Search

Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI aggregate improvement score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤ -10., Objective: Longitudinal assessment of SA patients treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement., Methods: 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy., Results: At 3 years, daily prednisolone use continued to decrease (6.9 mg/day (4.0,9.4) year-1 v 0.8 mg/day (0.0,3.7) year-3, p<0.001), OCS-related toxicity continued to decline (AIS at 3yrs -36 (-94, 19), and 61% (54/89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at year-1 and year-3 (rho 0.65, p<0.001). Nearly half (49%) met the AIS MCID at both year-1 and 3, but 29% of the cohort did not meet the AIS MCID at either timepoint. Toxicity change at year-1 was predictive of toxicity change at year-3 for 79%. Toxicity reduction was not proportional to OCS reduction, there were no pre-biologics characteristics that predicted toxicity reduction., Conclusion: After 3 years of biologic treatment, 61% of SA patients had clinically significant toxicity improvement. Individual toxicity outcomes at year-1 are associated with longitudinal outcomes suggesting that for some, additional interventions are needed alongside OCS-reduction to decrease morbidity., (Copyright © 2024. Published by Elsevier Inc.)

Background: Today, single-inhaler ICS/LAMA/LABA (SITT) COPD therapies are available. It is unclear whether they are more effective than multiple-device triple therapies (MITT) in improving COPD outcomes. Methods : We retrospectively considered patients on SITT/MITT in 2019/2020 who were prescribed >7 packages of ICS/LABA/LAMA or ICS/LAMA (+LAMA). The two treatments were compared concerning systemic corticosteroids, antibiotics, salbutamol, antifungal prescriptions, and number of emergency room visits/hospitalizations (ERV/Hs). We studied 292 MITT patients (Group A) during 2019, switching to SITT in 2020, and 366 subjects (Group B) who took SITT during 2019, and 206 MITT individuals (Group C) in 2020. Results: ICS/LABA + LAMA (MITT) package use was 8.2 ± 4.2 and 7.85 ± 4 in 2019, switching to 11.2 ± 3.2 when patients shifted to SITT in 2020 ( p = 0.0001). Group A MITT package use was lower than in SITT patients in 2019 (9.31 ± 2.71, p = 0.0001; Group B). Throughout 2020, Group C (10.3 ± 6.1 packs) adherence to ICS/LABA was similar to SITT adherence in Group A ( p = 0.270), whereas LAMA package use (9.1 ± 5) was lower ( p = 0.0038). Patients using systemic corticosteroids/antibiotics were fewer in SITT in 2020, compared to the MITT results in 2019. Subjects with fewer ERV/Hs were observed with SITT rather than with MITT. Particularly, 13.8% of patients needed ≥2 ERV/Hs when treated with SITT, whereas 19.2% needed ≥2 ERV/Hs with MITT in 2019 ( p = 0.08). Multivariate analysis, adjusted for all confounding factors including treatment adherence, showed that MITT (vs. SITT) can have an increased risk of at least one ERV/H (subjects receiving MITT during 2019 passing to SITT in 2020, OR: 1.718 [1.010-2.924], p = 0.046; Group A/MITT/2019 vs. Group B/SITT/2019, OR: 1.650 [0.973-3.153], p = 0.056; Group C/MITT/2020 vs. Group B/SITT/2019, OR: 1.908 [1.018-3.577], p = 0.044). Conclusions: SITT therapy may promote treatment adherence more effectively, therefore, reducing COPD exacerbations better than MITT. A possible synergistic effect of ICS/LABA/LAMA intake with a single device might be another cause of SITT's greater efficacy.

Objective: Patients' perceptions of asthma symptoms, and attitudes regarding diagnosis and management, can affect their ability to reach good asthma control. The aim of the study was to explore patients' perceptions of asthma management, with focus on treatment with oral corticosteroids (OCS)., Methods: A DOXAPHARMA survey was conducted. A questionnaire with 46 multiple choice questions was completed by 50 patients with severe uncontrolled asthma, and 258 with mild-moderate controlled or partly controlled asthma. Participants were representative of Italian asthmatic patients-with medium age, long asthma duration, delayed diagnosis, poor asthma control, and frequent exacerbations., Results: Many asthmatics reported inadequate pharmacologic treatment. The majority but not all patients regularly used ICS/LABA. Oral treatment was common, mainly with OCS, particularly in severe asthmatics. One-fourth of patients did not regularly use inhaled therapy, and adherence was poor, resulting in frequent OCS use to treat exacerbations, which were common in mild-moderate cases. Patients were fairly satisfied with asthma therapies, but many had concerns about long-term corticosteroid use. Patients complained about poor management of comorbidities associated with asthma and OCS use, but were generally satisfied with their patient/doctor relationships. Many patients failed to achieve optimal health-related quality of life (HRQoL), mainly those with severe asthma who used OCS treatment and emphasized how OCS therapy impacted QoL., Conclusions: The survey results confirmed many problems related to mild-moderate and severe asthma management in Italy and highlighted the overuse of OCS rather than more effective and safe treatments, which had strong negative effects on HRQoL.

Background: Type 2 low-severe asthma phenotype is often a result of corticosteroid-overtreated type 2 disease owing to persistent symptoms, often unrelated to asthma and unlikely to respond to high-dose corticosteroid treatment., Objective: This study aimed to characterize patients with severe asthma with low eosinophil counts (<300 cells/μL) and describe their disease burden and treatment across health care settings in the United Kingdom., Methods: A retrospective cohort study of patients with severe asthma using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients according to the latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and health care resource use were described by baseline BEC (≤150 and >150 to <300 cells/μL)., Results: Analysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; 60.5% and 59.4% had BECs 150 cells/μL or less at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (two or more exacerbations) at follow-up (12 months after the index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance oral corticosteroid use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 μg short-acting β 2 agonist or >500 μg terbutaline/d in CPRD-HES: 48.8%; median Asthma Control Questionnaire-6 score in UKSAR: 2.0 [range, 1.0-3.3]). Health care resource use was similar across BEC groups., Conclusions: Most patients managed in primary care experienced infrequent exacerbations, whereas UKSAR patients had frequent exacerbations. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance oral corticosteroids, increasing the risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4-10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission - a step closer to the concept of cure - a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2024/09/dic.2024-7-2-COI.pdf, (Copyright © 2024 Bosi A, Lombardi C, Caruso C, Cottini M, Baglivo I, Colantuono S, Menzella F.)

Introduction: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma., Methods: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants., Results: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice., Conclusions: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy., (© 2024. The Author(s).)

Objective: Initiated by the Severe Asthma Network Italy (SANI), this study aims to explore asthma patients' perceptions of disease severity, differentiating between mild and severe asthma. The objective is to identify factors influencing tailored treatment strategies for varying disease severities and to provide insights into asthma care in Italy., Methods: Conducted between November 2020 and January 2021, a survey using Computer-Assisted Personal Interviewing (CAPI) collected data from 308 Italian adults, representing the population. A 25 item multiple choice questionnaire covered asthma diagnosis, symptoms, treatment approaches, associated conditions, and quality of life., Results: Among participants, 83.8% reported having mild asthma, while 16.2% had severe asthma. Severe asthma patients had longer disease durations, more severe symptoms, frequent exacerbations, and higher hospital/ER visits. Although treatment adherence and symptom profiles generally aligned with international guidelines for self reported severe asthma, 22% of self identified mild asthmatics experienced severe respiratory symptoms. Oral corticosteroid (OCS) use was observed in 50% of severe cases and 22% of mild cases. Adherence was higher in severe asthma patients (76%) versus mild asthma patients (28%). Both groups experienced comorbidities, with 96% of severe asthmatics and 72% of mild asthmatics reporting impaired quality of life., Conclusion: This study highlights the disparity between clinical categorization and patient perceptions of asthma severity. The prevalence of self reported severe asthma exceeds literature data. The burden of mild asthma remains significant, with treatment approaches not fully aligned, particularly regarding disproportionate OCS use. Addressing this gap requires enhancing patient education, improving diagnostic practices, and promoting adherence., Competing Interests: FB received financial grants from AstraZeneca, Chiesi Farmaceutici S.p.A and Insmed Inc.; he worked as a paid consultant for Menarini and Zambon; and received speaker fees from AstraZeneca, Chiesi Farmaceutici S.p.A., GlaxoSmithKline, Guidotti, Grifols, Insmed Inc., Menarini, Novartis AG, SanofiGenzyme, Viatris Inc., Vertex Pharmaceuticals and Zambo; CM received grants from AZ, GSK, Sanofi; GWC reports having received research grants as well as being lecturer or having received advisory board fees from: A. Menarini, Allergy Therapeutics, AstraZeneca, Chiesi Farmaceutici, Faes, Firma, GuidottiMalesci, Glaxo Smith Kline, Hal Allergy, Innovacaremd, Novartis, OmPharma, RedMaple, SanofiAventis, SanofiGenzyme, StallergenesGreer, Uriach Pharma, ThermoFisher, Valeas; EH received a research grant from GlaxoSmith&Kline, and fees for lectures from Sanofi, Regeneron, GlaxoSmith&Kline, AstraZeneca, Novartis, Chiesi, StallergenesGreer; and declares fees for advisory boards participation from Sanofi, Regeneron, Glaxo Smith Kline, AstraZeneca, Novartis, Chiesi, Almirall, Celltrion Healthcare, Bosch; PP received advisory board fees from Chiesi Farmaceutici, Glaxo Smith Kline, and Sanofi, and fees for educational activities from: AstraZeneca, Chiesi Farmaceutici, Glaxo Smith Kline, Guidotti and Sanofi; GS received grants from AZ, GSK, Sanofi, Novartis. The authors declare that they have no relevant conflicts of interest for the present manuscript., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) has a negative impact on their quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating antibiotics, systemic corticosteroids, and multiple surgeries. The aim of this study was to assess the efficacy of dupilumab in reducing frontal pain and the need for rescue treatments for recalcitrant frontal sinusitis in patients with CRSwNP. We enrolled a cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated with severe facial pain measured by MIDAS score who were treated with dupilumab 300 mg every 2 weeks and followed for at least 12 months. The mean MIDAS score decreased from 45.6 ± 10.7 at baseline to 1.3 ± 2.3 at 6 months ( p < 0.05). VAS craniofacial pain decreased from 7.3 ± 1.6 at baseline to 1.2 ± 1.5 at 6 months ( p < 0.05). No patient needed oral corticosteroids during treatment with dupilumab ( p < 0.05), and the use of analgesics decreased from 9.6 ± 3.1 NSAID pills/week in the last 2 months at baseline to 0.6 ± 1.3 at 1 year of follow-up ( p < 0.05). Our results demonstrated that use of subcutaneous dupilumab can improve symptom control, including recurrent severe cranio-facial pain, and reduce the need for rescue medical treatments (systemic steroids and NSAID) in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis.

Background: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial., Objectives: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP., Methods: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS)., Planned Outcomes: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36., Conclusion: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis., Clinical Trial Registration: ClinicalTrials.gov identifier NCT04206553., (© 2024. Crown.)

In the Middle East and Africa (MEA) region, overuse of oral corticosteroids (OCS) for asthma management, both as burst and maintenance therapy, poses a significant challenge. Gaps in knowledge regarding the need to taper OCS in patients with severe asthma and the use of OCS in comorbid conditions have been noted. OCS stewardship can help attain optimal and effective OCS tapering along with reducing OCS overuse and over-reliance. In this paper, we discuss current practices regarding the use of OCS in asthma, globally and in the MEA region. Expert recommendations for achieving OCS stewardship in the MEA region have also been presented. Regional experts recommend increasing awareness among patients about the consequences of OCS overuse, engaging community pharmacists, and educating primary healthcare professionals about the benefits of prompt appropriate referral. Innovative local referral tools like ReferID can be utilized to refer patients with asthma to specialist care. The experts also endorse a multidisciplinary team approach and accelerating access to newer medicines like biologics to implement OCS stewardship and optimize asthma care in the MEA region., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MAA received advisory board and lecture honoraria from AstraZeneca, Sanofi, and GSK. AAZ received honoraria from GSK, AstraZeneca, Sanofi, and Novartis. HAA received speaker honoraria from AstraZeneca, Merck & Co., Inc., Servier Laboratories, and Menarini; received support for attending meetings and traveling from Cipla Ltd., and Servier Laboratories. MI received honoraria for lectures and support for attending meetings from AstraZeneca., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription., Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥90-day gap] and frequent [<90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns., Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£3902 vs £2722 and £8623 vs £4929, respectively), as were mean annualized costs (£565 vs £313 and £1526 vs £634, respectively). A dose-response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001)., Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care., Competing Interests: CA, HH, JSKC, VC and WH are employees of Observational and Pragmatic Research Institute, Singapore, who conducted this study, funded by AstraZeneca. WH reports grants from AstraZeneca, during the conduct of the study; grants from Chiesi Pharmaceuticals, outside the submitted work. VC works for The Optimum Patient Care Global who received funding/grant for the study. DP has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Mylan, Novartis, Regeneron, Sanofi. Thermofisher Scientific and Viatris; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Medscape, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Teva Pharmaceuticals, Theravance Biopharma, Viatris and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi, Theravance, UK National Health Service and Viatris; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Inside Practice, Kyorin, Medscape, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi, Teva Pharmaceuticals and Viatris; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Teva Pharmaceuticals and Thermofisher; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. JC, EM, AMG, and TNT are employees of, and own stock in, AstraZeneca. JH reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Circassia and Teva unrelated to the conduct of the study. AB has received consultancy fees and speakers’ fees from of AstraZeneca, Amgen, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi and Regeneron, and research grants from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline. AMG is an employee of, and owns stock in, AstraZeneca and has received grants, advisory board fees, lecture fees and consulting fees from AstraZeneca; advisory board fees from GlaxoSmithKline; advisory board fees and lecture fees from Novartis; advisory board fees, lecture fees and travel expenses from Teva; advisory board fees from Regeneron; and advisory board fees, lecture fees and consulting fees from Sanofi. DJJ has received consultancy fees and speakers’ fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Sanofi and Regeneron, and research grants from AstraZeneca., (© 2024 Tran et al.)

Systemic administration of corticosteroids is used in the treatment of chronic eosinophilic pneumonia (CEP). However, in patients with CEP as well as other comorbidities, the adverse effects of corticosteroids should be minimized as much as possible. A 71-year-old woman was presented with aggravating asthma with CEP and sinusitis, and she had uncompensated liver cirrhosis (LC) with a Child-Pugh score of 7. Initial treatment with a low dose of oral corticosteroids (OCSs) in combination with tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody, resulted in rapid improvement of asthma and CEP without deteriorating LC. Sinusitis also improved after ceasing OCS. This case suggested that tezepelumab may be useful as a treatment option for patients with CEP, especially those with liver dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Inaba, Shimizu, Nakamura, Okutomi, Takemasa and Niho.)

In this case report, we highlight a rare case of palindromic rheumatism (PR) presenting as polymyalgia rheumatica (PMR). Many challenges and complexities are associated with diagnosing and treating PR. Literature reviews showed only a few case reports of this unique presentation. PR has a distinct presentation that often goes unnoticed and is misinterpreted by medical professionals. A more thorough clinical approach is required to identify and treat this condition. We hope sharing such uncommon cases will help the medical community better understand PR and develop improved diagnostic and therapeutic options. This case also demonstrates the need for further research to better understand the pathogenesis of this uncommon condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Farooq et al.)

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown., Objective: To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA., Methods: We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed., Results: A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups., Conclusions: In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Urinary eicosanoid concentrations reflect inflammatory processes in multiple diseases and have been used as biomarkers of disease as well as suggested for patient stratification in precision medicine. However, implementation of urinary eicosanoid profiling in large-scale analyses is restricted due to sample preparation limits. Here we demonstrate a single solid-phase extraction of 300 µL urine in 96-well-format for prostaglandins, thromboxanes, isoprostanes, cysteinyl-leukotriene E 4 and the linoleic acid-derived dihydroxy-octadecenoic acids (9,10- and 12,13-DiHOME). A simultaneous screening protocol was also developed for cortisol/cortisone and 7 exogenous steroids as well as 3 cyclooxygenase inhibitors. Satisfactory performance for quantification of eicosanoids with an appropriate internal standard was demonstrated for intra-plate analyses (CV = 8.5-15.1%) as well as for inter-plate (n = 35) from multiple studies (CV = 22.1-34.9%). Storage stability was evaluated at - 20 °C, and polar tetranors evidenced a 50% decrease after 5 months, while the remaining eicosanoids evidenced no significant degradation. All eicosanoids were stable over 3.5-years in urine stored at - 80 °C. This method will facilitate the implementation of urinary eicosanoid quantification in large-scale screening., Competing Interests: Declaration of Competing Interest JK receives consulting fees from Gesynta Pharma AB., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Trial data demonstrate that mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, is effective for patients with severe asthma and comorbid chronic rhinosinusitis (CRS) with nasal polyps. This real-world, retrospective cohort study investigated mepolizumab for US patients with severe asthma and CRS with/without sinus surgery., Methods: IQVIA PharMetrics Plus claims data from baseline and follow-up (12 months before and after mepolizumab initiation) were used to analyze three patient cohorts: cohort 1 (severe asthma only); cohort 2 (severe asthma + comorbid CRS without sinus surgery); and cohort 3 (severe asthma+comorbid CRS+sinus surgery), allowing for cross-cohort comparisons., Results: The analysis included 495, 370, and 85 patients in cohort 1, cohort 2, and cohort 3, respectively. Systemic and oral corticosteroid use was lower for all cohorts after mepolizumab initiation. In cohort 3, asthma rescue inhaler and antibiotic use were lower during follow-up than baseline. Asthma exacerbations were reduced by 28% to 44% comparing follow-up versus baseline, with the largest reduction in cohort 3 (ratio of incidence rate ratio [RR] vs cohort 1: 0.76; p = 0.036). Reductions in oral corticosteroid claims were greater following mepolizumab initiation for cohort 3 versus cohort 1 (RR, 0.72; p = 0.011) and cohort 2 (RR, 0.70; p < 0.01). In cohorts 1 through 3, outpatient and emergency department visits were reduced by 1 to 2 and 0.4 to 0.6 visits annually, asthma-related and asthma exacerbation-related total costs were reduced by $387 to $2580 USD, and medical costs were reduced by $383 to $2438 USD during follow-up., Conclusions: Consistent with trial data, mepolizumab use in real-world practice shows benefits across comorbid patient cohorts with more a pronounced impact in those with severe asthma+comorbid CRS + sinus surgery., (© 2023 ARS-AAOA, LLC.)

Introduction: Asthma is a chronic inflammatory disease that can lead to airways remodeling. Despite their well-known side-effects, oral corticosteroids (OCS) continue to be used to reduce exacerbations and control asthma symptoms in many patients., Case Study: We describe two cases of uncontrolled severe asthma characterized by systemic clinical consequences of prolonged OCS use, such as diabetes, weight gain, and osteoporosis., Results: Both patients were treated with Dupilumab. During follow-up both patients showed an improvement in asthma control and were able to gradually taper the OCS dose, thus reducing the clinical burden associated with hypercortisolism., Conclusion: Dupilumab was able to control both the inflammatory-induced "airway remodeling" as well as the OCS-induced "patient remodeling".

Purpose: Real-world asthma control data among patients initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) are limited. This study assessed rescue medication use and asthma-related exacerbations in patients with asthma before and after initiating single-inhaler FF/UMEC/VI using administrative claims data., Patients and Methods: This retrospective, pre-post cohort study analyzed data from the IQVIA PharMetrics Plus database (September 18, 2016‒March 31, 2020). Patients aged ≥18 years that had ≥1 dispensing of single-inhaler FF/UMEC/VI 100/62.5/25 mcg (first dispensing = index date), ≥12 months of continuous health insurance enrollment prior to (pre-treatment) and following (post-treatment) FF/UMEC/VI initiation and ≥1 diagnosis of asthma during the pre-treatment period or on the index date were included. The primary endpoint was the number of oral corticosteroid (OCS) dispensings per patient per year during pre- and post-treatment periods. Secondary endpoints included asthma-related exacerbation rates and short-acting β 2 -agonist (SABA) use. Comparisons between pre- and post-treatment periods were made using risk and rate ratios., Results: Overall, 890 patients with asthma initiating treatment with FF/UMEC/VI were included. The most recently dispensed controller medications prior to FF/UMEC/VI initiation were inhaled corticosteroids/long-acting β 2 -agonists (33.5%) and leukotriene modifiers (33.0%). Patients had a 29% reduction in the number of OCS dispensings (rate ratio [95% confidence interval (CI)]: 0.71 [0.65, 0.77], P < 0.001) during post-treatment versus pre-treatment, with a 23% reduction in the proportion of patients with ≥1 OCS dispensing post-treatment (risk ratio [95% CI]: 0.77 [0.73, 0.82], P < 0.001). Significant reductions in rates (rate ratio [95% CI]) of asthma-related exacerbations (0.59 [0.52, 0.67], P < 0.001) and SABA use (0.80 [0.74, 0.86], P < 0.001) were also observed., Conclusion: In this real-world study, patients with asthma had significantly lower OCS use, asthma-related exacerbations, and SABA use following treatment initiation with FF/UMEC/VI compared with their pre-treatment period. These results suggest better asthma control following initiation of FF/UMEC/VI in a routine clinical practice setting., Competing Interests: KD, SGN, and RP are employees of GSK and hold stock and shares at GSK. MB is a former employee of GSK and holds stocks and shares at GSK. GG, FL, MM, and MSD are employees of Analysis Group, a consulting company that received research funds from GSK to conduct this study but did not receive payment for manuscript development. MSD also reports that Analysis Group has received grants from AbbVie, Apellis, AstraZeneca, Ayala Pharmaceuticals, Bayer, Blueprint Medicines, GSK, Humacyte, Janssen, Merck, Novartis, Pfizer, Sanofi, and Takeda, outside the submitted work. RB is a staff Pulmonary Physician at the National Jewish Health and is on speaker bureaus and advisory boards for GSK, AstraZeneca, Sanofi, Merck, and Regeneron. The authors report no other conflicts of interest in this work., (© 2023 Bogart et al.)

Purpose: Oral corticosteroids (OCS) play a role in the treatment of acute chronic obstructive pulmonary disease (COPD) exacerbations; however, chronic use is not recommended due to the high rate of systemic complications, development of comorbidities, and increased mortality. Data assessing the real-world impact of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) on OCS utilization rates are limited. This study assessed the impact of FF/UMEC/VI on OCS use among patients with COPD previously treated with OCS., Patients and Methods: A retrospective database study of patients with COPD aged ≥40 years who initiated FF/UMEC/VI from 1 November 2017 to 31 December 2018, identified through the MarketScan ® Commercial and Medicare Supplemental databases. Patients were required to have ≥1 dispensing of an OCS prior to initiation of FF/UMEC/VI (index) and were followed up for 12 months post-index. OCS utilization patterns, potential OCS-related adverse events, healthcare resource utilization (HCRU), and costs were compared between the 12-month pre- and post-index periods., Results: A total of 2013 patients were identified (mean age 63.5 years, 55.7% female). The proportion of patients with ≥1 OCS claim decreased by 32.2% between the pre- and post-index period (67.8% vs 100%; p < 0.001). Comparing the post-index period to the pre-index period, mean number of OCS pharmacy claims per patient decreased from 3.3 to 2.5 (p < 0.001) and mean daily dose was reduced from 3.1 to 2.6 mg/day (p = 0.004); 30.0% of patients reduced their daily dose by 90-100%. Reductions were also seen in COPD-related HCRU. The proportion of patients with an inpatient admission for COPD decreased from 11.4% to 7.1% (p < 0.001), emergency room visits decreased from 23.1% to 17.4% (p < 0.001), and office visits from 97.5% to 90.1% (p < 0.001). Similar results were seen for all-cause HCRU., Conclusion: Among patients with COPD with prior OCS use, FF/UMEC/VI initiation resulted in significant reductions in OCS utilization, COPD-related HCRU (including hospitalization), and all-cause HCRU., Competing Interests: MBo, CBA, and MBa were employees of, and/or shareholders in, GSK at the time of study. DM and ERP are employees of Merative (IBM Watson Health at the time of study), which received research funds from GSK to conduct this study, but not for manuscript development. KD is an employee of, and/or shareholder in, GSK. The authors report no other conflicts of interest in this work., (© 2023 Bogart et al.)

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests., Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised., Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases., Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations., Competing Interests: Breda Cushen has received honoraria for lectures from AstraZeneca, Novartis and Boehringer Ingelheim. Mariko Siyue Koh reports grant support from AstraZeneca, and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GlaxoSmithKline, AstraZeneca, Novartis, Sanofi and Boehringer Ingelheim, outside the submitted work. Trung N. Tran is an employee of AstraZeneca, a co-funder of the International Severe Asthma Registry. Neil Martin is an employee of AstraZeneca, a co-funder of the International Severe Asthma Registry. Ruth Murray declares no relevant conflicts of interest in this work. Thendral Uthaman is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Celine Yun Yi Goh is an employee of Optimum Patient Care Global (OPCG), a co-funder of the International Severe Asthma Registry. Rebecca Vella is an employee of Optimum Patient Care, a co-funder of the International Severe Asthma Registry. Neva Eleangovan was an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Lakmini Bulathsinhala is an employee of the Observational and Pragmatic Research Institute (OPRI). OPRI conducted this study in collaboration with Optimum Patient Care and AstraZeneca. Jorge F Maspero reports speaker fees, grants or advisory boards for AstraZeneca, Sanofi, GSK, Novartis, Inmunotek, Menarini, Noucor. Matthew J Peters declares personal fees and non-financial support from AstraZeneca and GlaxoSmithKline. Florence Schleich reports consultancy work for GSK, AstraZeneca, Sanofi - Advisory board, received speaker fees from GSK, AstraZeneca, Chiesi, Amgen, TEVA and research grants from GSK, AstraZeneca, Chiesi. Paulo Pitrez received fees as speaker or for consultations from GSK, AstraZeneca, Novartis, Sanofi, and Boehringer Ingelheim. George Christoff declares no relevant conflicts of interest in this work. Mohsen Sadatsafavi has received honoraria from AZ, BI, TEVA, and GSK for purposes unrelated to the content of this manuscript and has received research funding from AZ and BI directly into his research account from AZ for unrelated projects. Carlos A. Torres-Duque has received fees as advisory board participant and/or speaker from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis and Sanofi-Aventis; has taken part in clinical trials from AstraZeneca, Novartis and Sanofi-Aventis; has received unrestricted grants for investigator-initiated studies at Fundacion Neumologica Colombiana from AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Grifols and Novartis. Celeste Porsbjerg has attended advisory boards for AstraZeneca, Novartis, TEVA, and Sanofi-Genzyme; has given lectures at meetings supported by AstraZeneca, Novartis, TEVA, Sanofi-Genzyme, and GlaxoSmithKline; has taken part in clinical trials sponsored by AstraZeneca, Novartis, MSD, Sanofi-Genzyme, GlaxoSmithKline, and Novartis; and has received educational and research grants from AstraZeneca, Novartis, TEVA, GlaxoSmithKline, ALK, and Sanofi-Genzyme. Alan Altraja has received lecture fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, GlaxoSmithKline, MSD, Norameda, Novartis, Orion, Sanofi, and Zentiva; sponsorships from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, GlaxoSmithKline, MSD, Norameda, Novartis, and Sanofi; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi, and Teva. Lauri Lehtimäki has received personal fees from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Orion Pharma and Sanofi. Arnaud Bourdin has received industry-sponsored grants from AstraZeneca-MedImmune, Boehringer-Ingelheim, Cephalon/Teva, GlaxoSmithKline, Novartis, Sanofi-Regeneron and consultancies with AstraZeneca-MedImmune, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Regeneron-Sanofi, Med-in-Cell, Actelion, Merck, Roche, and Chiesi. Christian Taube declares no relevant conflicts of interest in this work. Nikolaos G. Papadopoulos has been a speaker and/or advisory board member for Abbott, Abbvie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GSK, HAL, Faes Farma, Medscape, Menarini, MSD, Mylan, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, Viatris. He also reports research support from Capricare, Nestle, Numil, Vianex, and REG, outside the submitted work. Zsuzsanna Csoma declares no relevant conflicts of interest in this work. Unnur Bjornsdottir receives gratuities for lectures/presentations from AstraZeneca, Sanofi and Novartis. Sundeep Salvi declares research support and speaker fees from Cipla, Glenmark, GSK. Enrico Heffler declares personal fees from: Sanofi, Regeneron, GSK, Novartis, Astrazeneca, Stallergenes, Circassia. Takashi Iwanaga received lecture fees from Kyorin, GlaxoSmithKline, Novartis, Boehringer Ingelheim and AstraZeneca. Mona Al-Ahmad has received advisory board and speaker fees from AstraZeneca, Sanofi, Novartis, and GlaxoSmithKline. Received a grant from Kuwait Foundation for the Advancement of Sciences (KFAS). Désirée Larenas Linnemann reports personal fees from Allakos, Amstrong, AstraZeneca, Bayer, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Sanofi, Siegfried, UCB, Carnot, grants from Sanofi, Lilly, Pfizer, Abbvie, AstraZeneca, Novartis, Circassia, UCB, GSK, Purina institute, outside the submitted work. She also reports speaker’s bureau, safety board, Advisory board for ALK, Allakos, Amstrong, Astrazeneca national and global, Bayer, Chiesi, Grunenthal, Grin, GSK national and global, Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Carnot; support with congresses from Abbvie, Lilly, Sanofi, Astrazeneca, Pfizer, Novartis, GSK, Purina institute. Job F.M. Van Boven received grants and/or consultancy fees from AstraZeneca, Chiesi, European Commission COST (COST Action 19132), GSK, Lung Alliance Netherlands, Novartis, Teva, and Trudell Medical, outside the submitted work and all paid to his institution. Bernt Bøgvald Aarli reports grants from Boehringer Ingelheim during the conduct of the study and personal fees from Boehringer Ingelheim, AstraZeneca, GSK, Sanofi-Aventis Norway, Chiesi, Boehringer Ingelheim, and Novartis Norway, outside the submitted work. Piotr Kuna reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, Celon Pharma, Chiesi, FAES, Glenmark, GSK, Novartis, Polpharma, Boehringer Ingelheim, Sandoz, Teva, Zentiva, outside the submitted work. Cláudia Chaves Loureiro declares research Grant (P.I., collaborator or consultant: AstraZeneca, GSK; Speakers Bureau / Honoraria: AstraZeneca, GSK, Novartis, Teva, Sanofi; Consultant / advisory board: AstraZeneca, Bial, GSK, Jaba Recordatti, Novartis, Teva, Sanofi. Riyad Al-Lehebi has given lectures at meetings supported by AstraZeneca, Boehringer Ingelheim, Novartis, GlaxoSmithKline, and Sanofi, and participated in advisory board fees from GlaxoSmithKline, AstraZeneca, Novartis, Abbott. Jae Ha Lee declares no conflicts of interest in this work. Nuria Marina Malanda reports grants, personal fees and non-financial support from AstraZeneca, GSK, Teva, Novartis, Sanofi, and Pfizer, outside the submitted work. Leif Bjermer has (in the last three years) received lecture or advisory board fees from Alk-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mundipharma, Novartis, Sanofi, Genzyme/Regeneron, and Teva. Chau-Chyun Sheu has received speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Pfizer, and has acted as an investigator for trials sponsored by AstraZeneca, Novartis, Roche, Sanofi-Regeneron, Galapagos, Shionogi, Aridis, Bristol Myers Squibb, Insmed and Horizon Therapeutics. Bassam Mahboub reports no conflicts of interest in this work. John Busby has received personnel from NurvAir. Andrew N. Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva, and has received speaker fees from AstraZeneca, Novartis, Teva and Sanofi. He has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva. He has had consultancy agreements with AstraZeneca and Sanofi. Eileen Wang has received honoraria from AstraZeneca, GlaxoSmithKline, Wefight, and Clinical Care Options. She has been an investigator on studies sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Sanofi and Sema4, Novartis, and Teva, for which her institution has received funding. David B Price has advisory board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; consultancy agreements with AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Viatris, Teva Pharmaceuticals; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Chiesi, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Commute Digital, Medscape, Viatris, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Novartis, Medscape, Viatris, Teva Pharmaceuticals; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline., (© 2023 Cushen et al.)

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC)., Aims: To evaluate real-world data in US patients with UC receiving tofacitinib., Methods: Characteristics and outcomes of patients with UC initiating tofacitinib between 2018 and 2019 were assessed using data from the IBM® MarketScan® claims database. The index date was the first tofacitinib claim; pre- and post-index periods were 12 months. Outcomes included tofacitinib adherence/persistence, oral corticosteroid (OCS) use, and healthcare resource utilization (HCRU) and costs., Results: Of 276 patients with UC who initiated tofacitinib, 68 (24.6%) were bio-naïve, and 208 (75.4%) bio-experienced. At month 12, overall median tofacitinib adherence (proportion of days covered) was 0.82 (mean 0.68); 43.8% of patients discontinued tofacitinib (90-day gap). Of patients receiving OCS during the post-index 16-week tapering period, 40.4% discontinued OCS up to 12 months post-index. OCS use decreased in patients continuing tofacitinib versus those discontinuing tofacitinib (29.7% vs 59.5%, respectively). Reductions in all-cause and UC-related outpatient visits were observed for bio-naïve (- 1.34 and - 0.88, respectively) and bio-experienced (- 4.72 and - 5.16, respectively) patients, post-index. Decreased UC-related costs per year were observed for bio-experienced patients (difference in post-index vs pre-index, - US$12,448; driven by changes in pharmacy costs), but not for bio-naïve patients (US$47,152)., Conclusions: In this real-world analysis in a mostly bio-experienced population, the majority of US patients with UC initiating tofacitinib remained on therapy at 12 months, and OCS use was reduced with tofacitinib treatment. HCRU (all patients) and UC-related costs were reduced in bio-experienced patients. The majority of patients with ulcerative colitis starting tofacitinib in this real-world study continued therapy at 12 months; there was a reduction in the use of steroids, and a decrease in healthcare resournce utilization and costs., (© 2023. The Author(s).)

Background: Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids., Objectives: We sought to analyze whole blood transcriptome from 738 samples in T2-biomarker-high/-low patients with severe asthma to relate transcriptomic signatures to T2 biomarkers and asthma symptom scores., Methods: Bulk RNA-seq data were generated for blood samples (baseline, week 24, week 48) from 301 participants recruited to a randomized clinical trial of corticosteroid optimization in severe asthma. Unsupervised clustering, differential gene expression analysis, and pathway analysis were performed. Patients were grouped by T2-biomarker status and symptoms. Associations between clinical characteristics and differentially expressed genes (DEGs) associated with biomarker and symptom levels were investigated., Results: Unsupervised clustering identified 2 clusters; cluster 2 patients were blood eosinophil-low/symptom-high and more likely to be receiving oral corticosteroids (OCSs). Differential gene expression analysis of these clusters, with and without stratification for OCSs, identified 2960 and 4162 DEGs, respectively. Six hundred twenty-seven of 2960 genes remained after adjusting for OCSs by subtracting OCS signature genes. Pathway analysis identified dolichyl-diphosphooligosaccharide biosynthesis and assembly of RNA polymerase I complex as significantly enriched pathways. No stable DEGs were associated with high symptoms in T2-biomarker-low patients, but numerous associated with elevated T2 biomarkers, including 15 that were upregulated at all time points irrespective of symptom level., Conclusions: OCSs have a considerable effect on whole blood transcriptome. Differential gene expression analysis demonstrates a clear T2-biomarker transcriptomic signature, but no signature was found in association with T2-biomarker-low patients, including those with a high symptom burden., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5/5Ra have beneficial effects on oral corticosteroid (OCS) use and exacerbation frequency. However, how coexisting bronchiectasis affects the response to such treatments is unknown., Objective: To evaluate the real-world effectiveness of anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma and comorbid bronchiectasis on exacerbation frequency and daily maintenance and cumulative OCS dose., Methods: This real-world study evaluated data from 97 adults with severe eosinophilic asthma and computed tomography-confirmed bronchiectasis from the Dutch Severe Asthma Registry, who initiated anti-IL5/5Ra biologics (mepolizumab, reslizumab, and benralizumab) and had follow-up data for 12 months or greater. The analysis was performed for the total population and subgroups with or without maintenance OCS use., Results: Anti-IL-5/5Ra therapy significantly reduced exacerbation frequency in patients with maintenance OCS use as well as in those without it. In the year before biologic initiation, 74.5% of all patients had two or more exacerbations, which decreased to 22.1% in the follow-up year (P < .001). The proportion of patients on maintenance OCS decreased from 47% to 30% (P < .001), and in the OCS-dependent patients (n = 45) maintenance OCS dose decreased from median (interquartile range) of 10.0 mg/d (5-15 mg/d) to 2.5 mg/d (0-5 mg/d) after 1 year (P < .001)., Conclusions: This real-world study shows that anti-IL-5/5Ra therapy reduces exacerbation frequency and daily maintenance as well as the cumulative OCS dose in patients with severe eosinophilic asthma and comorbid bronchiectasis. Although it is an exclusion criterion in phase 3 trials, comorbid bronchiectasis should not preclude anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: With the expanding treatment landscape for asthma, the process of identifying best-fit, individualized management options is becoming increasingly complicated. Understanding patients' preferences can inform shared decision-making between clinicians and patients., Objectives: To examine preferences of adults with asthma for therapeutic and management attributes and determine how these preferences vary among patients., Methods: We conducted an online discrete choice experiment survey in US adults with asthma. Patient preferences were analyzed using logit models. Factors affecting patients' preferences were identified by least absolute shrinkage and selection operator analysis., Results: A total of 1,184 patients completed the survey (60% female; mean [SD] age, 49.2 [15.0] years). Patients most valued fewer asthma attacks requiring urgent health care professional visits, fewer exacerbations requiring oral corticosteroids, and a reduced risk for oral thrush. Higher value was placed on reducing the risk of short-term (oral thrush) versus long-term side effects (diabetes). Patients were willing to increase rescue medication use in exchange for decreasing exacerbations requiring oral corticosteroids and attacks requiring urgent health care professional visits. Patients preferred a single inhaler for rescue and maintenance and least valued asthma action plans. Demographic, socioeconomic, and clinical factors affected patient preferences., Conclusions: Patients sought convenient management options that focused mainly on decreasing the short-term morbidity associated with asthma exacerbations and therapies. Preferences varied by demographics, clinical factors, and socioeconomics. It is important for shared decision-making discussions to include conversations about morbidity and how available therapeutic options align with individual patient preferences., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone., Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS., Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models., Results: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48])., Conclusions: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Biologic therapies such as mepolizumab and benralizumab offer treatment options for severe eosinophilic asthma (SEA), although long-term real-world data on their use are limited., Objectives: To evaluate the impact of benralizumab and mepolizumab treatment among biologic-naive patients with SEA over 36 months and describe the incidence of super-response at 12 and 36 months, identifying potential predictive factors., Methods: We conducted a retrospective, single-center study of patients with SEA who were given mepolizumab or benralizumab from May 2017 to December 2019, and who completed 36 months of therapy. Baseline demographics, comorbidities, and medication use were described. Data on clinical outcomes, including maintenance oral corticosteroid (OCS) use, annual exacerbation rate (AER), mini Asthma Quality of Life Questionnaire, Asthma Control Questionnaire (ACQ-6), and eosinophil count were collected at baseline and at 12 and 36 months. Super-response was evaluated at 12 and 36 months., Results: A total of 81 patients were included. Maintenance OCS use significantly improved from baseline (5.3 mg/d) to 12 months (2.4 mg/d, P < .0001) and 36 months (0.6 mg/d; P < .0001). Annual exacerbation rate decreased from baseline (5.8) to 12 months (0.9; P < .0001) and 36 months (1.2; P < .0001). Mini Asthma Quality of Life Questionnaire, ACQ-6, and eosinophil count significantly improved from baseline to 12 and 36 months. Twenty-nine patients demonstrated super-response at 12 months. Compared with those without a super-response, these patients had better baseline AER (4.7 vs 6.5; P = .009), mini Asthma Quality of Life Questionnaire (3.41 vs 2.54; P = .002), and ACQ-6 (3.38 vs 4.06; P = .03) scores. Most maintained a super-response up to 36 months., Conclusions: Mepolizumab and benralizumab are associated with significant improvements in OCS use, AER, and asthma control in real-world cohorts for up to 36 months, providing insight into long-term use for SEA., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Asthma is the most frequent chronic disease of childhood, affecting up to 20% of children worldwide. The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment. This project aims to summarize the most recent evidence regarding maintenance therapy for asthma in children and adolescents. A multidisciplinary panel of experts was asked clinical questions regarding the treatment of children and adolescents with asthma. Overall, 10 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results showed that the choice of medication depends on the severity of the child's asthma, phenotype, age, preference, and individual factors. In addition to medications, the identification of comorbidities and modifiable factors is crucial to obtaining good control. Asthma in children is heterogeneous, and its evolution varies over time. Since most recommendations for asthma management in childhood are extrapolated from clinical studies performed in adults, more clinical trials specifically designed for young children should be conducted.

Purpose: When first-line chronic rhinosinusitis (CRS) treatment fails, patients can either be treated with oral or injected systemic corticosteroids. Although the EPOS and international guidelines for CRS do not mention injected corticosteroids, it is commonly used by ear, nose, and throat specialists. While the risks of systemic corticosteroids, in general, are known, the pros and cons of injected and oral corticosteroids (OCS) in CRS treatment are unclear., Methods: A systematic review of studies that report the effects and/or side effects of injected and oral corticosteroids in the treatment of CRS was made according to the PRISMA guidelines., Results: Altogether, 48 studies were included, only five studies reported on injected corticosteroids, and five attended with side effects. Three studies found beneficial effects of OCS perioperatively on sinus surgery, while four articles found no effect. Nineteen articles reported that OCS resulted in an improvement in symptoms. Two articles presented a longer-lasting effect of injected corticosteroids than OCS. Three studies reported adverse side effects of systemic corticosteroids, while two studies showed no adverse side effects. One study showed less adrenal suppression after injected corticosteroids compared to OCS. The evidence is not strong but shows a positive effect of systemic corticosteroids that lasts longer with injections., Conclusion: Although systemic corticosteroids are widely used to treat CRS, there is a lack of studies comparing the OCS and injected corticosteroids. The evidence is sparse, however, injected steroids show longer effects with fewer side effects. An RCT study is needed to compare OCS and injected corticosteroids., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: The reboot approach could be an effective treatment option to lower recurrence rates (RRs) in recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). The purpose of this study was to investigate RR, recurrence-free survival (RFS), quality of life (QoL) improvement, and oral corticosteroid (OCS) intake in pluri-operated CRSwNP patients treated with partial reboot surgery., Methods: A consecutive sample of patients with recalcitrant CRSwNP, ineligible for monoclonal antibodies, underwent partial reboot surgery. The 22-item SinoNasal Outcome Test (SNOT-22), Visual Analogue Scales (VAS) scores, OCS intake, and endoscopic Nasal Polyp Score (NPS) were collected pre and postoperatively. The main outcomes were RR and RFS, and comparison of disease-free time with previous endoscopic surgeries., Results: Thirty pluri-operated patients were enrolled. Before the reboot, all had experienced disease recurrence at a mean recurrence time of 8.08 ± 2.83 months after surgery. After reboot, 7 (23.3%) had recurrence at a mean time of 16.67 ± 3.07 months (p = 0.02); none needed additional revision surgery till time of data collection. RR at 12, 18, and 24 months follow-up resulted significantly lower for reboot than other previous surgeries (p = 0.010, p = 0.002, p = 0.016, respectively); RFS difference resulted significant (log-rank test = 4.16; p = 0.04). Differences between pre-and post-operative total and single-items scores of SNOT-22 were significant (p = 0.001), as well as VAS scores (p = 0.001). Before the reboot, 21 patients (70%) took ≥2 OCS courses per year; at the latest follow-up visit, none had taken any course of OCS after reboot., Conclusions: The reboot approach showed lower RR, longer RFS, improved QoL, and zeroing of OCS uptake. Larger samples and longer follow-up studies are needed to assess long-term efficacy and safety of this procedure., Level of Evidence: 4: According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2022. Laryngoscope, 133:1584-1589, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: The goal of this study was to compare health care costs, health care resource utilization, and adverse events associated with sustained oral corticosteroid (OCS) use versus no OCS use in systemic lupus erythematosus., Methods: This retrospective cohort study used claims data (January 1, 2006-July 31, 2019) from patients with systemic lupus erythematosus aged ≥5 years with ≥24 months of continuous enrollment. Health care costs, health care resource utilization, and OCS-related adverse events were assessed. The sustained OCS cohort (defined as ≥12 months of continuous OCS use) was divided into exposure categories based on the number of 6-month classification periods with >5 mg/d OCS (0, 1-2, or 3-4)., Findings: Of the 6234 patients in the sustained OCS use cohort, there were 1587 (25.5%) patients with 0 periods of >5 mg/d OCS use, 2087 (33.5%) patients with 1 to 2 periods of >5 mg/d OCS use, and 2560 (41.1%) patients with 3 to 4 periods of >5 mg/d OCS use; the no OCS use cohort included 7828 patients. Adjusted health care cost differences (95% CIs) were significantly greater for patients with 0, 1 to 2, and 3 to 4 periods of OCS use >5 mg/d versus the no OCS use cohort ($7774 [5426-10,223], $21,738 [18,898-25,321], and $30,119 [26,492-33,774], respectively). A higher proportion of patients in all OCS exposure categories required health care resource utilization (≥99.7% vs 93.4%) and experienced OCS-related adverse events (94.3%-96.8% vs 82.6%) versus the no OCS use cohort, with more periods of OCS use >5 mg/d associated with increased health care resource utilization and adverse events., Implications: Sustained OCS use in systemic lupus erythematosus was associated with high economic burden, health care resource utilization, and OCS-related adverse events. These data highlight the need for health care providers to carefully consider OCS use in systemic lupus erythematosus., Competing Interests: Declaration of Competing Interest Dr Huang and Ms Averell were employees of GSK and held stocks and shares in the company. Dr Huang is an employee of Seagen, Inc. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Analysis Group received research funding from GSK to conduct this study. Mr Bell is an employee of GSK and holds stocks and shares in the company. GSK was involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication., (Copyright © 2023. Published by Elsevier Inc.)

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life., Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions., Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43)., Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Asthma causes various clinical symptoms, including unpredictable severe exacerbations, and even though most patients can achieve a reasonable disease control due to adequate treatment, some patients do not. This study seeks to describe healthcare resource utilization (HCRU) and treatment of asthma and severe asthma patients in Germany., Method: A retrospective claims data analysis has been conducted on adult asthma patients and a subset of patients with severe asthma, identified during July 2017 - June 2018. A proxy was used to identify severe asthma patients based on therapy options recommended within the German treatment guideline for treating these patients. These include (i) biologics, (ii) medium/high-dose inhaled corticosteroids (ICS) in conjunction with LABA/montelukast and antibiotics/oral corticosteroids (OCS), and (iii) long-term OCS therapy. HCRU and treatment of patients were observed during a 1-year follow-up period (July 2018 - June 2019)., Results: The study included 388 932 adult asthma patients (prevalence: 7.90%), with 2.51%-12.88% affected by severe asthma (depending on the definition). 22.60% of all asthma patients experienced hospitalizations (severe asthma: 36.11%). Furthermore, 13.59% received OCS (severe asthma: 39.91%), but only 0.18% (severe asthma: 1.25%) received biologics. Only 23.95% (severe asthma: 41.17%) visited a pulmonologist., Conclusions: A considerable proportion of severe asthma patients receive long-term OCS therapy. However, less than 50% have seen a pulmonologist who would typically seek a change in treatment to avoid the long-term consequences of OCS. To optimize the treatment of severe asthma in Germany, better referral of these patients to specialists is needed and considering potential treatment alternatives.

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy., Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab., Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT., Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT., Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Asthma affects 339 million people worldwide, with an estimated 5-10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS. Despite the risks, research indicates that 40-60% of people with severe asthma are receiving or have received long-term OCS treatment. Although often perceived as a low-cost option, long-term OCS use can result in significant health impairments and costs owing to adverse outcomes and increased utilization of healthcare resources. Alternative treatment methods, such as biologics, may produce cost-saving benefits with a better safety profile. A comprehensive and concerted effort is necessary to tackle the continued reliance on OCS. Accordingly, a threshold for OCS use should be established to help identify patients at risk of OCS-related adverse outcomes. Receiving a total dose of more than 500 mg per year should trigger a review and specialist referral. Changes to national and local policies, following examples from other chronic diseases, will be crucial to achieving this goal. Globally, multiple barriers to change still exist, but specific steps have been identified to help clinicians reduce reliance on OCS. Implementing these changes will result in positive health outcomes for patients and social and economic benefits for societies., (© 2023. The Author(s).)

(1) Background: Corticosteroids are commonly used for a variety of conditions, but their use might come with significant side effects. Self-medication practices increased during the COVID-19 pandemic, potentially favoring corticosteroid misuse. Studies on this topic are lacking, thus we aim to characterize the misuse of corticosteroids in Italy through pharmacists' perspectives and sales reports. (2) Methods: We sent to territorial pharmacists a survey that aimed to investigate corticosteroid misuse before and during the pandemic. In parallel, sales reports of the major oral corticosteroids were obtained from IQVIA. (3) Results: We found that 34.8% of clients demanded systemic corticosteroids without a valid prescription, with a rise to 43.9% during the pandemic ( p < 0.001). Adults and patients suffering from upper airway diseases or obstructive airway diseases most frequently asked for corticosteroids without an appropriate prescription. The greatest increase after the beginning of the pandemic was seen for lung diseases. Although sales of the major oral corticosteroids decreased during the pandemic, sales of those used for COVID-19 increased. (4) Conclusions: Self-medication with corticosteroids is common and might lead to avoidable toxicities. This tendency increased during the pandemic probably because of incorrect beliefs about the inappropriate use of corticosteroids for treating COVID-19 itself. The development of shared strategies between doctors and pharmacists is essential in defining protocols guiding appropriate patient referral in order to minimize corticosteroid misuse.

Context Over the past 60 years, several researchers have conducted extensive studies on the use of dexamethasone to reduce the postoperative complications of lower third molar surgery, namely, pain, edema, and trismus. In this study, we compared the oral and intramuscular methods of dexamethasone administration. Purpose The aim of this research was to assess pain, edema, and trismus in the postoperative period following the surgical removal of the lower third molar using 8 mg of dexamethasone given orally or by intramuscular injection. Method A split-mouth technique was employed for the study, in which each of the two bilaterally impacted mandibular third molars was removed one at a time, separated by at least two weeks. There were 26 participants in this experiment. Two groups were created from the research sample: group A (injection dexamethasone) and group B (tablet dexamethasone). The pain was assessed on the first, second, and third postoperative days. On the first, third, and seventh postoperative days, the parameters, such as edema and trismus, were evaluated. Results As per our study, in terms of edema and trismus, there was less of a statistically significant difference between the two interventions at all time points. While the pain score had a significant difference between both interventions. Conclusion Hence, we conclude that oral dexamethasone is an effective alternative to intramuscular dexamethasone. Oral dexamethasone is comparatively simple, less invasive, painless, and easy for the surgeon and for apprehensive patients, and it offers a cost-effective solution for the suffering often associated with the extraction of impacted lower third molars., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Lakhani et al.)

Background: In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications., Methods: We evaluated the benefit from initiation of ICS administration once daily at school. We retrospectively chose patients from our pediatric pulmonary clinic who had poorly controlled asthma and prescribed ICS daily. For the study period, we examined the number of corticosteroid courses, emergency room visits, hospital admissions, symptom history, and pulmonary function tests., Results: Thirty-four patients who satisfied the inclusion criteria began the intervention. Preintervention, there were a mean number of 2.6 oral corticosteroid courses compared to 2 courses in the year following intervention ( P  = 0.8). Postintervention emergency department visits decreased from a mean of 1.4 to 1.0 ( P  = 0.71), and hospital admissions decreased from 1.23 to 0.57 ( P  = 0.04). There was also a significant increase in forced expiratory volume in 1 second (1.69 vs 1.4 L/sec, P  = 0.02), a decrease in systemic steroid-free days in a year (96 vs 141 days, P  = 0.03), and an increase in symptom-free days postintervention (28 vs 26 days, P  = 0.325)., Conclusion: These findings suggest that ICS administration in schools may help reduce hospital admissions and improve lung function in patients with poorly controlled asthma., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2023 Baylor University Medical Center.)

Background: Frailty is a geriatric syndrome of age-related physiological decline, which is associated with higher mortality and decreased healthy life expectancy, and muscle weakness is one of the presentations of frailty. We investigated an association between lifetime oral corticosteroid (OCS) exposure with frailty and muscle weakness among elderly patients with asthma., Methods: We studied 203 consecutive elderly outpatients with asthma aged ≥60 years old. They were classified into three groups according to their cumulative lifetime OCS dose (lifetime non-users, lower-dose users, and higher-dose users), which was retrospectively estimated from the response to a structured questionnaire. The prevalence of frailty determined by the Kihon Checklist was compared between the three groups. Hand-grip strength, and lean mass index were also measured as markers of muscle strength., Results: Thirty-seven percent of the patients studied were considered frail. Higher cumulative lifetime OCS exposure was associated with a significantly higher prevalence of frailty (33% in lifetime non-users, 59% in lower-dose users, and 68% in higher-dose users; P for trend <0.005). This was also associated with lower hand-grip strength in both sexes (P for trend; 0.012 in men, and 0.020 in women), and lower lean mass index in men (P for trend 0.002). However, current doses of OCS were not significantly associated with these outcomes., Conclusions: Cumulative lifetime OCS exposure was associated with a higher prevalence of frailty and muscle weakness. These findings emphasize the importance of minimizing lifetime OCS exposure for the prolongation of healthy life expectancy in patients with asthma., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: In Australia, the regional prevalence of difficult-to-treat asthma is unknown. We aimed to describe regional variation in difficult-to-treat asthma prevalence and oral corticosteroid (OCS) use., Methods: In this retrospective, observational, longitudinal study using data from March 2018-February 2019 in the NostraData longitudinal database, prescriptions dispensed for obstructive airway disease were processed through a high-level algorithm to identify patients with asthma. Difficult-to-treat asthma was defined by ≥2 high-dosage inhaled corticosteroids plus long-acting beta-agonist prescriptions over 6 months. Patients who additionally received OCS prescriptions sufficient to treat ≥2 exacerbations over 6 months were classified as having uncontrolled difficult-to-treat asthma. Patient-level data were analyzed across 340 geographic areas in Australia to determine regional prevalence of difficult-to-treat asthma, uncontrolled difficult-to-treat asthma, and OCS use., Results: Of 1 851 129 people defined as having asthma, 440 800 (24%) were classified as having difficult-to-treat disease. Of those difficult-to-treat asthma patients, 96 338 (22%) were considered to have uncontrolled disease. Between 29% and 48% of patients had difficult-to-treat asthma in 49 geographic areas, most frequently located in Western Australia. Between 26% and 67% of patients had uncontrolled difficult-to-treat asthma in 29 geographic areas (mostly in Eastern Australia). Overall, a wide variability of asthma severity and control was observed among regions., Conclusions: Despite global and national guidelines, regional differences in the prevalence of difficult-to-treat asthma and uncontrolled difficult-to-treat asthma and OCS use exist in Australia. Understanding these regional variations should inform policy and target management in the areas with the greatest unmet need.

Background: An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking., Objective: The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA., Methods: We conducted a systematic search across standard databases using specific key words until May 13, 2021. We performed a meta-analysis to compare the effectiveness (exacerbations, oral corticosteroid [OCS] use, lung function, and patient-reported asthma control) and safety of pre- and post-omalizumab treatment. Subgroup analyses were performed for treatment duration and underlying disease., Results: In total, 49 studies (n = 267) were included in the qualitative synthesis and 14 case series (n = 186) in the quantitative meta-analysis. Omalizumab treatment significantly reduced the annualized exacerbation rate compared with pretreatment (mean difference, -2.09 [95% CI, -3.07 to -1.11]; P < .01). There was a reduction in OCS use (risk difference, 0.65 [95% CI, 0.46-0.84]; P < .01), an increase in termination of OCS use (risk difference, 0.53 [95% CI, 0.24-0.82]; P < .01), and a reduction in OCS dose (milligrams per day) (mean difference, -14.62 [95% CI, -19.86 to -9.39]; P < .01) in ABPA patients receiving omalizumab. Omalizumab improved FEV 1 % predicted by 11.9% (95% CI, 8.2-15.6; P < .01) and asthma control, and was well-tolerated., Conclusions: Omalizumab treatment reduced exacerbations and OCS use, improved lung function and asthma control in patients with ABPA, and was well-tolerated. The results highlight the potential role of omalizumab in the treatment of ABPA., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV 1 /FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes ( FOXO3 , PTEN , and MAPK3 ) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Background: Although there are currently alternative treatments to the long-term use of oral corticosteroids (OCS) in severe asthma, recent studies show excessive use depending on geography and differences in medical practice. The objective of the study was to describe the differences in OCS use for severe asthma across the Spanish geography., Methods: This is a real-world study using existing databases (year 2019): longitudinal patient database (EMR), based on electronic medical records, and database of pharmacological consumption (Sell-in) in basic healthcare areas. With EMR, the percentage of OCS prescriptions corresponding to patients with severe asthma (ICD-9 "asthma" and prescription of biological treatment and/or high dose of inhaled corticosteroids/long-acting inhaled β2 agonists) was calculated. This percentage was transferred to the OCS consumption of each basic healthcare area as reported in the Sell-in database and a national heat map was created. The estimation of OCS use in patients with severe asthma per 100,000 inhabitants for each region was calculated by grouping basic healthcare areas and the mean OCS use per patient for different regions in Spain was also estimated., Results: Patients with severe asthma in Spain were mostly female (69.6%), with a mean age (SD) of 57.6 years (18.01). Median time (Pc25-Pc75) since asthma diagnosis was 83.1 months (34.65-131.56). Of all patients with OCS prescriptions in 2019 identified in EMR, 4.4% corresponded to patients with severe asthma. Regions with the highest OCS use were Asturias, Andalucía, and Galicia, whereas those with the lowest use were Navarra, Baleares, Madrid and País Vasco. The mean OCS use per patient with severe asthma in 2019 throughout Spain was 1099.85 mg per patient, ranging from 782.99 mg in Navarra to 1432.64 in Asturias., Conclusions: There are geographical differences between Spanish regions with respect to the use of OCS in patients with severe asthma. The national mean consumption of OCS per patient with severe asthma and year is above the limits that indicate good asthma control., (© 2023. The Author(s).)

Purpose: Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA)., Methods: Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®)., Results: A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users)., Conclusion: These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients., Competing Interests: MR, CB, MP, ATR, and ZM report no conflicts of interest in this work. CS, GS and FB are employees of AstraZeneca. JAF reports personal fees from AstraZeneca, Viatris, and GSK; grants and personal fees from Novartis and from Mundipharma, outside the submitted work and is co-founder of MEDIDA, Lda that provided project management services for the study. JCS reports Advisory Board from Boehringer Ingelheim, personal fees and Advisory Board from GSK, grants, personal fees and Advisory Board from AstraZeneca, personal fees and Advisory Board from Bial, non-financial support from Mundipharma, personal fees from Sanofi, Advisory Board from Novartis, outside the submitted work., (© 2022 Romão et al.)

Objective: Conventional inhaler devices have a low efficacy in targeting small airways. Smart nebulizers can be used to increase deposition to small airways by adjusting the flow and depth of each inhalation based on patients 'individual inspiratory capacity. We investigated whether targeting of high dose inhaled corticosteroids (ICS) to small airways with a smart nebulizer could reduce exacerbation rate in children with severe asthma (SA)., Methods: We conducted a retrospective study in children with SA using a smart nebulizer (Akita® Jet nebulizer) for the administration of high dose ICS in our outpatient clinic at the Erasmus MC - Sophia Children's Hospital. Clinical data before and after start of treatment were collected. The primary outcome was exacerbation rate, defined as: number of asthma exacerbations for which oral corticosteroid courses (OCS) were prescribed. The exacerbation rate 1 year before treatment was compared with the exacerbation rate 1 year after start of treatment. Secondary outcomes were changes in spirometry parameters, hospital admissions and medication use., Results: Data on OCS use was available for 28/31 patients. Median number of asthma exacerbations requiring OCS courses 1 year before decreased from 2 (interquartile range(IQR) 2) to 0.5 (IQR 3) 1 year after treatment ( p  = 0.021). Hospital admission decreased from 1 (IQR 3) to 0 (IQR 1)( p  = 0.028). FEV1, FEF 25-75 and FEF 75 were not significantly improved after one year of treatment with the smart nebulizer ( p  = 0.191; p  = 0.248; p  = 0.572)., Conclusion: Targeting small airways with high dose ICS using a smart nebulizer resulted in a significant reduction in exacerbations requiring OCS after one year of treatment.