12 research outputs found
International consensus on (ICON) anaphylaxis
No full textICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public.Version of Recor
Translating Chronic Urticarial Guidelines to Clinical Practice: A Study Assessing How Allergists and Dermatologists Apply Guidelines Recommendations in Argentina
No full textImpact of biologics initiation on oral corticosteroid use in the international severe asthma registry and the optimum patient care research database: a pooled analysis of real-world data
No full textAbstract: Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited. Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in SA patients from real-world specialist and primary care settings. Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, UK), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first and second year follow-up period was estimated using multivariable generalized linear models. Results: Among 5663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second year of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0-5mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61) respectively. Compared to non-initiators, biologic initiators had a substantially higher chance of achieving >75% reduction from baseline (OR [95% CI]: 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second year, respectively). These findings remained persistent and robust, when analyses were repeated with one country setting removed at a time. Conclusion: Biologic initiation in SA patients led to substantial reduction in TOCS exposure, in particular in the first year. Future analyses will explore the impact on OCS-related adverse health events
World Allergy Organization anaphylaxis guidelines: Summary
No full textThe world allergy organization guidelines for the assessment and management of anaphylaxis are being published concurrently in the journal of allergy and clinical immunology to facilitate retrieval by all health care professionals worldwide through pubmed and other search engines and in the world allergy organization journal to facilitate rapid access by all members of the wao. The recommendations for assessment and basic initial management of anaphylaxis, as summarized in fig 1, fig 2, fig 3, fig 4, fig 5 and in table 1, table 2, table 3, table 4, table 5, table 6, table 7, table 8, table 9 in the guidelines, are also being disseminated through posters, pocket cards, and applications (apps) for mobile devices.the main barriers to implementation of the recommendations in the guidelines include the erroneous perception that anaphylaxis is a rare disease and the lack of universal availability of essential medications, supplies, and equipment for its assessment and management worldwide. Additional barriers include lack of awareness that hypotension and shock are often absent in patients with anaphylaxis, that serum tryptase or plasma histamine levels are not necessarily increased, that death can occur within a few minutes, and that prompt basic initial treatment can be life-saving.the wao member societies were extensively involved in the development of these unique anaphylaxis guidelines, and will be involved with their dissemination and implementation. Their continued anaphylaxis education efforts will help to surmount the above-listed barriers.in the online full-length version of the world allergy organization guidelines for the assessment and management of anaphylaxis, available at www.jacionline.org, a complete list of references is provided to support the recommendations that are made
World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis
No full textThe illustrated World Allergy Organization (WAO) Anaphylaxis Guidelines were created in response to absence of global guidelines for anaphylaxis. Uniquely, before they were developed, lack of worldwide availability of essentials for the diagnosis and treatment of anaphylaxis was documented. They incorporate contributions from more than 100 allergy/immunology specialists on 6 continents. Recommendations are based on the best evidence available, supported by references published to the end of 2010.The Guidelines review patient risk factors for severe or fatal anaphylaxis, co-factors that amplify anaphylaxis, and anaphylaxis in vulnerable patients, including pregnant women, infants, the elderly, and those with cardiovascular disease. They focus on the supreme importance of making a prompt clinical diagnosis and on the basic initial treatment that is urgently needed and should be possible even in a low resource environment. This involves having a written emergency protocol and rehearsing it regularly; then, as soon as anaphylaxis is diagnosed, promptly and simultaneously calling for help, injecting epinephrine (adrenaline) intramuscularly, and placing the patient on the back or in a position of comfort with the lower extremities elevated. When indicated, additional critically important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions. Vital signs and cardiorespiratory status should be monitored frequently and regularly (preferably, continuously).The Guidelines briefly review management of anaphylaxis refractory to basic initial treatment. They also emphasize preparation of the patient for self-treatment of anaphylaxis recurrences in the community, confirmation of anaphylaxis triggers, and prevention of recurrences through trigger avoidance and immunomodulation. Novel strategies for dissemination and implementation are summarized. A global agenda for anaphylaxis research is proposed.</p
Real-world treatment outcomes of systemic treatments for moderate-to-severe atopic dermatitis in children aged less than 12 years:2-year results from PEDIatric STudy in Atopic Dermatitis
No full textBackground:The arrival of biologics and small-molecule therapies (eg Janus kinase inhibitors) changed atopic dermatitis treatment, but older systemic treatments continue to be prescribed. Objective: To provide real-world effectiveness, safety, and adherence data for dupilumab, cyclosporine, and methotrexate. Methods: PEDIatric STudy in Atopic Dermatitis (NCT03687359) is a real-world, prospective, observational, 10-year study of children (<12 years) with inadequately controlled moderate-to-severe atopic dermatitis. We report 2-year interim results. Results: Median treatment durations were 8.1, 13.0, and 10.7 months for dupilumab (n = 144), methotrexate (n = 114), and cyclosporine (n = 121), respectively. Dupilumab had numerically greater within-group improvements than methotrexate and cyclosporine in Eczema Area and Severity Index (−12.4∗ vs −5.7∗ and −3.3); body surface area affected (−19.9%∗ vs −11.8%∗ and −8.8%∗); itching (night-time: −2.1∗ vs −0.4 and + 0.1; daytime: −1.5∗ vs +0.1 and + 0.2; ≥6 years); itching/scratching (−3.6∗ vs −1.4∗ and −0.2; <6 years); and Patient-Oriented Eczema Measure (−7.0∗ vs −4.7∗ and −1.5) (∗P < .05 within-group improvements from baseline). Dupilumab had less discontinuations (8.3% vs 28.9% and 43.0%) and adverse event(s) (18.1% vs 29.8% and 31.4%). Limitations: No randomization, placebo, or specified dosages. Conclusion: Dupilumab was associated with numerically greater outcomes and higher adherence than cyclosporine or methotrexate.</p
Real-world treatment outcomes of systemic treatments for moderate-to-severe atopic dermatitis in children aged less than 12 years: 2-year results from PEDIatric STudy in Atopic Dermatitis
No full textBackground: The arrival of biologics and small-molecule therapies (eg Janus kinase inhibitors) changed atopic dermatitis treatment, but older systemic treatments continue to be prescribed. Objective: To provide real-world effectiveness, safety, and adherence data for dupilumab, cyclosporine, and methotrexate. Methods: PEDIatric STudy in Atopic Dermatitis (NCT03687359) is a real-world, prospective, observational, 10-year study of children (<12 years) with inadequately controlled moderate-to-severe atopic dermatitis. We report 2-year interim results. Results: Median treatment durations were 8.1, 13.0, and 10.7 months for dupilumab (n = 144), methotrexate (n = 114), and cyclosporine (n = 121), respectively. Dupilumab had numerically greater within-group improvements than methotrexate and cyclosporine in Eczema Area and Severity Index (−12.4∗ vs −5.7∗ and −3.3); body surface area affected (−19.9%∗ vs −11.8%∗ and −8.8%∗); itching (night-time: −2.1∗ vs −0.4 and + 0.1; daytime: −1.5∗ vs +0.1 and + 0.2; ≥6 years); itching/scratching (−3.6∗ vs −1.4∗ and −0.2; <6 years); and Patient-Oriented Eczema Measure (−7.0∗ vs −4.7∗ and −1.5) (∗P <.05 within-group improvements from baseline). Dupilumab had less discontinuations (8.3% vs 28.9% and 43.0%) and adverse event(s) (18.1% vs 29.8% and 31.4%). Limitations: No randomization, placebo, or specified dosages. Conclusion: Dupilumab was associated with numerically greater outcomes and higher adherence than cyclosporine or methotrexate
Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials
No full text147159Background: Many patients with chronic spontaneous urticaria (CSU) do not achieve complete control of their symptoms with current available treatments. In a dose-finding phase 2b study, ligelizumab improved urticaria symptoms in patients with H1-antihistamine (H1-AH) refractory CSU. Here, we report the efficacy and safety outcomes from two ligelizumab phase 3 studies. Methods: PEARL-1 and PEARL-2 were identically designed randomised, double-blind, active-controlled and placebo-controlled parallel-group studies. Patients aged 12 years or older with moderate-to-severe H1-AH refractory CSU were recruited from 347 sites in 46 countries and randomly allocated in a 3:3:3:1 ratio via Interactive Response Technology to 72 mg ligelizumab, 120 mg ligelizumab, 300 mg omalizumab, or placebo, dosed every 4 weeks, for 52 weeks. Patients allocated to placebo received 120 mg ligelizumab from week 24. The primary endpoint was change-from-baseline (CFB) in weekly Urticaria Activity Score (UAS7) at week 12, and was analysed in all eligible adult patients according to the treatment assigned at random allocation. Safety was assessed throughout the study in all patients who received at least one dose of the study drug. The studies were registered with ClinicalTrials.gov, NCT03580369 (PEARL-1) and NCT03580356 (PEARL-2). Both trials are now complete. Findings: Between Oct 17, 2018, and Oct 26, 2021, 2057 adult patients were randomly allocated across both studies (72 mg ligelizumab n=614; 120 mg ligelizumab n=616; 300 mg omalizumab n=618, and placebo n=209). A total of 1480 (72%) of 2057 were female, and 577 (28%) of 2057 were male. Mean UAS7 at baseline across study groups ranged from 29·37 to 31·10. At week 12, estimated treatment differences in mean CFB-UAS7 were as follows: for 72 mg ligelizumab versus placebo, –8·0 (95% CI –10·6 to –5·4; PEARL-1), –10·0 (–12·6 to –7·4; PEARL-2); 72 mg ligelizumab versus omalizumab 0·7 (–1·2 to 2·5; PEARL-1), 0·4 (–1·4 to 2·2; PEARL-2); 120 mg ligelizumab versus placebo –8·0 (–10·5 to –5·4; PEARL-1), –11·1 (–13·7 to –8·5; PEARL-2); 120 mg ligelizumab versus omalizumab 0·7 (–1·1 to 2·5; PEARL-1), –0·7 (–2·5 to 1·1; PEARL-2). Both doses of ligelizumab were superior to placebo (p<0·0001), but not to omalizumab, in both studies. No new safety signals were identified for ligelizumab or omalizumab. Interpretation: In the phase 3 PEARL studies, ligelizumab demonstrated superior efficacy versus placebo but not versus omalizumab. The safety profile of ligelizumab was consistent with previous studies. Funding: Novartis Pharma.4031042
Impact of Biologics Initiation on Oral Corticosteroid Use in the International Severe Asthma Registry and the Optimum Patient Care Research Database:A Pooled Analysis of Real-World Data
No full textBackground: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited. Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings. Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first- and second-year follow-up period was estimated using multivariable generalized linear models. Results: Among 5,663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second years of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0- to 5-mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61), respectively. Compared with non-initiators, biologic initiators had a substantially higher chance of achieving greater than 75% reduction from baseline (OR [95% CI] = 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second years, respectively). These findings remained persistent and robust when analyses were repeated with one country setting removed at a time. Conclusions: Biologic initiation in patients with SA led to substantial reduction in TOCS exposure, particularly in the first year. Future analyses will explore the impact on OCS-related adverse health events.</p
Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics
No full textRationale: Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. Objective: To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. Methods: This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. Measurements and Main Results: A total of 42, 908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake >90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; P = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; P = 0.006), major cardiovascular events (0.65 [0.44-0.97]; P = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; P = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. Conclusions: Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.</p
