Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. PATIENTS AND METHODS: We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3. RESULTS: Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268-4501) occurring at 13 weeks (IQR 4-36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. CONCLUSION: These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study.

BACKGROUND: The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. METHODS: ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. RESULTS: Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430-890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: - 94.9%; severe AER: - 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: - 95.9%; severe AER: - 97.5%) and bio-experienced patients (any AER: - 92.4%; severe AER: - 94.0%). CONCLUSIONS: Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients' eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04272463.

Basal Tryptase High Levels Associated with a History of Arterial Hypertension and Hypercholesterolemia Represent Risk Factors for Severe Anaphylaxis in Hymenoptera Venom-Allergic Subjects over 50 Years Old.

INTRODUCTION: Allergy to Hymenoptera venom (HV) may lead to life-threatening anaphylaxis. Some of the factors influencing the symptom's severity are still undetermined. The aim of this study was to identify the clinical aspects associated with the most severe reactions in a population with HV allergy, by comparing clinical and immunochemical biomarkers between patients with previous local large reactions (LLRs) and systemic reactions (SRs). METHODS: We selected adult patients with a history of HV allergy, with positive diagnostic tests and a correlation with one single Hymenoptera species. Age, gender, atopy, serum basal tryptase (sBT) value, total IgE, venom-specific IgE, history of hypertension, cardiovascular diseases, and hypercholesterolemia were compared between patients with previous LLRs and SRs. RESULTS: 460 adult patients (381 SRs, 79 LLRs) were included. Age (p = 0.0097), male gender (p < 0.0001), arterial hypertension (p = 0.046), hypercholesterolemia (p = 0.009), and higher sBT levels (p = 0.0004) were significantly associated with severe reactions as independent variables. Moreover, considering the previous variables as risk factors, there was a significant and progressive increase in the odds of being Mueller III + IV as the number of positive variables increased. Patients with sBT ≥6.4 ng/mL adjusted for any of the positive variables had increased the risk of Mueller grade IV reaction (p < 0.0001). CONCLUSION: According to our results, older age, male gender, arterial hypertension, hypercholesterolemia, and increased levels of sBT ≥6.4 ng/mL are risk factors for severe anaphylaxis to HV in adults. Atopy and allergic asthma do not increase the risk of HV-induced SRs.

Role of Multiple Comorbidities and Therapies in Conditioning the Clinical Severity of DRESS: A Mono-Center Retrospective Study of 25 Cases.

DRESS/DiHS is a complex and potentially fatal drug reaction. Little is known about risk factors and elements that can help to identify patients with a severe reaction early. The aim of the study was to investigate those factors favoring the disease and its severity by analyzing the clinical conditions and therapies preceding the reaction. We conducted a retrospective analysis on patients admitted to our center between 2010 and 2020 who were discharged with a diagnosis of DRESS. We used the RegiSCAR diagnostic criteria. We defined the severity of DRESS using the criteria of Mizukawa et al. We included 25 patients (15 females) with a median age of 66 years. Skin involvement, eosinophilia, and liver injury were the most important aspects. Allopurinol was found to be the most involved drug. Reaction severity was significantly associated with the number of daily medications (p=0.0067) and an age of at least 68 years (p=0.013). In addition, 75% of severe cases had at least three comorbidities in history, and most of the severe cases were female. In our study the advanced age, the high number of comorbidities and home therapies, and the inflammatory state were found to be predisposing elements to the development of the disease and its severity.

Anti-Neutrophil Cytoplasmic Antibodies Positivity and Anti-Leukotrienes in Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Monocentric Study on 134 Italian Patients.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis associated with asthma, anti-neutrophil cytoplasmic antibodies (ANCA) positivity, and tissue eosinophilia. OBJECTIVE: To describe the presenting clinical features, significant biochemical alterations, and also potential pathogenic factors in adult patients diagnosed in our Center over a period of >20 years. METHOD: A retrospective study of EGPA patients diagnosed from 1994 to 2019 at ASST Grande Ospedale Metropolitano Niguarda Ca' Granda, Milan (Italy), which was performed according to the 1990 American College of Rheumatology criteria and Chapel Hill Consensus Conference definition. A dataset was compiled, registering demographic and clinical features, biochemical analysis at onset, and also the therapies received 3 months prior to EGPA diagnose. Statistical analyses were subsequently conducted dividing patients in 2 groups based on ANCA positivity and comparing them. RESULTS: Two groups were clearly identified by ANCA serology and specific organ involvement in accordance with literature reports; however, our data underline for the first time the association between anti-leukotriene receptor antagonists (LTRAs) and ANCA positivity. The group of previously treated patients presents an OR of 6.42 to be ANCA positive. This finding could be attributed to an imbalanced stimulation of leukotriene receptors, inducing both mast cells activation and an increased neutrophil extracellular traps release from neutrophils. CONCLUSION: Despite the limitations of this retrospective study, the association between LTRAs and ANCA antibodies elucidates the mechanism by which innate immunity is directly involved in tolerance breakdown and autoantibodies production. Validation of our results with targeted studies could clarify the differences between ANCA-positive and ANCA-negative patients with important consequences on the use of some drug classes in the treatment of EGPA and asthmatic subjects.

Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs) induced by anticonvulsants and review of the literature.

BACKGROUND: Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated. CASE PRESENTATION: A total of six patients (2 males and 4 females, age 11-73 years) are described in this study. In all the patients the onset of the severe cutaneous drug reactions was 2-4 weeks after initiating the anticonvulsant therapy: 2 out of 6 patients presented with a drug reaction with eosinophilia and systemic symptoms under therapy with phenytoin; 2 out of 6 presented with Stevens-Johnson syndrome under therapy with lamotrigine; and 2 out of 6 presented with a toxic epidermal necrolysis, one of them under therapy with valproic acid, and the other one under therapy with lamotrigine. Alternative anticonvulsants tolerated after the reaction were: clonazepam, levetiracetam, diazepam, delorazepam and lormetazepam. CONCLUSIONS: In our cases we observed that non aromatic anticonvulsants and benzodiazepines were well tolerated as alternative treatments in six patients with reactions to aromatic anticonvulsivants and that the risk of hypersensitivity reactions to other drug classes was not increased as compared to general population.

Serum tryptase detected during acute coronary syndrome is significantly related to the development of major adverse cardiovascular events after 2 years.

BACKGROUND: One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients. METHODS: We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE). The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed. RESULTS: The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42). The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values. Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001). The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001). CONCLUSION: In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.

Serum tryptase: a new biomarker in patients with acute coronary syndrome?

BACKGROUND: Mast cell tryptase has recently been reported to be involved in atherosclerotic plaque destabilization. However, the results of these reports are conflicting. METHODS: The aim of this study was to characterize the role of tryptase as a prognostic marker of patient cardiovascular complexity in acute coronary syndrome (ACS). Furthermore, its association with an angiographic scoring system [defined by the SYNergy between percutaneous coronary intervention (PCI) with the TAXUS drug-eluting stent and the cardiac surgery (SYNTAX) score] was examined. The serum tryptase was measured at admission in 65 consecutive ACS patients and in 35 healthy controls. In the patients with ACS, a composite measure of clinical and angiographic patient cardiovascular complexity was indicated by two of the following: clinical adverse events at hospitalization, at least 2 epicardial coronary arteries involved in the atherosclerotic disease, more than 1 stent implanted or more than 2 coronary artery disease risk factors. RESULTS: The tryptase measurements were lower in patients without the composite measure (p < 0.0005). Linear regression showed a significant relationship between tryptase levels and the SYNTAX score (SX-score). Conversely, high-sensitivity troponin values did not correlate with either the composite outcome or the SX-score. The predictive accuracy of serum tryptase for the composite outcome was set at the cut-off point of 5.22 ng/ml (sensitivity 81% and specificity 95.7%). CONCLUSION: In ACS patients, serum tryptase levels at admission may predict patient cardiovascular complexity more reliably than currently known biomarkers. Further studies are needed to demonstrate the long-term prognostic role of this biomarker in ACS.

Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics. Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used. Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively). Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.

Unraveling the complexities of drug reaction with eosinophilia and systemic symptoms (DRESS): Insights into clinical, laboratory, and histopathologic features of a case series from an Italian tertiary center.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe and potentially life-threatening drug hypersensitivity reaction. The diagnosis and management of DRESS are complicated due to its heterogeneous clinical and pathologic presentations, delayed onset of signs and symptoms, and unpredictable outcome. This retrospective study aimed to analyze cases of DRESS from a single Italian referring tertiary hospital center (Grande Ospedale Metropolitano Niguarda, Milan, Italy) with a focus on clinical features, causative drugs, histopathologic findings, and treatment. We have included 18 of 32 patients with a probable or definite diagnosis of DRESS. The study observed a slight predominance of women, with antimicrobials and allopurinol identified as the main causative drugs. Clinical manifestations varied, with a monomorphic maculopapular eruption being the most common, whereas facial edema and mucosal involvement were less frequently observed. Multiple organs were commonly affected, with liver and kidney involvement being prominent. Cardiac involvement was associated with the severity of eosinophilia. Laboratory evaluations showed elevated eosinophil levels and increased eosinophil cationic protein levels, supporting the role of eosinophils in DRESS pathogenesis. Histopathologic analysis revealed various patterns often coexisting in the same biopsy in 83% of cases, with interface dermatitis being the most frequent, followed by the perivascular pattern and the spongiotic/eczematous pattern. We observed eosinophils in the biopsy samples in about 50% of patients, and the relationship between peripheral eosinophilia and eosinophils in skin biopsies was not significant. In addition to the RegiSCAR score, age may play a role in predicting disease severity, as older patients with lower scores had poorer outcomes. The prognosis of DRESS depended on early identification, discontinuation of the causative agent, and appropriate therapy. Systemic corticosteroids were the primary treatment option.

Evolution in Endoscopic Sinus Surgery: The Adjuvant Role of Reboot Surgery in Patients with Uncontrolled Nasal Symptoms of Eosinophilic Granulomatosis with Polyangiitis.

PURPOSE: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. METHODS: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. RESULTS: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. CONCLUSIONS: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.

A definite case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) induced by administration of the Pfizer/BioNTech BNT162b2 vaccine for SARS-CoV2.

At the end of December 2020, the anti-SARS-CoV2 vaccination campaign began in Italy. As the number of vaccinated subjects in the general population has increased, several adverse reactions have been observed and reported. Severe cutaneous adverse reactions (SCARs) induced by drugs or vaccines are rare but distinguished by high mortality and include DRESS syndrome or drug induced hypersensitivity syndrome (DiHS), a condition characterized by skin rash, eosinophilia, fever, lymphadenopathy, and involvement of one or more internal organs. Here we present a definite case of DRESS that occured following the administration of Pfizer/BioNTech COVID 19 vaccine. He required hospitalization and was managed with supportive care, antihistamines, and intravenous steroid.

Airborne anaphylaxis: highlighting an invisible enemy.

PURPOSE OF REVIEW: Airborne anaphylaxis is a rare disorder defined by the occurrence of anaphylactic reactions to inhaled allergens, which may arise not only in occupational exposure but also in common settings. Foods are the most common cause of airborne anaphylaxis, even organic mixtures scents. The other important cause is represented by drugs, while in the wide range of other causes, there are often reports on unique cases. This review aims to make an overview about the potential causes of airborne anaphylaxis, by analysing what is described in literature on this topic. RECENT FINDINGS: Concerning epidemiology, no data on specific prevalence of airborne allergy in adults are available. To date, only one study evaluated the specific prevalence of airborne allergy with anaphylaxis to foods in children, resulting in 5.9% of reactions due to exposure to aerosolized foods, compared with 78% of reactions caused by food ingestion. In addition to anaphylaxis, airborne-related reactions may also present with symptoms such as rhino-conjunctivitis, wheezing, dyspnoea and asthma. SUMMARY: A detailed anamnesis facilitates a correct diagnosis, which allows appropriate therapeutic and preventive interventions, but, similarly to rare diseases in general, only specialized doctors are able to implement it. The assumption of the approach used in emergency medicine for other causes of anaphylaxis, that is referring the patient at discharge to an allergist who will teach the basic notions to recognize symptoms and access the appropriate therapy, would allow the patient to avoid situations of serious danger.

Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm3: A Post Hoc Analysis from the ANANKE Study.

Purpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300-450 cells/mm3 subset of patients. Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300-450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected. Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300-450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300-450 subset showed similar reductions in AER (-94.8% vs -92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered. Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300-450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300-450 patients as in the total population.

Omalizumab Use in Chronic Spontaneous Urticaria during Pregnancy and a Four Years' Follow-Up: A Case Report.

Chronic spontaneous urticaria (CSU) is a benign skin disorder usually responsive to treatment; however, at times it can be difficult to control and become very debilitating. We discuss the case of a woman with CSU that was unresponsive to H1-antihistamines who was treated with omalizumab and became pregnant during omalizumab treatment. We also considered the follow-up of the mother and newborn for 4 years after delivery. Our case report confirms that omalizumab is a safe and effective therapeutic option, after careful evaluations in terms of cost-effectiveness, in pregnant and lactating women with severe chronic urticaria. Assessment throughout follow-up confirmed a regular progression of pregnancy parameters and no adverse reaction was documented in the child from birth to 4 years of age.