Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori-defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

BACKGROUND: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs. OBJECTIVE: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part. RESULTS: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma. CONCLUSION: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.

Update on Omalizumab for Urticaria: What's New in the Literature from Mechanisms to Clinic.

PURPOSE OF REVIEW: Since omalizumab has been approved for urticaria, numerous randomized and real-life observational trials have been published. We reviewed the period January 2017-February 2018. RECENT FINDINGS: Omalizumab is effective for the control of urticaria recalcitrant to antihistamines in different populations globally. The ratio of total serum IgE 4-week/baseline ≥2 can predict response with a high likelihood. In observational real-life trials, doses have been adjusted on an individual basis: in some populations, up to two-thirds of the patients can be controlled with 150 mg/month; however, others are still not controlled with 300 mg/month. In these, 150 mg bimonthly could be tried, before up-dosing to 450 mg/month. On the long run (up to 3 years) omalizumab kept its efficacy. In many patients, dosing intervals could be augmented (6-8 weeks, some even more). After a 12-month treatment, about 20% showed long-term remission without relapse. Some biomarkers are being detected. Adjusting omalizumab doses in urticaria patients could enhance efficacy (shortening dosing interval and/or augmenting dose) and save costs (after 12 months: extending dosing interval and/or reducing dose).

American Academy of Allergy, Asthma & Immunology membership experience with allergen immunotherapy safety in patients with specific medical conditions.

BACKGROUND: Little data in the literature exist concerning patients with certain underlying medical conditions who receive allergen subcutaneous immunotherapy (SCIT). OBJECTIVE: To survey allergists' experience with SCIT in patients with medical conditions considered to impose an elevated risk for untoward outcomes. METHODS: A Web-based survey was conducted among members of the American Academy of Allergy, Asthma & Immunology to query about their experience with SCIT in patients with certain medical conditions. RESULTS: There were 1085 replies (21% response), of whom, 86% were U.S. based, 51% were suburban, 31% were academic, 42% were medium-sized practices, and 54% had >15 years' experience. In responders' opinion, SCIT was "contraindicated" in patients with the following: acquired immune deficiency syndrome (AIDS) (48%), cancer (and still receiving active treatment) (33%), severe asthma (32%), and a history of transplantation (30%). Even so, survey responders collectively gave SCIT to >2400 patients for each of these conditions: severe asthma, coronary artery disease, cancer in remission, and autoimmune disorders; and to ≥5400 patients with hypertension and ≥4100 women who became pregnant. The experience of colleagues with these patients rarely resulted in major problems (i.e., activation of underlying disease, systemic reactions to SCIT, or SCIT discontinuation), with the exception of severe asthma (12.5%), initiation of SCIT during pregnancy (5.4%), and AIDS (4.2%). For most other conditions, it was ≤1.5% (e.g., continue during pregnancy, cancer in remission, history of transplantation, positive human immunodeficiency virus and no AIDS). CONCLUSION: According to the experience of a large group of practicing allergists, the American Academy of Allergy, Asthma & Immunology members, few medical conditions seemed to pose an elevated risk for untoward outcomes from SCIT. Because these are survey results, prospective research might yield even more solid data.

General practitioner and patient perspectives on intranasal corticosteroids for allergic rhinitis: Treatment duration and obstacles to adherence, findings from a recent survey.

Background and objective: Currently, there are no guideline recommendations for the duration of intranasal corticosteroid (INCS) treatment for allergic rhinitis (AR). We aimed to catalogue real-world AR-INCS prescription patterns. Materials and methods: This multicenter, non-interventional, cross-sectional study used online general practitioner (GP) and patient surveys from 4 countries. Eligible GPs had 3-35 years of practical experience, regularly prescribed INCSs for AR treatment, and had managed ≥5 patients with AR per month according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in the previous year. Eligible patients with AR were non-pregnant females or males, aged 18-65 years, previous AR-INCS users (≥12 months), and receiving GP-prescribed AR therapy. Survey participants were from countries with 15-50% AR prevalence and mostly prescription-only INCS use of ≥100 million units annually (Brazil, Mexico, Spain, Thailand). GP surveys and GP-completed patient record forms (PRFs) gathered AR-care and INCS-use data over 10 months; each GP completed patient record forms (PRFs) for 3 patients with AR under their care. The patient survey reflected actual AR-INCS experience, treatment duration, and adherence factors from patient perspectives. The target sample size was 75 GPs, 75 patients, and ≥30 respondents per country. Results: From 900 GP-PRFs, the mean GP-recommended AR-INCS durations reported were 8.4 (Brazil), 8.3 (Mexico), 5.4 (Spain), and 6.4 (Thailand) weeks. From 300 patient surveys, mean reported INCS recommended durations were 6.4 (Brazil), 5.1 (Mexico), 4.0 (Spain), and 4.9 (Thailand) weeks; reported actual use durations were 6.2, 4.8, 3.6, and 6.4 weeks, respectively. The most frequent GP-PRF-reported factors influencing AR-INCS treatment duration were symptom severity (76-85%), symptom recurrence (49-73%), and existing comorbidities (33-57%). The most frequent GP-PRF-reported obstacles to adherence included forgetting to take medication regularly (54-100%), subsiding symptoms (42-91%), and being unable to continue activities (33-51%). Subsiding symptoms (36-53%) and reaching the prescription duration end (20-51%) were most frequent obstacles reported by the patient survey. Patients from all surveyed countries indicated that they visited the GP, a different physician, or a pharmacy for assistance with symptom recurrence; some patients also self-medicated. Conclusions: Real-world AR-INCS prescription durations vary between countries and actual use tends to be shorter than prescribed. Understanding underlying factors may support appropriate AR-INCS use. The study was not powered to statistically compare intercountry differences; hence, comparisons have not been drawn, and the small sample may not reflect a complete picture of clinical practice and patients with AR in each country.

Survey on immunotherapy practice patterns: dose, dose adjustments, and duration.

BACKGROUND: Practical issues dealing with the administration of allergen immunotherapy (AIT) by European and US allergists are not well known. Several concerns are only partially covered by guidelines. OBJECTIVE: To survey AIT practice patterns among worldwide members of the American Academy of Allergy, Asthma and Immunology (AAAAI). METHODS: A web-based survey was conducted among AAAAI members on dosing, dose adjustment after missed doses, and duration of AIT. RESULTS: A total of 1,201 replies (24.7% response rate of which 10% of responses were from non-US and non-Canada members). A total of 57% to 65% of the US-Canadian dosing falls within the recommended Practice Parameter ranges (9.4%-19% too low). Dose adjustment after missed doses is based on time elapsed since the last administered dose by 77% of US-Canadian and 58% of non-US-Canadian allergists. Doses are reduced when a patient comes in more than 14 days for 5 weeks after the last administration and initial dosing restarted after more than 30 days for 12 weeks since last administration during the build-up or maintenance stage. After missing 1 to 3 doses, the dosing schedules were mostly followed (build-up phase: repeat last dose, reduce by 1 dose, reduce by 2doses; maintenance phase: reduce by 1 dose, reduce by 2 doses, reduce by 3 doses). AIT is prescribed for a median of 3 years by non-US-Canadian allergists but for a median of 5 years by 75% of US-Canadian allergists. Main reasons for continuing beyond 5 years were "after stopping, symptoms reappeared" or "patient afraid to relapse." CONCLUSION: Many patients receive less than recommended doses. Two areas in which to plan further research are establishment of an optimal dose-adjustment plan for missed applications and exploration of the maximum appropriate duration of immunotherapy.

One hundred years of immunotherapy: review of the first landmark studies.

In 2011, one hundred years of allergen immunotherapy was celebrated. Several landmark studies date from the first decades of experience with this treatment and are still cited today, often without analysis of the original articles. Original articles of the oldest landmark studies on subcutaneous immunotherapy (SCIT) and sublingual immunotherapy were sought and reviewed in detail, together with some publications on their authors' historical background. Details that might be of importance to the present allergists are highlighted in this article. Study design, preparation of allergen extracts used for immunotherapy and clinical findings of the following studies are discussed. For the European school, Noon 1911 was the first report of successful application of grass pollen extract; Frankland 1954 was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT. For the European school: Noon published the first report of successful application of grass pollen extract (1911); Frankland was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT (1954). For the American line: Clowes published the first successful trial of ragweed SCIT (1913); Cooke used skin prick testing as diagnostic method (1915); Loveless used venom immunotherapy with purified venom (not whole body extract) (1956); in 1961/1968 Johnstone showed in a DBPC-RCT dose-effect of an allergen mix and highly significant asthma reduction after up to 14 yrs of treatment of asthmatic children; Lowell and Franklin did the first DB-RCT demonstrating ragweed pollen efficacy as part of a multi-allergen mix and 1967 ragweed pollen extract dose response. We discuss the first studies for SLIT in 1927 from Black (oral-IT versus SCIT) and 1986 from Scadding, DBPC-RCT with house dust mite extract. We conclude that an in-depth review of investigators' observations, methods, and thoughts, however, can also be enriching for investigators in the field today.

Evidence of effect of subcutaneous immunotherapy in children: complete and updated review from 2006 onward.

OBJECTIVE: To update the scientific evidence of subcutaneous immunotherapy (SCIT) in children. DATA SOURCES: PubMed, EMBASE, and known articles. STUDY SELECTION: All publications on SCIT in pediatric patients from January 2006 to April 2011. Study design was not a restriction. The articles were analyzed according to their outcomes and evaluated on their scientific quality using the Grading of Recommendations Assessment, Development, and Evaluation and Jadad tools. Clinical, safety, and immunologic data were gathered. RESULTS: The scientific evidence produced by the 31 articles analyzed showed that there is high-quality evidence that grass pollen SCIT causes a reduction in the combined symptom-medication score and increases the threshold of the conjunctival provocation test, immediately and 7 years after termination of SCIT, as well as the threshold of the specific bronchial provocation test and the skin prick test reactivity. Alternaria SCIT improves medication scores, combined symptom-medication scores, and quality of life. It augments the threshold in the nasal provocation test. High-quality evidence of house dust mite SCIT shows that asthma symptom and medication scores improve and emergency department visits and skin reactivity are reduced; moderate evidence indicates improvement in pulmonary function tests. Pollen SCIT prevents asthma (moderate evidence); evidence for long-term benefit of pollen SCIT (7-12 years after termination) is low to moderate. There is inconclusive evidence for SCIT reducing new sensitizations. CONCLUSION: There is acceptable evidence that shows that grass pollen, Alternaria, and house dust mite SCIT is beneficial in allergic children.

Selection of patients for sublingual versus subcutaneous immunotherapy.

Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.