Rapid drug desensitization to taxanes: a descriptive study from Turkey.

AIM: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD). METHODS: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards. RESULTS: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male. CONCLUSION: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Successful desensitization under antihistamine suppression in a case with urticaria due to osimertinib.

INTRODUCTION: Osimertinib is an approved therapy for patients with a Thr790met (T790M) mutation diagnosed with non-small cell lung cancer (NSCLC) that progresses during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. However, in 7-13% of patients, drug-related side effects lead to discontinuation of osimertinib treatment. In such cases, osimertinib desensitization is a treatment option that can be considered. CASE REPORT: A 59-year-old female patient, who was followed up with the diagnosis of stage 4 NSCLC, was consulted to the allergy clinic because of urticaria. The patient developed urticaria plaques 20 h after the third dose of osimertinib tablet. MANAGEMENT & OUTCOME: With the diagnosis of osimertinib-induced urticaria, desensitization was planned for the patient. Treatment was started with a dose of 0.1 mg/day osimertinib. The procedure was completed in approximately 50 days, and a dose of 80 mg/day was reached with antihistamine suppression. DISCUSSION: Here, a successful osimertinib desensitization in a patient with a history of osimertinib-related type 1 allergic reaction is reported. Osimertinib desensitization is a treatment option that should be considered in cases where treatment has to be ceased due to drug-related side effects.

The adequacy of current diagnostic criteria for making a diagnosis of ABPA.

Introduction: Currently, there are four different diagnostic criteria systems for allergic bronchopulmonary aspergillosis (ABPA): The Rosenberg-Patterson, Seropositive ABPA (ABPA-S), Central Bronchiectasis and ABPA (ABPA-CB), and the International Society for Human and Animal Mycology (ISHAM) ABPA study group criteria. This study aims to retrospectively compare these four diagnostic criteria in ABPA patients. Materials and Methods: Patients who were followed up with the diagnosis of ABPA were retrospectively re-evaluated using these four diagnostic criteria, and the superiority of these criteria to each other was determined. Result: A total of 10 ABPA patients were included in the study. Seven patients were diagnosed according to ISHAM ABPA study group diagnostic criteria and six patients according to the Rosenberg-Patterson diagnostic criteria. None of the patients fulfilled the criteria when evaluated individually with ABPA-S and ABPA-CB. Of patients diagnosed by ISHAM, five had a total IgE level above 1000 IU/mL and two had below 1000 IU/mL. Conclusions: We demonstrated that the diagnostic criteria developed by the ISHAM ABPA study group were superior to the others in diagnosing ABPA in cases with a total IgE level above 1000 IU/mL. However, all these criteria seem to be sufficient to diagnose ABPA in patients with a total IgE below 1000 IU/mL. We believe the necessity to demonstrate presence of Aspergillus fumigatus precipitating antibodies or specific IgG positivity should be questioned particularly in patients with radiologic findings compatible with ABPA and a total IgE level below 1000 IU/mL.

Effectiveness of as-needed antihistamines in chronic spontaneous urticaria patients under omalizumab treatment.

The question how second-generation antihistamines (sgAHs) should be used when chronic spontaneous urticaria (CSU) is under control with omalizumab is still unanswered. This study aimed to investigate the effectiveness of as-needed sgAHs in patients with well-controlled urticaria under omalizumab treatment. Patients from four different urticaria centers who were treated with omalizumab 300 mg/4 weeks for at least 3 months, had well-controlled urticaria (Urticaria Control Test: 16 > UCT≥12) and were using sgAHs only if needed, were included in this study. In order to assess effectiveness of sgAHs, change in the itch, hives, and total itch-hives scores before and after sgAHs were evaluated using modified urticaria activity score-twice daily. Fifty-three patients [38 female (71.7%)] with mean age 41.1 ± 11.4 years were included in this study. Median sgAH intake per patient throughout the 4 week-intervals was 3 (2-5) tablets. sgAH intake decreased itch, hives and total itch-hives scores 45.7% ± 52.9, 42.4% ± 39.1, and 50.2% ± 51.1, respectively (P < .001 for all). This decrease was similar in both isolated-urticaria and urticaria-and-angioedema phenotypes. Baseline IgE levels were positively correlated with the decrease of three symptom scores (r = 0.31, P = .05; r = 0.375, P = .017; r = 0.31, P = .05, respectively) that showed in patients with higher baseline total IgE levels, as needed sgAH intake decreased the symptom scores less. Our study showed that sgAHs may still be an effective option for the treatment of the intermittent symptoms in patients with well-controlled urticaria under omalizumab treatment. Baseline total IgE levels may be used as a potential biomarker for sgAH effectiveness in these patients.

Effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, steroid dependence, and small airways in patients with severe eosinophilic asthma

Background/aim: The efficacy of mepolizumab has been largely demonstrated in clinical trials in patients with severe eosinophilic asthma (SEA). However, reports on experience with mepolizumab in a real-life cohort are limited. Moreover, data about the effectiveness of mepolizumab on small airways is scarce. This study evaluated the effectiveness of mepolizumab therapy on symptoms, asthma exacerbations, blood eosinophils, steroid dependence, and small airways in a real-life cohort of patients with SEA. Materials and methods: We retrospectively analyzed patients with SEA who were receiving fixed-dose mepolizumab. The effects of mepolizumab on clinical, laboratory, functional parameters were evaluated at 12th, 24th, and 52nd weeks. Small airways were assessed with the FEF 25-75. Results: A total of 41 patients were enrolled in the study. Mepolizumab significantly reduced asthma exacerbation rates, reduced mOCS dose, and improved asthma control test (ACT) scores at 12th, 24th, and 52nd weeks. However, we found no significant changes in FEV1 and FEF25-75 values at baseline, 12th, 24th, and 52nd weeks (78.9 ± 23.3%, 82.9 ± 23.4%, 81.9 ± 23.9%, and 78.9 ± 23.5% for FEV1; 45.1 ± 23.1%, 48.8 ± 23.5%, 48.7 ± 23.1%, and 41.0 ± 20.1% for FEF25-75, respectively) Conclusion: In this study, mepolizumab significantly improved all outcomes (symptom scores, asthma exacerbations, OCS sparing, and blood eosinophils) except functional parameters. Still, despite the dose reduction in mOCS dosage, no significant deterioration was observed in FEV1 and FEF25-75 values.

Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study

Background/aim: Oral corticosteroid (OCS)-dependent severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps (SEA-CRSwNP) would be a suitable phenotype for mepolizumab treatment. This study evaluated the short-term efficacy of mepolizumab treatment in OCS-dependent SEA-CRSwNP. Materials and methods: Baseline and 24th week results [daily OCS doses, asthma exacerbation frequency, asthma control test (ACT) scores, blood eosinophil levels, FEV1 values, and numerical analog scale (NAS) of CRSwNP symptoms] of patients who were treated for at least 24 weeks with mepolizumab were retrospectively evaluated and compared. Results: A total of 16 patients were enrolled in the study. Mepolizumab was discontinued in one patient due to side effects. The daily OCS dosage was reduced from baseline in all patients, and at week 24 OCS was discontinued in 40% of the patients (baseline mean steroid dose: 9.2 ± 5.2 mg, 24th week: 1.3 ± 1.4 mg; P < 0.001). The number of asthma exacerbations within 24 weeks significantly decreased after beginning mepolizumab treatment (2.1 ± 2.7 vs. 0.07 ± 0.26; P = 0.012), and a significant increase in ACT scores (baseline mean ACT: 18 ± 5.7; 24th week mean ACT: 23.3 ± 3; P = 0.006) was observed despite the decrease in daily OCS dosages. There was no significant difference in FEV1 values between baseline and week 24. Evaluation of the general symptoms of CRSwNP, as per NAS, revealed that the baseline mean NAS was 5.6 ± 4.4, and the 24th week mean NAS was 3.2 ± 3.2 (P = 0.021). Conclusion: This is the first real-life study evaluating the short-term efficacy of mepolizumab treatment on OCS-dependent SEA-CRSwNP. This study demonstrates that mepolizumab is an effective and safe biologic for the treatment of this severe asthma subphenotype.

Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

Introduction: The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. Materials and Methods: A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Result: Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. Conclusions: The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.