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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Abstract 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.

Trung N Tran,1 Heath Heatley,2 Arnaud Bourdin,3 Andrew Menzies-Gow,4,5 David J Jackson,6 Ekaterina Maslova,5 Jatin Chapaneri,5 William Henley,2,7 Victoria Carter,2 Jeffrey Shi Kai Chan,2 Cono Ariti,2 John Haughney,8,9 David Price2,9 1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Department of Respiratory Diseases, PhyMedExp, University of Montpellier, Montpellier, France; 4Royal Brompton & Harefield Hospitals and School of Immunology & Microbial Sciences, King’s College London, London, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Guy’s Severe Asthma Centre, Guy’s and St Thomas’ Hospitals, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7Department of Health and Community Sciences University of Exeter Medical School, Exeter, UK; 8NHS Clinical Research Facilities, Glasgow, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgPurpose: 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.Keywords: asthma, costs, healthcare resource utilization, intermittent, oral corticosteroids

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of severe asthma in South Korea and the challenges associated with oral corticosteroid (OCS) use for managing severe asthma. The Korean Severe Asthma Registry (KoSAR) provides valuable insights into patients with severe asthma in Korea, highlighting the need for OCS stewardship to minimize risks associated with long-term OCS use. The implementation of OCS stewardship involves strategies such as biologics as alternatives to OCS, stepwise OCS tapering protocols, and multidisciplinary collaboration among healthcare providers. By adopting these approaches, the management of severe asthma in South Korea can be improved, leading to better patient outcomes and quality of life. [Extracted from the article]

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.

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. [ABSTRACT FROM AUTHOR]

Michael Bogart,1 Guillaume Germain,2 François Laliberté,2 Malena Mahendran,2 Mei Sheng Duh,3 Kristi DiRocco,4 Stephen G Noorduyn,5,6 Rosirene Paczkowski,7 Ronald Balkissoon8 1U.S. Value Evidence and Outcomes, R&D U.S., GSK, Research Triangle Park, Durham, NC, USA; 2Groupe d’Analyse, Ltée, Montréal, QC, Canada; 3Analysis Group, Inc., Boston, MA, USA; 4U.S. Medical Affairs, GSK, Collegeville, PA, USA; 5Global Value Evidence and Outcomes, GSK, Mississauga, ON, Canada; 6Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; 7Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 8National Jewish Health, Denver, CO, USACorrespondence: Kristi DiRocco, U.S. Medical Affairs, GSK, Collegeville, PA, USA, Tel +1 610-412-7175, Email kristi.k.dirocco@gsk.comPurpose: 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 β2-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 β2-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.Keywords: oral corticosteroids, rescue medication use, asthma control, FF/UMEC/VI, asthma exacerbations

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. We describe two cases of uncontrolled severe asthma characterized by systemic clinical consequences of prolonged OCS use, such as diabetes, weight gain, and osteoporosis. 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. Dupilumab was able to control both the inflammatory-induced "airway remodeling" as well as the OCS-induced "patient remodeling". [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Michael Bogart,1 Carl B Abbott,2 Mohan Bangalore,3 Donna McMorrow,4 Elizabeth R Packnett,4 Kristi DiRocco3 1US Value Evidence and Outcomes, GSK, Durham, NC, USA; 2US Medical Affairs, GSK, Durham, NC, USA; 3US Medical Affairs, GSK, Collegeville, PA, USA; 4Merative, Ann Arbor, MI, USACorrespondence: Kristi DiRocco, US Medical Affairs, GSK, 1250 S. Collegeville Road, Collegeville, PA 19426, USA, Tel +1 610-412-7175, Email kristi.k.dirocco@gsk.comPurpose: 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.Plain Language Summary: Oral corticosteroids (OCS) are drugs that are often used in the short term to treat chronic obstructive pulmonary disease (COPD) exacerbations. Long-term use of OCS is not recommended as this can increase the risk of pneumonia and death. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) is a maintenance treatment for COPD, which combines three drugs into one inhaler. In this study, we investigated OCS use before and after starting FF/UMEC/VI. We found that there were 32.2% less patients with an OCS claim in the year after starting FF/UMEC/VI compared with the year before. In addition, 30.0% of patients reduced their daily OCS dose by 90– 100%. We also looked at how often patients were using healthcare services because of their COPD after starting FF/UMEC/VI, and how much this cost. We found that there were fewer inpatient stays, emergency room visits, and doctor’s office visits due to COPD in the year after starting FF/UMEC/VI treatment compared with the year before. Overall, these results show that patients who use OCS every day may be able to reduce their dose after starting FF/UMEC/VI treatment, which may avoid some of the potential side effects of OCS.Keywords: COPD, FF/UMEC/VI, oral corticosteroids

Breda Cushen,1,&ast; Mariko Siyue Koh,2,&ast; Trung N Tran,3 Neil Martin,3,4 Ruth Murray,5 Thendral Uthaman,6 Celine Yun Yi Goh,5,6 Rebecca Vella,7 Neva Eleangovan,5,6 Lakmini Bulathsinhala,5,6 Jorge F Maspero,8,9 Matthew J Peters,10 Florence Schleich,11 Paulo Pitrez,12 George Christoff,13 Mohsen Sadatsafavi,14 Carlos A Torres-Duque,15,16 Celeste Porsbjerg,17 Alan Altraja,18 Lauri Lehtimäki,19 Arnaud Bourdin,20 Christian Taube,21 Nikolaos G Papadopoulos,22,23 Csoma Zsuzsanna,24 Unnur Björnsdóttir,25 Sundeep Salvi,26 Enrico Heffler,27 Takashi Iwanaga,28 Mona al-Ahmad,29 Désirée Larenas-Linnemann,30 Job FM van Boven,31 Bernt Bøgvald Aarli,32,33 Piotr Kuna,34 Cláudia Chaves Loureiro,35,36 Riyad Al-lehebi,37 Jae Ha Lee,38 Nuria Marina,39 Leif Bjermer,40 Chau-Chyun Sheu,41,42 Bassam Mahboub,43 John Busby,44 Andrew Menzies-Gow,45 Eileen Wang,46 David B Price5,6,47 On behalf of ISAR Inventory Study Group1Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland; 2Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Respiratory Medicine, University of Leicester, Leicester, UK; 5Optimum Patient Care Global, Cambridge, UK; 6Observational Pragmatic Research Institute, Singapore, Singapore; 7Optimum Patient Care, Brisbane, Queensland, Australia; 8Clinical Research for Allergy and Respiratory Medicine, CIDEA Foundation, Buenos Aires, Argentina; 9University Career of Specialists in Allergy and Clinical Immunology at the Buenos Aires University School of Medicine, Buenos Aires, Argentina; 10Department of Thoracic Medicine, Concord Hospital, Sydney, Australia; 11CHU Sart-Tilman, GIGA I3, University of Liege, Liège, Wallonia, Belgium; 12Pulmonology Division, Hospital Santa Casa de Porto Alegre, Porto Alegre, Brazil; 13Faculty of Public Health, Medical University, Sofia, Bulgaria; 14Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada; 15CINEUMO, Respiratory Research Center, Fundación Neumológica Colombiana, Bogotá, Colombia; 16Universidad de La Sabana, Chia, Colombia; 17Department of Respiratory Medicine and Infectious Diseases, Research Unit, Bispebjerg Hospital, Copenhagen, Denmark; 18Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 19Allergy Centre, Tampere University Hospital, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 20PhyMedExp, Univ Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France; 21Department of Pulmonary Medicine, University Medical Center Essen-Ruhrlandklinik, Essen, Germany; 22Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 23Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 24Asthma Outpatient Clinic, National Koranyi Institute for Pulmonology, Budapest, Hungary; 25Department of Allergy and Respiratory Medicine, University Hospital, Reykjavik, Iceland; 26Pulmocare Research and Education Foundation, Pune, India; 27Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; 28Kindai University Hospital, Osakasayama, Japan; 29Microbiology Department, College of Medicine, Kuwait University, Kuwait, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 30Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 31University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Department of Clinical Pharmacy & Pharmacology, Groningen, the Netherlands; 32Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway; 33Department of Clinical Science, University of Bergen, Bergen, Norway; 34Division of Internal Medicine Asthma and Allergy, Medical University of Lodz, Lodz, Poland; 35Pneumology Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 36Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 37Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia, Alfaisal University, Riyadh, Saudi Arabia; 38Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; 39Pneumology Service, Biocruces, Cruces University Hospital, Barakaldo, Spain; 40Respiratory Medicine and Allergology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; 41Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 42Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 43Rashid Hospital, Dubai Health Authority (DHA), Dubai, United Arab Emirates; 44Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK; 45Lung Division, Royal Brompton & Harefield Hospital, London, UK; 46Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Health and University of Colorado School of Medicine, Denver and Aurora, CO, USA; 47Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, UK&ast;These authors contributed equally to this workCorrespondence: David B Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAim: 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.Keywords: Asia-Pacific, biologics, COVID-19, Europe, ISAR, International Severe Asthma Registry, oral corticosteroids, Registry, Middle East, Severe Asthma, Latin America, USA

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. [ABSTRACT FROM AUTHOR]

Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

BackgroundThere is limited information regarding the impact of dose and gestational timing of oral corticosteroid (OCS) use on preterm birth (PTB), especially among women with asthma.ObjectivesTo evaluate OCS dose and timing on PTB for asthma and, as a comparison, systemic lupus erythematosus (SLE).MethodsWe used health care data from California Medicaid enrollees linked to birth certificates (2007-2013), identifying women with asthma (n = 22,084) and SLE (n = 1174). We estimated risk ratios (RR) for OCS cumulative dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after day 139.ResultsFor asthma, PTB risk was 14.0% for no OCS exposure and 14.3%, 16.8%, 20.5%, and 32.7% in low, medium, medium-high, and high cumulative dose trajectory groups, respectively, during the first 139 days. The high-dose group remained associated with PTB after adjustment (adjusted RR [aRR]: 1.46; 95% confidence interval [CI]: 1.00, 2.15). OCS dose after day 139 was not clearly associated with PTB, nor were controller medications. For SLE, PTB risk for no OCS exposure was 24.9%, and it was 39.1% in low- and 61.2% in high-dose trajectory groups. aRR were 1.80 (95% CI: 1.34, 2.40) for high and 1.24 (95% CI: 0.97, 1.58) for low groups. Only prednisone equivalent dose >20 mg/day after day 139 was associated with increased PTB (adjusted HR: 2.54; 95% CI: 1.60, 4.03).ConclusionsFor asthma, higher OCS doses early in pregnancy, but not later, were associated with increased PTB. For SLE, higher doses early and later in pregnancy were associated with PTB.

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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications. 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. 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). These findings suggest that ICS administration in schools may help reduce hospital admissions and improve lung function in patients with poorly controlled asthma. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA.MethodsPregnant women in the MotherToBaby Pregnancy Studies (2003-2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139.ResultsPTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas

Abstract 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.

Mariana Romão,1 Carolina Bulhosa,1 Zilda Mendes,1 Catarina Sousa,2 Graça Silva,2 Mariana Pereira,3 Filipa Bernardo,2 António Teixeira Rodrigues,1,4 João A Fonseca,3,5,6 Jaime Correia de Sousa4 1Centre for Health Evaluation & Research/Infosaude (CEFAR/IS), National Association of Pharmacies (ANF), Lisbon, Portugal; 2Medical Department, AstraZeneca, Barcarena, Portugal; 3MEDIDA – Medicina, Educação, Investigação, Desenvolvimento e Avaliação, Porto, Portugal; 4Life and Health Sciences Research Institute (ICVS), PT Government Associate Laboratory, School of Medicine, University of Minho, Braga, Portugal; 5Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Porto, Portugal; 6CUF Allergy Unit, Porto Hospital and Institute, Porto, PortugalCorrespondence: Mariana Romão, Centre for Health Evaluation & Research/Infosaude (CEFAR/IS), National Association of Pharmacies (ANF), Rua Marechal Saldanha 1, Lisboa, 1249-069, Portugal, Email mariana.romao@anf.ptPurpose: 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.Keywords: asthma, ICS/LABA, oral corticosteroids, asthma control, CARAT, COVID-19

(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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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 FEV1/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Infantile hemangioma (IH) is the most common benign tumor in infancy. Oral corticosteroids (OCs) still have an important role in the treatment of complex IH. In the present study, we provide our experience of oral propranolol + OCs treatment for IH. Materials and Methods: This was a retrospective cohort study of 26 IHs treated with propranolol, either alone or in combination with OCs, at the National Institute of Pediatrics, Mexico. Information on clinical and demographic data was collected. Data were summarized as mean (standard deviation) or median (minimum, maximum) or frequencies and proportions as needed. Comparative analysis between the group only treated with propranolol and the group treated with propranolol plus OCs was performed with Fisher's exact test or Mann-Whitney C-tests. Results: All of our patients had a positive response to treatment. The comparison between both groups showed that the maximum and mean propranolol doses were significantly lower in the group of patients receiving combined treatment. Conclusions: Our findings support that the use of propranolol plus corticosteroids in IH allows the use of lower doses of both drugs for longer periods with less risk of adverse effects and fewer or no relapses. [ABSTRACT FROM AUTHOR]

Objective. It is unclear whether Benralizumab effectiveness in severe eosinophilic asthma can be influenced by nasal polyposis (NP) or allergic status associations. We evaluated whether Benralizumab long-term efficacy in asthma outcomes could be different in subjects with atopy (SAEA) compared to the effectiveness in those without allergies (SNAEA) and in individuals with NP compared to those without NP. Methods. This observational retrospective study considered 95 consecutive patients divided into allergic (SAEA; n:65[68.4%]; skin prick tests positive [SPT] and/or IgE values ≥100 UI/mL), and non-allergic (SNAEA; n:30[31.6%], SPT negative and normal IgE levels<100 UI/ mL). Overall population was also divided into two groups according to NP presence (NP+:39[41%] and NP-:56[59%]). Benralizumab treatment mean was19.7±7.2 months (range 12-35). Results. No differences in Benralizumab effectiveness were found in asthma outcomes in patients with/without NP. SNOT-22 improvement was higher in NP+ (-22±24) compared to NP- groups (6.33±15.5;p=0.055). FEV1 (16.33±19.22%), ACT(7.45±3.95) increases and frequency of SABA use (3.37±4.99) reduction were higher in SAEA compared to what obtained in non-allergic subjects (FEV1:8.15±15.6%,p=0.043; ACT:4.89±3.57,p=0.005; SABA use:- 1.16±1.84;p=0.015). 93.8% of SAEA patients whereas only 72.2% of SNAEA individuals reduced OC doses at least half after Benralizumab (p=0.035). These results were partially confirmed by linear regression models showing associations between allergic status and FEV1, ACT and SABA use changes (β=8.37;p=0.048, β=2.056;p=0.033 and β=- 2.184;p=0.042 respectively). Conclusion. Benralizumab effectiveness in asthma appears to be independent of NP presence. The allergic eosinophilic disease, compared to just eosinophilic asthma, may be a more severe phenotype. Benralizumab may have greater efficacy in SAEA on some outcomes. [ABSTRACT FROM AUTHOR]

Francesco Menzella,1 Matteo Fontana,1 Marco Contoli,2 Patrizia Ruggiero,1 Carla Galeone,1 Silvia Capobelli,1 Anna Simonazzi,1 Chiara Catellani,1 Chiara Scelfo,1 Claudia Castagnetti,1 Francesco Livrieri,1 Nicola Facciolongo1 1Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy; 2Respiratory Section, Department of Translational Medicine, University of Ferrara, Ferrara, ItalyCorrespondence: Francesco Menzella, Pulmonology Unit, Arcispedale Santa Maria Nuova, Azienda USL – IRCCS di Reggio Emilia, Reggio Emilia, Italy, Tel +39 0522 296073, Email fmenzella@gmail.comPurpose: Treatment of severe asthma has made great strides thanks to rapid progress in understanding immune response and inflammatory pathways. This led to the advent of the first biologic for severe allergic asthma (SAA), omalizumab. Although the long-term efficacy and safety of omalizumab has been confirmed, increasingly longer follow-up data can further reinforce this evidence and potentially provide new ones, for example on any loss of efficacy or the appearance of unexpected side effects. This study reports omalizumab treatment-related outcomes after 16 years of follow-up.Patients and Methods: In this real-life retrospective study, an extension of a previous 9-year follow-up study on patients initially recruited in a clinical trial, we enrolled 8 adult patients with SAA followed-up from November 2005 to December 2021. Study subjects were selected based on omalizumab eligibility criteria.Results: Exacerbation rate significantly decreased from 3.6 ± 2.1 events in year before index date to 0.1 ± 0.4 after 32 weeks of treatment (p < 0.0001). Mean annual number of mild-to-moderate exacerbations at 16 years was 0.88 compared with 1.8 in the year before the index date and 1.1 at 32 weeks. No hospitalizations were documented during the 16-year follow-up compared to 0.3 hospitalizations/patient in the year before the index date. Respiratory function also progressively and significantly improved. Regarding patient-reported outcomes (PROs), The AQLQ and ACT significantly improved from baseline throughout the follow-up, particularly up to 9 years of follow-up. During the study, an overall reduction in doses of asthma medications was observed, with a significant OCS-sparing effect.Conclusion: Our study, the longest clinical follow-up on patients treated with anti-IgE, confirms and amplifies the results of the studies carried out so far, as they are maintained over a very long interval of time without drops in efficacy without any type of side effect.Keywords: severe allergic asthma, biologics, omalizumab, exacerbations, side effects, oral corticosteroids

ABSTRACTPurpose 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.

Oral corticosteroids (OCS) are often prescribed to patients with asthma that remains uncontrolled with maintenance therapy. We performed a real-world analysis to describe the geographic distributions of patients with asthma and OCS dispensed in Nordic countries. This observational, retrospective study examined patient-level data from nationally prescribed drug registries from January to December 2018 for individuals aged ≥12 years in Denmark, Finland, and Sweden. Using an algorithm based on asthma treatment combinations defined by the Global Initiative for Asthma (GINA), we identified patients with asthma, those on GINA Step 4–5 treatments, and those being dispensed ≥2 courses of OCS and determined volumes of OCS dispensed to these patients over the 1-year analysis period. Data were plotted geographically within each country using colour-coded heat maps. The overall asthma prevalence rates were 7.4% in Denmark, 11.6% in Finland, and 8.1% in Sweden. In Denmark, Finland, and Sweden, respectively, the frequencies of patients on GINA Step 4–5 treatments were 19%, 15%, and 16%; among whom 10%, 23%, and 5% received ≥2 courses of OCS. The rates of patients on GINA Step 4–5 treatments who were dispensed OCS in each country were 23%, 30%, and 46%, of which 22%, 17%, and 10% were dispensed doses averaging ≥5 mg/day over the year. Heat maps revealed considerable heterogeneity in geographic densities of patients with asthma and OCS claims within each country. Taken together, these results demonstrate regional variations in estimated asthma severity, control, and OCS dispensed within and between countries. Patterns of medication use suggest that a high proportion of patients in Denmark, Finland, and Sweden are on GINA Step 4–5 treatments, many of whom are dispensed OCS; this poses a considerable corticosteroid burden to these patients. Geographic differences in medication use within and between Nordic countries may reflect variations in population characteristics and/or treatment approaches.

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). 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. 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, FEF25-75 and FEF75 were not significantly improved after one year of treatment with the smart nebulizer (p = 0.191; p = 0.248; p = 0.572). 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Long-term efficacy of Benralizumab in real life is not clearly known. We assessed the long-term effectiveness persistence to anti-IL-5R treatment in a group of severe eosinophilic asthmatics. PATIENTS AND METHODS: We retrospectively analyzed 95 individuals affected by severe asthma (36 males = 37.9%; mean age 58.1 ± 12.2) treated with Benralizumab (mean time 19.7 ± 7.2 months, range 12-35). Outcomes were evaluated at the beginning and at the end of patients' treatment periods. RESULTS: Mean baseline blood eosinophils were 897.5 ± 720.1 cells/µL (11 ± 5.6%) decreasing to 7.4 ± 20.6 cells/µL (0.97 ± 0.26%; p < 0.0001) a fter B enralizumab. F ENO l ikewise decreased from 63.9 ± 68.4 to 28.4 ± 23.6 ppb, while FEV1% significantly improved (p < 0.0001). Mean FEF25-75 also increased from 45.8 ± 24.6% to 60.7 ± 24.6%, whereas RAW dropped from 202.15 ± 109.6% to 135.2 ± 54.75% (p < 0.0001). Also, lung volumes greatly decreased. ACT/ACQ significantly improved, while exacerbations number fell from 4.1 ± 2.4, before anti-IL-5R, to 0.33 ± 0.77, after treatment (p < 0.0001). Rhinitis severity levels and SNOT-22 also changed favorably. Patients that took long-term OCs were 71.6% before treatment, decreasing to 23.2% after Benralizumab (p < 0.0001), with an OCs dose reduction from 14.8 ± 8.9 to 1.45 ± 2.8 mg/day (p < 0.0001). 51.6% of subjects used SABA as needed before Benralizumab, falling to 4.2% after treatment. Several patients showed a reduction of ICS doses, SAEuropean BA use and maintenance therapy step-down. Clinical/biological response with anti-IL-5R remained constant or even improved in terms of exacerbations or maintenance therapy reductions over time. On the contrary, FEF25-75% improvement slowed down in the long-term. No relationship was found between baseline blood eosinophil number and therapeutic response. CONCLUSIONS: Long-term Benralizumab effectiveness persistence in all outcomes in real life was confirmed. [ABSTRACT FROM AUTHOR]

Objectives To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. Methods By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006–18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. Results We found increased aOR of PTB [1.92 (1.56–2.35)] and SGA [1.93 (1.45–2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52–7.55) for PTB and 3.90 (1.46–10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94–4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66–2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. Conclusion During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment. [ABSTRACT FROM AUTHOR]

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: 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.)