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Introduction: We aimed to investigate the frequency and sociodemographic and clinical distinguishing features of asthmatic patients in whom long-acting muscarinic antagonists (LAMA) were added to maintenance therapy in our clinic., Methods: In this cross-sectional study, data on sociodemographic, phenotypic, and clinical characteristics of patients with asthma using Steps 4 and 5 medications, who were followed up in our center for at least 1 year, were obtained from file records. Whether the patients received add-on LAMA for at least 6 months was also noted., Results: A total of 279 patients with asthma using Steps 4 and 5 medications (female/male: 215/64) with a mean age of 50.84 ± 12.42 years were included in the study. Seventy-nine (28.3%) patients (female/male: 60/19) with a mean age of 52.45 ± 11.61 years used LAMA as an add-on treatment; 28 (37.8%) at Step 4 and 51 (24.8%) at Step 5. In Steps 4 and 5, there was no difference in terms of age, sex, body mass index, smoking status, being allergic or eosinophilic, phenotype, and asthma onset between patients with and without add-on LAMA. Asthma control in the previous year was better, and minimum forced expiratory volume in 1s (FEV1) was lower in patients with LAMA than in those without in Step 4 (P = 0.001 and P = 0.030, respectively). In Step 5, the rate of being well-controlled was higher in those without add-on LAMA (P < 0.001). The number of exacerbations in the previous year was higher, and minimum and maximum FEV1 were lower in patients with add-on LAMA (P < 0.001 and P < 0.001, respectively)., Conclusion: Our study showed that add-on LAMA treatment was effective in increasing asthma control in patients using Step 4 medication independent of baseline characteristics and asthma phenotype., Competing Interests: The authors have no conflicts of interest to declare.

Introduction: The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies., Methods: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation., Primary Endpoint: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores)., Results: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation., Conclusion: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article., (© 2024. The Author(s).)

Background: Following the increased use of biological agents, a subset of patients experiences hypersensitivity reaction (HSR). We reported our experience with rapid drug desensitization (RDD) to nine biologics (rituximab, infliximab, cetuximab, trastuzumab, pertuzumab, nivolumab, brentuximab, tocilizumab and filgrastim) and identified risk factors for breakthrough reactions (BTRs)., Method: This was a retrospective review (2013-2022) of patients with immediate HSRs to biological agents. Initial HSRs were classified as grade 1, 2, or 3 in their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed using implicated agents. The phenotypes of HSRs were defined as Type I, cytokine-release syndrome (CRS), mixed reactions (cytokine-release + type I) based on history, clinical presentations and skin tests with implicated biologicals. A 12-step RDD protocol was used., Results: The study comprised 45 patients (F/M: 31/14, median age: 55 (range: 20-69)). Majority of the patients reacted at the first infusion (n: 29/45, 64.4%). The majority of initial HSRs were grade 3 (n: 24/45, 53.3%) and grade 2 (n: 21/45, 46.6%); none were grade 1. Initial reactions were presented as type I (n: 20/45, 44.4%), CRS (n: 12/45, 26.6%) and mixed (n: 13/45, 28.8%). A total of 258 RDDs were performed and 98.4% of them were completed successfully. BTRs occurred in 36/258 (13.9%) infusions of RDDs. There was no significant association between the BTRs and age, drug cycle, SPT and IDT positivity, gender, comorbidities, or atopy., Conclusion: In our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Objective: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes., Methods: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response., Results: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16)., Conclusion: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Taxanes can cause hypersensitivity reactions (HSRs), which pose a significant challenge in the treatment of malignancies. Patients who are eligible for rapid drug desensitization (RDD) can continue treatment; however, some patients experience breakthrough reactions (BTRs). Data about risk factors for BTRs during RDDs in patients with HSRs to taxanes are limited., Methods: This was a multicenter, retrospective study of patients with immediate-HSRs to taxanes. Initial HSRs were classified as grade 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated taxanes. A 12-step protocol was used during RDD., Results: The study comprised 75 patients (F/M: 63/12, mean age 49.92 ± 11.72 years, 43 HSRs to paclitaxel, 32 HSRs to docetaxel). The majority of reactions (86.7%) occurred during the first or second exposure. The prevalence of drug allergy history was higher in patients with paclitaxel HSR than in those with docetaxel HSR, although it was not statistically significant (23.3% vs. 6.3%). The initial HSRs were mostly grade 2 (n = 50, 66.7%) or grade 3 (n = 22, 29.3%). Skin tests with implicated taxanes were done on 48 patients, and the rate of positive response in patients with grade 1, 2, and 3 initial HSRs were 50%, 17.6%, and 16.7%, respectively. . A total of 255 RDDs were completely performed, although BTRs occurred in 27 (grade 1, 55.6%; grade 2, 40.7%; grade 3, 3.7%). There were no statistically significant correlations between the risk of BTR and age, drug cycle, gender, positivity of skin test or atopy. The step reduction was successfully done on 9 eligible patients with mild or moderate HSRs during the 12-step RDDs., Conclusions: Our experience demonstrates a 100% success rate in completing the 255 RDDs for taxanes, affirming the safety and efficacy of the RDD within the study population., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Summary: Background. Allergic bronchopulmonary aspergillosis (ABPA) is an endotype of severe asthma which frequently needs biologics for their steroid sparing effect. We aimed to evaluate the outcomes of reducing the omalizumab dose in patients with ABPA who were on long-term omalizumab treatment. Methods. Once asthma was controlled, two approaches were used to reduce total monthly omalizumab dose: 1) both extending dose intervals from 2 to 4 weeks and decrease omalizumab dose, 2) to reduce omalizumab dose while keeping dose intervals stable. Results. Thirteen patients with ABPA (8F/5M, mean age 53.4 ± 13.0 years) were included. Pre-omalizumab, mean numbers of attacks and hospitalizations were 2.5 ± 1.5 and 1.3 ± 0.8, mean oral corticosteroid (OCS, as methylprednisolone) dose was 12.2 ± 10.4 mg daily. First omalizumab dose reduction was made to all patients at a median time of 35 months (min 13, max 47). The 2 nd dose reduction was made in four patients at median of 23.5 months. Mean OCS decreased to 0.69 ± 0.95 mg/day (p = 0.001) in the 1st year of omalizumab, could be stopped in 11 patients in last evaluation. Attacks/hospitalizations decreased significantly to 0.31 ± 0.86 and 0, respectively, in the 1st year of omalizumab. Total omalizumab dose was reduced by median 40% (min 20, max 60) in 1st intervention and 50% (min 20, max 67) after 2nd intervention. After omalizumab dose reduction, asthma control did not deteriorate and there was no need to increase the omalizumab or OCS-dose. Conclusions. Decreasing the total omalizumab dose does not cause clinical deterioration in ABPA after the disease is controlled.

Introduction: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC)., Patients and Methods: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria., Results: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC., Conclusions: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer., Competing Interests: Conflicts of interest and sources of funding: B.E. is supported by the European Urological Scholarship Programme through a 1-year research scholarship., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction of inhaled corticosteroids (ICS) has been the cornerstone of the long-term management of asthma. ICSs either alone or in combination with long-acting beta-2 agonists have been shown to be associated with favorable asthma outcomes. However, asthma control is still reported to be below expectations all around the world. Research in the last decades focusing on the use of ICS/formoterol both as maintenance and as needed (maintenance and reliever therapy approach) showed improved asthma outcomes. As a result of recent developments, Turkish Asthma Guidelines group aimed to revise asthma treatment recommendations. In general, we recommend physicians to consider the risk factors for poor asthma outcomes, patients' compliance and expectations and then to determine "a personalized treatment plan." Importantly, the use of short-acting beta-2 agonists alone as a symptom reliever in asthma patients not using regular ICS is no longer recommended. In stepwise treatment approach, we primarily recommend to use ICS-based controllers and initiate ICS as soon as possible. We define 2 different treatment tracks in stepwise approaches as maintenance and reliever therapy or fixed-dose therapy and equally recommend each track depending on the patient's risks as well as decision of physicians in a personalized manner. For both tracks, a strong recommendation was made in favor of using add-on treatments before initiating phenotype-specific treatment in step 5. A strong recommendation was also made in favor of using biologic agents and/or aspirin treatment after desensitization in severe asthma when indicated.

Background: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting., Methods: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines., Results: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs., Conclusions: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Background: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT., Objective: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk., Methods: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings., Results: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT., Conclusions: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Context: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has superior accuracy for detection of metastatic lesions in patients with prostate cancer (PC). Although PSMA PET has a prominent role in primary and secondary imaging of PC, data on its role in assessing treatment response in advanced PC are limited., Objective: To review current data in the literature regarding the impact of antiandrogen therapy on PSMA expression of metastatic sites and the role of serial (baseline and at least 1 follow-up scan) PSMA PET to assess treatment response in patients with metastatic PC., Evidence Acquisition: A comprehensive literature search in the PubMed database was performed using the terms "PSMA expression prostate", "PSMA regulation", "PSMA PET response assessment", and "serial PSMA PET"., Evidence Synthesis: Serial PSMA PET studies (baseline and at least 1 follow-up scan) provide valuable data regarding PSMA expression changes after systemic treatment in patients with metastatic PC. PSMA PET-detected flare and upregulation of PSMA expression following hormonal intervention seem to be early events resolving after 3 mo of treatment. PSMA PET imaging is essential in selecting patients for 177 Lu-PSMA radioligand therapy (RLT). Growing evidence favors its use in assessing treatment responses after RLT. Preliminary evidence indicates the value of PSMA PET for assessment of the treatment response in patients receiving systemic treatment other than RLT for metastatic PC., Conclusions: PSMA flare following antiandrogen therapy seems to be an early event and thus PET scans should be performed no earlier than 3 mo after the start of treatment. PSMA PET has a promising role in tailoring treatment according to the specific needs of individual patients and assessing responses following systemic treatment in patients with advanced PC., Patient Summary: This review describes how a sensitive imaging method can be used to assess the tumor response to treatment for metastatic prostate cancer., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: In patients with severe asthma, individualized treatment, and appropriate phenotyping are required to achieve control. In our study, our aim was to examine the characteristics of a specific patient group in a specialized tertiary asthma outpatient clinic, which is the primary setting for evaluating severe asthma patients, with the intention of obtaining national data., Materials and Methods: In this cross-sectional observational study, sociodemographic, clinical presentations, laboratory results, and spirometry measurements of patients with severe asthma who were followed up in our specialized asthma outpatient clinic for at least one year were recorded. Patients were defined as eosinophilic if they had a blood eosinophil count of 300/µL or higher at least twice during the oral corticosteroid free-period or 150/µL or higher under oral corticosteroids as allergic if they had sensitization to at least one inhalant allergen consistent with their history., Result: Overall, 201 severe asthma patients (74.1% female) with a median disease duration of 15 (min-max= 1-49) years and a median follow-up duration of 7 (min-max= 1-40) years were analyzed. Most of the patients (56.7%) had adult-onset asthma [median age of onset was 32 (min-max= 10-62) years]. Overweight and obese patients were in the majority (31.8%, and 41.8%, respectively) and the median body mass index was 29 (min-max= 17.5-49.5). More than half of the patients (55.2%) had controlled asthma and the median Asthma Control Test score at the last visit was 23. Biologic therapies were applied to 73.1% (n= 147) of the patients [60.5% (n= 89) omalizumab, 39.5% (n= 58) mepolizumab]. Half of the group was allergic (49.3%) and three-quarters of them were eosinophilic (72.1%). Allergic patients had earlier asthma onset and had more controlled disease than nonallergic ones. Eosinophilic patients were younger and less obese than noneosinophilic patients. Obese and late-onset asthmatics had more uncontrolled disease than normal weight subjects and early onset patients., Conclusions: The high rate of disease control in the patients with severe asthma in the current study demonstrated the importance of targeted individualized therapy with accurate phenotyping in specialized asthma outpatient clinics.

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

Background: Anaphylaxis is a very dynamic issue with its incidence and trigger profile changing over the years. We aimed to compile the characteristics of anaphylaxis cases diagnosed in our clinic prospectively and to make a comparison between diagnostic criteria proposed by National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) and World Allergy Organization (WAO)., Method: Three-item diagnostic criteria recommended by NIAID/FAAN (2006) were used in the diagnosis of anaphylaxis. The clinical features of the cases, risk factors, etiologies, severity of anaphylaxis, and treatment approach were determined. The same patients were also classified by current WAO diagnostic criteria., Results: A total of 204 patients (158F/46 M, median age 45.3 years) were included. Drugs (65.2%), venom (9.8%) and food allergies (9.3%) were the top 3 etiologies. Among drug triggers, chemotherapeutics were the most common (17.7%), followed by antibiotics (15.3%) and non-steroidal anti-inflammatory drugs (14.2%). The patients were mostly diagnosed with the second criterion (84.8%), followed by the first criterion (11.8%) and the third criterion (3.4%) of the NIAID/FAAN criteria. In terms of WAO criteria, 82.8% of the patients were diagnosed with the first criterion, and 14.3% with the second criterion while 2.9% of the patients did not meet the WAO criteria. The severity of anaphylaxis was evaluated as grade-2, 3 and 4 in 30.9%, 64.2%, and 4.9% of the patients, respectively. Adrenaline was administered to 31.9% of the patients especially who had angioedema and bronchospasm (p = 0.04)., Conclusion: Our data suggest that covering more details in patient's history may prevent possible underdiagnosis and WAO diagnostic criteria seem to be insufficient in some patients. We believe that our results will contribute to the literature on anaphylaxis and would be groundwork for future studies., (© 2023 The Authors.)

Aims: To evaluate the cost-effectiveness of standard-of-care treatment (SoC) to SoC in combination with omalizumab (OML + Soc) in patients with severe asthma using real-world prospective clinical data from four major medical centers in Turkey., Materials and Methods: Between February 2018 and November 2019, a total of 206 patients with severe asthma, including 126 of whom were in the OML + SoC group and 80 in the SoC group, were followed for 12 months to evaluate their asthma status and quality of life. Cost data for this patient-level economic evaluation were sourced from the MEDULA database of the hospitals and expressed in Turkish Lira (₺). Efficacy data were obtained by means of Turkish versions of the Asthma Control Test for asthma status, the 5-level EQ-5D-5L version (EQ-5D-5L), and the Asthma Quality of Life Scale for quality of life. A Markov model with 2-week cycles was specified, comparing costs and treatment effects of SoC vs. OML + SoC over a lifetime from the Turkish payer perspective., Results: Per-patient costs were ₺23,607.08 in the SoC arm and ₺425,329.81 in the OML + Soc arm, for a difference of ₺401,722.74. Life years (LY) and quality-adjusted life years (QALY) were 13.60 and 10.08, respectively, in the SoC group; and 21.26 and 13.35, respectively, in the OML + SoC group, for differences of 7.66 LYs and 3.27 QALYs. This yielded an incremental cost-effectiveness ratio of an additional ₺52,427.04 to gain 1 LY and an incremental cost-utility ratio of an incremental ₺122,675.57 to gain 1 QALY; the latter being below the ₺156,948 willingness-to-pay threshold for Turkey referenced by WHO. One-way and multivariate sensitivity analyses confirmed the base-case results., Conclusion: Whereas most economic evaluations are based on aggregate data, this independent cost-effectiveness analysis using prospective real-world patient-level data suggests that omalizumab in combination with standard of care is cost-effective for severe asthma from the Turkish public payer perspective.

Background: CoronaVac, the first coronavirus disease 2019 vaccine administered in our country, was found safe in clinical trials., Objective: We aimed to reveal the rate and features of CoronaVac vaccine-associated allergic reactions among vaccinated healthcare workers (HCWs) in real-life., Methods: This study was planned as a questionnaire-based study. Participants who reported a postvaccination allergic reaction were interviewed on phone and their medical records were also checked for confirmation., Results: A total of 2,488 HCWs took part in the study and 4,054 postvaccination complete questionnaire-responses were obtained. Twenty-one HCWs (female: male, 17:4) with a mean age of 40.95 ± 10.09 stated that they had an allergic reaction after a total of 23 vaccine injections. Accordingly, the reaction rate was 0.56% among all vaccine doses. The most common reactions were systemic skin reactions (2.7%) consisting of generalized pruritus, diffuse pruritic erythema, urticaria, and maculopapular rash. That was followed by local injection site reaction (0.12%). Anaphylaxis was reported in 4 cases (0.09%) with a mean onset time of 12 ± 6 minutes. One of them had a history of anaphylaxis with 2 drugs, another had venom and food allergy. Three of the subjects had level 2 diagnostic certainty according to the Brighton Collaboration criteria and one had level 3. All anaphylaxis cases were discharged within 24 hours and none of them required intensive care., Conclusion: Our study demonstrated that allergic reactions to CoronaVac were rare and mostly mild. Although anaphylaxis was also rare, the importance of early intervention with close follow-up was once again emphasized., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Introduction: To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents., Materials and Methods: A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease., Result: Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%)., Conclusions: The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Background: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized., Method: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed., Results: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable., Conclusions: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Allergen-specific immunotherapy (AIT) is accepted as the only disease-modifying therapy for IgE-mediated allergic airway diseases and hymenoptera venom allergy. AIT requires repeated contact between patient and physician or nurse in the hospital. Because it is a long-term treatment, compliance is essential issue to obtain maximal efficacy. Coronavirus disease 2019 (COVID-19) pandemic reshaped doctor-patient interaction and pattern of hospital admissions., Objective: We aimed to determine the possible changes in the administration of AIT and associated factors, in addition to the characteristics of patients diagnosed with COVID-19 infection., Methods: Adult patients who underwent AIT for hymenoptera venom allergy, allergic rhinitis or allergic asthma between 11 March 2020 and 31 January 2021 were included in our retrospective study. Perennial and preseasonal AIT practices were evaluated. We identified patients with COVID-19 infection among the ones who received AIT., Results: The mean age of 215 patients was 37.8±11.9 years and 52.1% of the patients were female. In our study, 35.4% of perennial AIT patients did not continue treatment after the COVID-19 pandemic, and the cause was patient-related in 66.7% of the cases. Compliance was 70.7% in patients receiving perennial AIT. The highest compliance rate for AIT was for venom allergy (86.5%). Thirty-four patients (15.8%) were diagnosed with COVID-19 infection. No mortality due to COVID-19 infection was observed in those who underwent AIT., Conclusion: COVID-19 pandemic has reduced compliance to AIT. Compliance was higher in venom immunotherapy than in aeroallergens. Severe COVID-19 infection and COVID-19 related death were not observed in patients receiving AIT., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response., Methods: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month., Results: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/μL to 89/μL and 85/μL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations., Conclusion: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings., (© 2021 S. Karger AG, Basel.)

Introduction: Data showing effectiveness of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are limited., Methods: This is a single-center retrospective chart review of patients with EGPA treated with mepolizumab. Clinical, laboratory, functional parameters and asthma, rhinitis control, and quality of life scores (Asthma Control Test [ACT], Asthma Quality of Life Questionnaire [AQLQ], Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ], and SinoNasal Outcome Test [SNOT]-22) were evaluated at the baseline, 6th month, and 12th month. Complete response was defined as the absence of asthma and/or ear, nasal symptoms and exacerbations with a prednisone of ≤7.5 mg/day, partial response if it was achieved with a prednisone of >7.5 mg/day., Results: Overall, 25 patients (18 F/7 M) with a median age of 47 years (23-76) were enrolled. Mepolizumab 100 mg/month was administered (dose increased to 300 mg/month in 3 patients). Mepolizumab significantly decreased daily dose of oral corticosteroid (OCS) from 11.04 mg to 3.65 mg together with a significant improvement in ACT, AQLQ, RQLQ, and SNOT-22 scores and a significant reduction in asthma exacerbations and blood eosinophil count at the 6th and 12th month (all p values <0.05). The mean forced expiratory volume in 1 s increased (at baseline: 1.88 L to 2.46 L at the 12th month [p = 0.037]). Seventy-six percent of patients responded completely at the 6th month and 81.25% at the 12th month. The complete responders at the 6th and 12th month were older than partial responders and nonresponders (p = 0.030 and p = 0.057, respectively). Patients with complete response at the 6th month were on lower doses of OCS than partial responders and nonresponders (p = 0.029)., Conclusions: Low-dose mepolizumab was effective in EGPA patients by improving sinonasal and asthma outcomes, while reducing the need for OCS., (© 2022 S. Karger AG, Basel.)

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: All platin-based chemotherapeutics can cause hypersensitivity reactions (HSRs). With rapid drug desensitization (RDD), few patients experience breakthrough reactions (BTR) during desensitization. However, data about risk factors for BTRs during RDD in patients with HSRs to platins are limited. We first aimed to describe characteristics of our platin-reactive population and to validate the Brigham and Women's Hospital's (BWH's) RDD protocol in our population along with their outcomes with RDD. Our second aim was to identify the risk factors for BTRs., Method: This was a retrospective chart review (2013-2020) of patients with symptoms of immediate HSRs to platins. Initial HSRs were classified as grade 1, 2, or 3 based on their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed with implicated platins. A 12-step protocol was used during RDD., Results: The study comprised 65 women and seven men (mean age 57.78 ± 8.73 years). Initial HSRs to carboplatin, cisplatin, and oxaliplatin occurred in 38, 13, and 21 patients, respectively. All patients reacted at the fifth (median) recurrent infusions (min:1, max:20). The median values for carboplatin, cisplatin, and oxaliplatin were 6 (1-20), 3 (1-15), and 3 (1-11), respectively. Most initial HSRs were grade 2 (n = 40, 55.6%) and 3 (n = 27, 37.5%); only 6.9% (n = 5) were grade 1. Patients with grade 1, 2, and 3 initial HSRs had positive platin skin test results at rates of 80%, 74%, and 88%, respectively.A total of 232 RDDs were performed in 72 patients and 98.7% of these desensitizations were completed. BTRs occurred in 56 (24.1%) (grade 1 n = 14, 25%; grade 2 n = 32, 57%; grade 3 n = 10, 18%) of these desensitizations. Breakthrough reactions were more severe in patients with positive SPTs or 1:100 or 1:10 dilutions of IDT (p = 0.014). BTR was not observed during RDD in any of the patients with positive 1:1 dilutions of IDT. Positivity on prick or 1:100 or 1:10 IDT increased the risk of BTR 5.058 times. There was no significant association between the risk of BTRs and age, drug cycle, sex, comorbidities, or atopy., Conclusion: In our experience, 98.7% of 232 RDDs to platins were completed successfully, showing that RDD was safe and effective. Drug skin test positivity is a potential marker for identifying high-risk patients who will have BTRs during RDDs to platins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2021 Published by Elsevier Inc. on behalf of World Allergy Organization.)