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The Journal of Allergy and Clinical... Jan 2024There has been a paradigm shift in the management of aspirin-exacerbated respiratory disease (AERD). It started in 2015 when the first biologic was Food and Drug... (Review)
Review
There has been a paradigm shift in the management of aspirin-exacerbated respiratory disease (AERD). It started in 2015 when the first biologic was Food and Drug Administration (FDA) approved for severe eosinophilic asthma. Thus, there emerged a new era in the treatment of patients with type 2-mediated airway diseases. This has led to an increasing number of options for patients, undoubtably a great thing, but has left clinicians without a clear answer for how to balance the therapies that exist for AERD, what to recommend for treatment, and how to best assess the benefits and risks of each therapy. This paper aims to explore these benefits and risks, and to provide a roadmap for future studies.
Topics: Humans; Aspirin; Asthma, Aspirin-Induced; Respiration Disorders; Desensitization, Immunologic; Sinusitis; Asthma; Biological Products; Nasal Polyps; Chronic Disease; Rhinitis
PubMed: 37778627
DOI: 10.1016/j.jaip.2023.09.019 -
The Journal of Allergy and Clinical... Aug 2023Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab.
OBJECTIVE
We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU.
METHODS
PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis.
RESULTS
Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings.
CONCLUSIONS
This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Immunoglobulin E; Treatment Outcome; Chronic Urticaria; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37263348
DOI: 10.1016/j.jaip.2023.05.033 -
Dermatology Practical & Conceptual Oct 2023Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU).
INTRODUCTION
Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU).
OBJECTIVES
To investigate Th1, Th2, and Th17 cytokine profiles in CSU and to evaluate the possible effect of omalizumab treatment.
METHODS
Patients who were followed up for CSU, as well as healthy volunteers, were included in the study. To assess urticaria activity, the 7-day-Urticaria Activity Score (UAS-7), the Urticaria Control Test (UCT), and the Chronic Urticaria Quality of Life Questionnaire (CU-QoL) were filled. Serum levels of IL-6, IL-17, IL-31, eotaxin, RANTES, TNF-α, and TSLP were analyzed by ELISA and compared in CSU and control groups. The patients were analyzed in two groups as the omalizumab group and the non-omalizumab group based on their treatment status.
RESULTS
Total IgE, ESR, CRP, RANTES, and TNF-a were significantly different in the overall comparison of the three groups: CSU-receiving omalizumab, CSU-not receiving omalizumab, and control groups (P <0.01, 0.015, <0.01, <0.01 and <0.01 respectively). Total IgE, CRP, RANTES, and TNF-α values were similar in those who received and did not receive omalizumab, yet these biomarkers were significantly higher in both groups than in the control group (P < 0.05). Statistical significance in ESR was observed only between the CSU-receiving omalizumab group and the control group (P = 0.01). Within the CSU patients, there was a slight but significant correlation between UCT and TNF-α (P = 0.008, r = 0.32) and IL-17 (P = 0.06, r = 0.33) levels.
CONCLUSIONS
The investigated cytokine profile in CSU patients may differ from healthy controls, particularly with the higher levels of RANTES and TNF-α, and omalizumab treatment does not seem to affect that profile in CSU patients.
PubMed: 37992372
DOI: 10.5826/dpc.1304a272 -
BMC Pulmonary Medicine Oct 2023Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been...
BACKGROUND
Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA.
METHODS
This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab.
RESULTS
Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p < 0.05, p < 0.01, and p < 0.01, respectively). After the initiation of omalizumab administration, the median corticosteroid dose, acute exacerbation rate, hospitalization rate, and mean blood eosinophil count decreased when compared with the baseline values (p < 0.05, p < 0.05, p < 0.01, and p < 0.05, respectively). A reduction in the total serum IgE level was observed in patients with ABPA without AR compared with that in patients with AR (p < 0.05). One patient reported a concurrent skin rash, which spontaneously resolved without medication.
CONCLUSION
It is safe and effective to prescribe omalizumab to patients with ABPA, irrespective of whether they have AR. Dose adjustment of omalizumab is safe after disease control. The total serum IgE level might be a predictor of the effectiveness of omalizumab in patients without AR.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Aspergillosis, Allergic Bronchopulmonary; Retrospective Studies; Adrenal Cortex Hormones; Rhinitis, Allergic; Immunoglobulin E
PubMed: 37833657
DOI: 10.1186/s12890-023-02696-x -
Clinical and Experimental Dermatology Mar 2024Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are...
BACKGROUND
Managing a pregnant patient with chronic spontaneous urticaria (CSU) is often challenging. Recent data have shown that most CSU treatments in pregnant patients are second-generation H1 antihistamines (sgAHs), while data on the safety of omalizumab are scant.
OBJECTIVES
To evaluate, in a routine clinical practice setting, the efficacy and safety of omalizumab in patients with severe CSU refractory to sgAHs who either became pregnant during treatment or who started the drug during pregnancy.
METHODS
We conducted a retrospective study of women aged ≥ 18 years who were pregnant, who received one or more doses of omalizumab at any time during their pregnancy or who were taking omalizumab at the time of, or in the 8 weeks before, conception.
RESULTS
Twenty-nine pregnant patients were evaluated: 23 (79%) conceived a child while taking omalizumab (group A), while 6 (21%) started omalizumab treatment during pregnancy (group B). Among patients in group A, we observed 23 births (21 liveborn singletons and 1 liveborn twin pair) and 1 miscarriage. Fifteen (65%) patients discontinued omalizumab after confirming their pregnancy, while eight (35%) were exposed to omalizumab during their entire pregnancy. In group B, omalizumab was introduced at a mean (SD) 10.83 (3.60) weeks' gestation and all patients were exposed to it until the end of pregnancy. In this group, there were seven liveborn infants (five singletons and one twin pair). No adverse events, pregnancy complications or congenital anomalies in newborns were recorded in either group.
CONCLUSIONS
Omalizumab for CSU treatment before and during pregnancy does not appear to have negative effects on maternal or fetal outcomes.
Topics: Adolescent; Adult; Female; Humans; Infant, Newborn; Pregnancy; Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Omalizumab; Retrospective Studies; Treatment Outcome; Urticaria
PubMed: 37956096
DOI: 10.1093/ced/llad386 -
La Revue Du Praticien Sep 2023BIOTHERAPIES IN SEVERE CHILDHOOD ASTHMA. Asthma is a chronic inflammatory disease of the lower airways and is one of the most common chronic conditions during childhood....
BIOTHERAPIES IN SEVERE CHILDHOOD ASTHMA. Asthma is a chronic inflammatory disease of the lower airways and is one of the most common chronic conditions during childhood. The management of severe asthmatic patients must be multidisciplinary, personalized, and holistic, especially in pediatrics. The therapeutic approach to asthmatic patients has evolved over the last years, targeting inflammatory cells and molecules. Such treatments mainly include biotherapies, and, in children, four monoclonal antibodies are presently available to treat severe asthma: omalizumab, mepolizumab, dupilumab and tezepelumab. These biotherapies have demonstrated short- and medium-term efficacy and safety in both adults and children.
Topics: Adult; Humans; Child; Asthma; Biological Therapy; Antibodies, Monoclonal
PubMed: 37796252
DOI: No ID Found -
Allergy Feb 2024
Eosinophilic granulomatosis with polyangiitis onset in severe asthma patients on monoclonal antibodies targeting type 2 inflammation: Report from the European EGPA study group.
Topics: Humans; Antibodies, Monoclonal; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Asthma; Inflammation
PubMed: 37904674
DOI: 10.1111/all.15934 -
International Immunopharmacology Oct 2023Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunosuppression is an integral part of treating chronic spontaneous urticaria (CSU), but there is no literature to evaluate the efficacy of multiple immunosuppressive agents.
OBJECTIVE
The comparison of the efficacy, safety, and incidence of adverse effects of four immunosuppressive medicines (tripterygium glycosides, methotrexate, cyclosporine A, and azathioprine) in combination with antihistamines in treating CSU provides a clinical reference and evidence-based medicine for treating CSU.
METHODS
PUBMED, The Cochrane Library, EMBASE, WANFANG, CNKI, CBM, and clinical trial registration platform were searched to collect relevant randomized controlled trials (RCT) and cohort studies of four immunosuppressive medicines combined with antihistamines for treating CSU. The primary outcomes were the efficacy of weekly urticaria activity score 7 (UAS7) and adverse effects.
RESULTS
This study pooled data from seven randomized clinical trials with 410 participants. The standardized mean differences for change in UAS7 were 0.10 (95% confidence interval (CI), 0.01 to 0.68) for cyclosporine A plus antihistamine; 0.03 (95% CI, 0.00 to 0.23) for azathioprine plus antihistamine; 0.52 (95% CI, 0.32 to 0.85) for tripterygium glycosides plus antihistamine; and 1.54 (95% CI, 0.64 to 3.67) for methotrexate plus antihistamine. There were no significant differences in side effects between these medicines in the limited number of trials and clinical samples.
CONCLUSION
Our results indicate that cyclosporine A combined with antihistamine resulted in greater improvements regarding the UAS7 in CSU patients and that tripterygium glycosides are also effective in treating CSU.
Topics: Humans; Immunosuppressive Agents; Cyclosporine; Methotrexate; Azathioprine; Network Meta-Analysis; Chronic Disease; Chronic Urticaria; Histamine H1 Antagonists; Urticaria; Histamine Antagonists; Drug-Related Side Effects and Adverse Reactions; Glycosides; Treatment Outcome; Omalizumab; Anti-Allergic Agents; Randomized Controlled Trials as Topic
PubMed: 37567010
DOI: 10.1016/j.intimp.2023.110577 -
Journal of Clinical Immunology Jan 2024The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative,...
The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.
Topics: Child, Preschool; Adult; Child; Humans; Omalizumab; Dermatitis, Atopic; NF-kappa B; Chronic Urticaria; Antibodies, Monoclonal, Humanized
PubMed: 38231347
DOI: 10.1007/s10875-023-01636-y -
Allergy and Asthma Proceedings Nov 2023Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with... (Observational Study)
Observational Study
Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with other mediators of "low-grade inflammation." To compare ET-1, IL-33, the neutrophil-lymphocyte ratio (NLR), eosinophil-lymphocyte ratio (ELR), platelet-lymphocyte ratio (PLR), eosinophil-basophil ratio (EBR), systemic immune inflammation index (SII), and system inflammation response index (SIRI) in patients with chronic spontaneous urticaria (CSU) and are antihistamine sensitive (AHS), antihistamine resistant (AHR), omalizumab sensitive (OmS), and omalizumab resistant (OmR). A prospective observational study enrolled 68 consecutive patients with CSU diagnosed and managed according to the dermatology section of the European Academy of Allergology and Clinical Immunology (EAACI), the European Union funded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization guidelines. Patients with a urticaria control test score of >12 are considered treatment sensitive, and ≤ 12 are considered resistant. The control group consisted of 20 sex-matched subjects without urticarial diseases. Total immunoglobulin E (IgE), antinuclear antibodies (ANA), thyroid stimulating hormone, antithyroid peroxidase, mean platelet volume (MPV), NLR, ELR, PLR, EBR, SII, SIRI, ET-1, and IL-33 were measured at the study entry and compared between the study groups. Thirty AHS group, 38 AHR group, and 20 control group patients were included. The AHS, AHR, and control groups did not differ in demographic parameters, but the CSU groups were characterized by higher indicators of inflammation. In comparison with the AHS group, the AHR group was characterized by higher levels of IL-33 (p = 0.007), ET-1 (p = 0.032), C-reactive protein (p = 0.016), MPV (p = 0.002), and higher rates of positive ANA (p = 0.019). Of the 38 patients from the AHR group, 30 (79%) were included in the OmS group and 8 (21%) were included in the OmR group. The OmR group was characterized by higher levels of C-reactive protein (p = 0.022), EBR (p < 0.001), higher rates of ANA (p = 0.004), and lower levels of ET-1 (p = 0.025) than the OmS group. Our study did not confirm NRL, PRL, SII, and SIRI, PLR as the biomarkers of treatment response to antihistamines and/or omalizumab in CSU. Higher blood levels of IL-33 and ET-1 characterize AHR CSU.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Interleukin-33; Endothelin-1; C-Reactive Protein; Chronic Urticaria; Urticaria; Histamine Antagonists; Histamine H1 Antagonists; Inflammation; Chronic Disease
PubMed: 37919851
DOI: 10.2500/aap.2023.44.230051