rapid itch relief and skin clearance that are safe for long-term use. Upadacitinib is a selective, reversible oral Janus kinase 1 (JAK1) inhibitor approved in multiple countries for the treatment of moderate-to-severe AD in adults and adolescents. Objectives We evaluated the long-term safety for up to 5 years of upadacitinib 15 mg and 30 mg use in adolescents and adults with moderate-to-severe AD, based on the results of integrated data from three ongoing global pivotal Phase 3 studies. Materials & Methods The Measure Up 1, Measure Up 2, and AD Up studies are ongoing pivotal Phase 3, randomized, placebo-controlled, multicenter studies evaluating the safety and efficacy of upadacitinib 15 mg and upadacitinib 30 mg in adolescents and adults with moderate-to-severe AD. Patients were randomized 1:1:1 to receive oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily alone (Measure Up 1 and 2) or with concomitant topical corticosteroids (AD Up). At Week 16, patients receiving upadacitinib 15 mg or 30 mg during the double-blinded period continued their assigned treatment in the blinded extension (BE) period, whereas patients receiving placebo were re-randomized 1:1 to receive either upadacitinib 15 mg or 30 mg in the BE period (upadacitinib treatment for up to 260 weeks). Results A total of 2683 patients (2154 adults, 529 adolescents) who received at least 1 dose of upadacitinib (15 mg,1337; 30 mg,1346) were included in the integrated analysis. Treatment-emergent adverse events of special interest (AESI) were analyzed as exposure-adjusted rates per 100 patient-years (PY) for the entire treatment period to adjust for potentially different durations of follow-up. Rates of AESIs were similar at the 1-year analysis and up to 5-year analysis for upadacitinib for: serious infections, 15 mg, 2.3 (1 yr) and 2.2 (5 yrs)/30 mg, 2.8 (1 yr) and 2.6 (5 yrs); opportunistic infections, 15 mg, 1.6 (1 yr) and 1.7 (5 yrs)/30 mg, 1.9 (1 yr) and 2.2 (5 yrs); active tuberculosis, <0.1 at both timepoints for both doses; herpes zoster, 15 mg, 3.5 (1 yr) and 3.1 (5 yrs)/30 mg, 5.2 (1 yr) and 5.5 (5 yrs); non-melanoma skin cancer (NMSC), 15 mg, 0.3 (1 yr) and 0.4 (5 yrs)/30 mg, 0.4 (1 yr) and 0.3 (5 yrs); malignancy excluding NMSC, 15 mg, 0.1 (1 yr) and 0.3 (5 yrs)/30 mg, 0.5 (1 yr) and 0.4 (5 yrs); gastrointestinal perforations, 15 mg, 0 at both time points/30 mg, 0 (1 yr) and <0.1 (5 yrs); adjudicated major adverse cardiovascular events (MACE), 15 mg, 0.1 (1 yr) and 0.2 (5 yrs)/30 mg, <0.1 at both timepoints; adjudicated venous thromboembolic events (VTE), <0.1 for both doses at 1 year and 0.1 for both doses at 5 years. Rates of adverse events leading to death were: 15 mg, 0 (1 yr) and <0.1 (5 yrs)/30 mg, <0.1 at both timepoints. Rates of serious infection at both timepoints and doses remained low (<3.0 E/100PYs). Upadacitinib was well-tolerated by both adults and adolescents. Conclusions The integrated analysis of long-term safety data for up to 5 years indicates that rates of AESIs remained low throughout treatment with upadacitinib 15 mg or 30 mg among adults and adolescents with moderate-to-severe AD. There were no new safety risks. The current safety analysis continues to support a favorable benefit-risk profile of upadacitinib in the treatment of adults and adolescents with moderate-to-severe AD for up to 5 years of treatment, including over 7000 years of patient exposure.

Allergy/immunology specialists in the US prescribing allergy immunotherapy (AIT) have placed a heavy value on practical experience and anecdotal evidence rather than research-based evidence. With the extensive research on AIT conducted in the last few decades, the time has come to better implement evidence-based medicine (EBM) for AIT. The goal of this review was to critically assess EBM for debated concepts in US AIT practice for respiratory allergies in the context and quality of today’s regulatory standards. Debated topics reviewed were the efficacy and safety of AIT in various subgroups (e.g., polyallergic patients, older patients, patients with asthma, pregnant women), diagnosis topics (e.g., skin prick test vs allergen-specific serum IgE, factors affecting skin prick tests, use of nasal or conjunctival allergen challenges, and telemedicine for diagnosis), and dosing topics (e.g., optimal dosing for subcutaneous immunotherapy and sublingual immunotherapy tablets, US liquid allergen extract history, duration of treatment, biomarkers of efficacy). In addition, EBM for patient-centered AIT issues (e.g., adherence, use of practice guidelines, pharmacoeconomics) and the approach to implementation of AIT EBM in future clinical practice was also addressed. The EBM for each concept was briefly summarized, and when possible, a practical, concise recommendation was given.

The Food and Drug Administration (FDA) is tasked with evaluating the efficacy and safety of a drug. Despite having a regimented appraisal process in place, safety evidence can emerge during clinical trials as well as from observations and studies conducted after the drug has been on the market that might require a boxed warning. The boxed warning is the most severe warning that the FDA can give to an approved drug. It is commonly referred to as a Black Box Warning as it is outlined in the package insert by a thick black box to garner the attention of prescribers and patients. There are currently over 400 medications that have boxed warnings and the information addressing major risks associated with a particular drug may, appropriately or inappropriately, influence patient and clinician decision making. Healthcare professionals must use the best evidence and clinical judgment in determining whether to prescribe medications with these warnings. Use of an approved drug at dosages or for indications other than what it was originally licensed for is referred to as “off-label” and is legal, commonplace, and may be evidence-based. All drugs may expose patients to possible harm, so prescribers have an obligation to discuss the best available evidence regarding benefits and harms so that patients can participate in shared decision-making.

Standard criteria for ideal patient selection with food oral immunotherapy (OIT) have yet to be determined. Although there are a handful of contraindications to consider before recommending OIT, most patients with confirmed immunoglobulin E‐mediated food allergies are appropriate candidates. Success rates of OIT can vary widely and be influenced by several factors. Choosing the most appropriate candidate for an OIT program can mitigate risks and provide the best chance for patients to be successful.

Accelerated allergy shot schedules for inhalant and venom allergens provide individuals with allergy symptom relief but in a shorter time frame than conventional therapy. Accelerated immunotherapy (IT) protocols allow patients to reach therapeutic doses in a shorter time frame while improving adherence and reducing direct costs (e.g., fewer office visits and medications) and indirect costs (e.g., less travel time, missed work or school). Rush IT and cluster IT are believed to work through mechanisms similar to conventional subcutaneous IT (SCIT). The risk for severe systemic reactions during accelerated IT is low when appropriately administered; however, life-threatening and fatal reactions do occur. To reduce the incidence of systemic allergic reactions during cluster and rush IT protocols, premedication is recommended. It is important to exclude individuals at high risk such as those with poorly controlled asthma or those who are on β-blockers to mitigate the risk for developing systemic allergic reactions. However, accelerated SCIT regimens offer increased convenience, faster improvement in allergy symptoms, and the potential to reduce health-care costs while providing equivalent safety outcomes compared with conventional IT protocols.

The use of digital inhaler systems, remote patient monitoring, and remote therapeutic monitoring offer great promise as diagnostic tools and therapeutic interventions to improve adherence and inhaler technique for patients with difficult to control asthma. In turn, improvements in adherence and inhaler technique may translate into decreasing the need for high side effect treatments such as oral corticosteroids and costly therapies including biologics. While more clinical trials are needed, studies that use digital inhaler systems to collect objective real-time data on medication taking behavior via electronic medication monitors and feed this data back to patients on their mobile asthma App, and to health care professionals on the clinician dashboard to counsel patients, show positive outcomes. This manuscript addresses use of these diagnostic and therapeutic tools in asthma care, how to choose a digital inhaler system, how to teach patients to use the system, strategies for adoption of these technologies in large health care systems as well as smaller practices, coding and reimbursement, liability concerns and research gaps.