The Cost-Effectiveness of Allergen Immunotherapy Compared with Pharmacotherapy for Treatment of Allergic Rhinitis and Asthma.

This article evaluates the cost-effectiveness of allergy immunotherapy (AIT) in the treatment of allergic rhinitis, asthma, and other allergic conditions. An extensive search of the PubMed and Medline databases (up to December 2018) was conducted. There is strong evidence in the collective literature, which included individual studies and systematic reviews, that AIT is cost-effective in the management of allergic rhinitis and asthma as compared with standard drug treatment alone. The magnitude of AIT's cost-effectiveness is likely underestimated because most of the studies considered during-treatment costs and not the long-term benefits or preventive or prophylactic effects of AIT.

The Challenge of Managing Atopic Dermatitis in the United States.

BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease that affects up to 13% of children and 10% of adults in the United States. Among patients and their families, atopic dermatitis has a considerable effect on quality of life and represents a substantial economic burden. OBJECTIVE: To describe the impact and challenges of atopic dermatitis and to provide nondermatologists in the healthcare community an enhanced understanding of atopic dermatitis to facilitate treatment and pharmacy benefit discussions. DISCUSSION: Atopic dermatitis is a heterogeneous disease, and its diagnosis is hampered by a lack of objective diagnostic criteria. The current management guidelines address the distinct clinical phenotypes as a single disease and do not incorporate recent clinical advances, such as the targeting of specific inflammatory processes. The treatment guidelines for atopic dermatitis are complex and challenge healthcare providers, patients, and caregivers. Novel treatments can provide additional therapeutic options for patients with atopic dermatitis. CONCLUSIONS: Treatment options for atopic dermatitis are expanding with the development of novel anti-inflammatory therapies. An increased understanding of these advancements is necessary to optimize care for patients with atopic dermatitis.

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Safety Review of 5-Grass Pollen Tablet from Pooled Data of Clinical Trials.

BACKGROUND: The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma. OBJECTIVE: To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials. METHODS: Subjects (5-65 years old) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies. Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists could participate. Randomized subjects received a 5-grass or placebo tablet daily 2 or 4 months preseasonally and coseasonally (5 single-season studies, over 3 years in a long-term study) or outside the season (phase I studies). Adverse events were pooled and analyzed descriptively. RESULTS: Among 2,512 subjects enrolled, 1,514 received the 5-grass tablet. A total of 1,038 adults and 154 pediatric (5-17 years old) subjects were treated with the 300 Index of Reactivity dose (vs 840 and 158 placebo recipients, respectively); 17% had intermittent asthma, and 62% were polysensitized. Adverse reactions (ADRs) reported in more than 10% of actively treated subjects were mild or moderate application-site reactions, for example, oral pruritus 25% (placebo 4%) and throat irritation 21% (placebo 3%). These generally occurred during the first week of treatment and decreased over time. They led to discontinuation in less than 2.5% of subjects. None of the 3 serious ADRs were reports of anaphylaxis. No notable differences were detected in terms of incidence, nature, and severity of ADRs between adult and pediatric populations, nor between subjects with or without asthma. CONCLUSIONS: The pooled analysis in 1,514 subjects from 8 clinical studies demonstrates that the 5-grass pollen sublingual tablet has a similar good safety profile in adult and pediatric patients with or without mild, intermittent asthma.

Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles.

Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

World Allergy Organization Systemic Allergic Reaction Grading System: Is a Modification Needed?

There is no universally accepted grading system to classify the severity of systemic allergic reactions (SARs), including anaphylaxis. Although a consensus definition for anaphylaxis was established in 2005, the signs and symptoms required to define a reaction as anaphylaxis are inconsistently applied in research and clinical practice. As a result, it is difficult to compare and evaluate safety outcomes in surveys, clinical practice and trials, and pharmacovigilance data. In 2010, the World Allergy Organization (WAO) proposed a uniform grading system to classify allergen immunotherapy SARs. The basis of the grading system is the organ system(s) involved and reaction severity. The final grade is determined by the physician/health care professional after the event is over. Although the 2010 WAO grading system was developed to classify allergen immunotherapy SARs, with appropriate modifications, it can be used to classify SARs from any cause. The purpose of this Rostrum is to present a proposed modification of the 2010 WAO SAR grading system that will make it applicable to all SARs due to any cause. The modified grading system allows for classification of less severe SARs, which may be underreported or overreported in clinical trials and surveillance studies, depending on the criteria specified for adverse event reporting. The universal use of the proposed modified SAR grading system will allow for better safety comparisons across different venues and treatment protocols.

Current Evidence on Safety and Practical Considerations for Administration of Sublingual Allergen Immunotherapy (SLIT) in the United States.

Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care.

Five-grass-pollen sublingual immunotherapy tablet for the treatment of grass-pollen-induced allergic rhinoconjunctivitis: 5 years of experience.

Oralair(®) (OA) (Stallergenes, Antony, France) is a unique pre- and co-seasonal 5-grass-pollen sublingual immunotherapy tablet launched in 2008, and now approved in 31 countries worldwide for the treatment of grass-pollen allergic rhinitis and rhinoconjunctivitis. OA is the first oral treatment with a consistent, well-balanced allergen extract that mimics natural exposure and sensitization. A wealth of data exists from over 5 years of clinical and real-world experience demonstrating the efficacy and safety of OA for grass-pollen-allergy treatment. OA is highly effective from the first pollen season in all patient subgroups, including children and those with comorbid mild asthma, irrespective of sensitization status and symptom severity. OA also has sustained long-term benefits for symptom control and quality of life. This article provides an overview of the pharmacodynamics and pharmacology of OA; its efficacy, safety, tolerability and cost-effectiveness for the treatment of allergic rhinitis and rhinoconjunctivitis and its role in clinical practice.