Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study.

INTRODUCTION: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. METHODS: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. RESULTS: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). CONCLUSION: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

Introduction: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. Methods: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients' demographic and clinical characteristics were further analyzed depending on the severity of the reaction. Results: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25-75] age: 42 [33-52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1-7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1-6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5-17.0); p = 0.011, OR (CI) = 10.3 (1.6-63.3)]. Conclusion: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment

Abstract Background: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. Objectives: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. Methods: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. Results: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). Study limitations: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. Conclusions: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Evaluation of the Clinical Features and Laboratory Data of Patients with Severe Eosinophilic Asthma Classified as Super-Responders, Partial Responders, or Nonresponders to Mepolizumab Treatment: A Real-Life Study.

INTRODUCTION: Mepolizumab is a treatment option in patients with severe eosinophilic asthma, which inhibits interleukin-5. The aim of this study was to evaluate the clinical features and laboratory data of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. METHODS: In this retrospective real-life study, the clinical features and laboratory data were compared between groups of patients with severe eosinophilic asthma who were classified as super-responders, partial responders, or nonresponders to mepolizumab treatment. RESULTS: Evaluation was made of a total of 55 patients, comprising 17 (30.9%) males and 38 (69.1%) females with a mean age of 51.28 ± 14.32 years. All the patients were receiving mepolizumab treatment for severe eosinophilic asthma, with 17 (30.9%) patients evaluated as super-responders, 26 (47.3%) as partial responders, and 12 (21.8%) as nonresponders. After mepolizumab treatment, there was a statistically significant decrease in asthma exacerbations, the number of oral corticosteroids (OCSs) used, the rate of hospitalization due to asthma attacks, and the eosinophil count (cells/µL) (p < 0.001, p < 0.001, p < 0.001, and <0.001, respectively). A statistically significant increase was determined in the forced expiratory volume in 1 s (FEV1) value (p = 0.010) and asthma control test (ACT) score (p < 0.001) after mepolizumab treatment. The baseline eosinophil count, eosinophil/lymphocyte ratio and FEV1 (%) values were significantly higher in the super-responder and partial responder groups (p < 0.001, p = 0.002, and p = 0.002, respectively). The baseline ACT score and the rate of chronic sinusitis with nasal polyps were significantly higher in the partial responder group (p = 0.004, p = 0.015, respectively). The rate of regular OCS use before mepolizumab treatment was significantly higher in the nonresponder group (p = 0.049). As a result of the receiver operating characteristics curve analysis, the blood eosinophil count (area under the curve [AUC]: 0.967, p < 0.001), eosinophil/lymphocyte ratio (AUC: 0.921, p < 0.001), and FEV1 (%) (AUC: 0.828, p = 0.002) were found to have diagnostic value in predicting the response to mepolizumab treatment in patients with severe eosinophilic asthma. CONCLUSION: Baseline eosinophil count, eosinophil/lymphocyte ratio, and FEV1 (%) were found to be important predictors of response to mepolizumab treatment. Further studies are needed to define the characterization of mepolizumab responders in the real world.

Evaluation of the clinical features and laboratory data of patients with severe asthma classified as super-responder or non super-responder to omalizumab treatment: a single-center real-life study.

INTRODUCTION: Omalizumab is used for the treatment of severe allergic asthma. OBJECTIVE: The aim of this study was to evaluate the clinical features and laboratory data of patients with severe allergic asthma classified as super-responder or non super-responder to omalizumab. METHODS: Comparisons were made of the laboratory data and clinical features of patients with severe allergic asthma. Patients who had no asthma exacerbation, no oral corticosteroid (OCS) use, asthma control test (ACT) score >20 and forced expiratory volume in 1 s (FEV1) >80% were considered super-responder after omalizumab. RESULTS: A total of 90 patients were included in the study, comprising 19 (21.1%) males. The age at onset of asthma, allergic rhinitis rate, number of endoscopic sinus surgeries (ESS), intranasal corticosteroid (INS) use, baseline FEV 1 (%) and ACT score were significantly higher in the omalizumab super-responder group (p = 0.013, p = 0.015, p = 0.002, p = 0.001, p = 0.001 and p < 0.001, respectively). The duration of asthma, rate of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), regular use of OCS, baseline eosinophil count and eosinophil-to-lymphocyte ratio were significantly higher in the omalizumab non super-responder group (p = 0.015, p < 0.001, p = 0.004, p < 0.001 and p < 0.001, respectively). Blood eosinophil count (AUC: 0.187, p < 0.001), eosinophil-to-lymphocyte ratio (AUC: 0.150, p < 0.001) and FEV1 (%) (AUC:0.779, p = 0.001) were determined to have diagnostic value in predicting the treatment response to omalizumab of patients with severe allergic asthma. CONCLUSION: High-blood eosinophil levels, CRSwNP and low pretreatment lung capacity may affect omalizumab treatment response in patients with severe allergic asthma. These results should be supported by further multicenter real-life studies.

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic.

BACKGROUND: Mast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. METHODS: Mental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV-19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. RESULTS: The mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. CONCLUSIONS: Fear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastocytosis.

BACKGROUND: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. OBJECTIVE: To investigate the endothelial function in mastocytosis by flow-mediated dilatation (FMD) and biomarkers related to vascular endothelia and to evaluate its relationship with the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). METHODS: A total of 49 patients with mastocytosis and 25 healthy controls (HCs) were included. The FMD and CIMT during transthoracic echocardiography biomarkers including endocan, endothelin-1, and vascular endothelial growth factor (VEGF) were measured in the sera of participants. Tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein were determined as inflammatory biomarkers. RESULTS: The mean FMD % was lower in the patients than HCs (11.26% ± 5.85% vs 17.84% ± 5.27% P < .001) and was the lowest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group among the patients (P = .03). The median value of VEGF was considerably higher in patients than HCs (73.30 pg/mL; minimum-maximum 32.46-295.29 pg/mL vs 46.64 pg/mL; minimum-maximum, 11.09-99.86 pg/mL; P = .001) and it was the highest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group (P = .01). The FMD was inversely correlated with endocan (r = -0.390; P = .006), endothelin-1 (r = -0.363; P = .01) and VEGF (r = -0.402; P = .004) but there were no correlations between FMD and tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein. No differences in CIMT values between patients and HCs and no correlation between CIMT and the biomarkers were observed. CONCLUSION: Endothelial dysfunction in mastocytosis becomes evident with decreased FMD and elevated serum VEGF in the absence of atherosclerosis or systemic inflammation and is related to disease severity.

Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?

BACKGROUND: C3 glomerulopathy (C3GP) is a recently identified and described disease that has a high risk of progressing into end-stage renal disease. We aimed to evaluate the effects of various immunosuppressive regimens on C3GP progression because there are conflicting data on the treatment modalities. METHODS: In this retrospective study of 66 patients with C3GP, 27 patients received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based treatment (prednisolone or cyclophosphamide), and 16 received conservative care. The study groups were compared with each other with specific focus on primary outcomes defined as (1) kidney failure and (2) estimated glomerular filtration rate (eGFR) decline ≥50% from the baseline value. RESULTS: Overall, 17 (25.8%) patients reached the primary outcome after a median period of 28 months. The number of patients who reached the primary outcome were similar among the study groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p = 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p = 0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR 1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002) predicted the primary outcome. CONCLUSION: Although patients receiving immunosuppressive treatments had higher proteinuria and lower serum albumin at baseline, there were no differences between these patients and those receiving conservative care alone in proteinuria remission or in the decline of renal function. Younger age, higher proteinuria, lower eGFR, and the presence of crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no remission of proteinuria predicted the progression of kidney disease.