Asthma severity: the patient's point of view.

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.

A Distinct Instance of Palindromic Rheumatism Disguised as Polymyalgia Rheumatica.

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.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts.

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 ß2 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.

Dupilumab Improves Facial Pain and Reduces Rescue Treatments in Patients with CRSwNP and Recalcitrant Frontal Sinusitis.

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.

Exploring Clinical Remission in Moderate Asthma - Perspectives from Asia, the Middle East, and South America.

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.

Healthcare Resource Utilization Associated with Intermittent Oral Corticosteroid Prescribing Patterns in Asthma.

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.

Tezepelumab improved chronic eosinophilic pneumonia in severe asthma patients with liver cirrhosis.

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.

Oral Prescription Management.

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.

Expert consensus on oral corticosteroids stewardship for the treatment of severe asthma in the Middle East and Africa.

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.

Asthma management, focused on the use of oral corticosteroids: the opinions of Italian asthmatic patients.

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.

Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT.

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.

Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

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.

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis.

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.

Neuroretinitis following typhoid fever in a 55-year-old female: Case report

@#Neuroretinitis (NR) is an inflammation of the optic nerve and the neural retina. NR is diagnosed clinically, and it is characterized by blurring of vision (BOV), optic disc swelling, and macular star exudates. Spontaneous resolution of NR is possible, but corticosteroids help in hastening recovery. Rarely, Salmonella typhi infection may produce an immune-mediated reaction that can cause NR. Immune-mediated retinitis occurs 3 to 6 weeks after the febrile period of a typhoid infection. We present the case of a 55-year-old female with a two-week history of painless, unilateral BOV occurring five weeks after the initial febrile episode of a typhoid infection. A diagnosis of NR was made after fundus examination on the affected eye showed optic disc edema and macular star exudates. An eight-week course of corticosteroid treatment afforded partial resolution of the disc edema and significant reduction in the macular exudates, and improved the patient’s vision after six months.