- Publication type
- Meeting Abstract MeSH
Background: Omalizumab is an efficient drug for patients with uncontrolled severe allergic asthma (SAA). However, little is known about the differences in omalizumab treatment outcomes among patients with different types of atopic sensitization. Here, we assessed the effect of sensitization to individual allergens or their combinations on the outcomes of anti-IgE therapy in patients with SAA. Methods: We performed a post hoc analysis of data of subgroups of patients enrolled in the Czech Anti-IgE Registry (CAR). The patients were evaluated at baseline and 16 weeks and 12 months after omalizumab treatment initiation. We analyzed the dependence of primary treatment outcomes [global evaluation of treatment effectiveness (GETE) after 16 weeks of treatment, a reduction in severe exacerbation rate (ER), and an improvement in the asthma control test (ACT) result during 12 months of treatment] and secondary outcomes [a reduction in systemic corticosteroid (SCS) use, an improvement in lung functions, and a fraction of exhaled nitric oxide] of patients with SAA treated with omalizumab for 12 months on sensitization to different perennial aeroallergens. We assessed sensitization to house dust mites, molds, and pets at baseline using skin prick tests and/or specific IgE measurement (semiquantitative evaluation). We compared polysensitized patients (sensitized to all tested allergens) with monosensitized (single positivity) or partially polysensitized patients (combined positivity but not to all allergens). Results: We enrolled 279 patients (58.3% women, mean age 52.9 years). Omalizumab treatment presented an 82.8% response rate (according to GETE). It significantly reduced severe asthma exacerbations and SCS use, and improved the ACT result in 161 responders. We identified a subgroup of responders with distinct sensitization patterns (polysensitization to all tested perennial allergens) with higher odds of being responders (OR = 2.217, p = 0.02) and lower tendency to improve ACT result (OR 0.398, p = 0.023) and reduce ER (OR 0.431, p = 0.034) than non-polysensitized patients. Conclusions: The clinical benefit of sensitization for patients with SAA receiving omalizumab may be particularly dependent on sensitization pattern. Polysensitized patients showed a higher tendency to be responders (GETE), but a lower tendency to improve the ACT result and reduce ER than non-polysensitized patients.
- Publication type
- Journal Article MeSH
Introduction: The serum periostin level is a promising biomarker of type 2- high inflammation pattern of bronchial asthma. It has been proven that serum periostin levels decrease in response to systemic and inhaled corticosteroid (ICS) therapy. However, we have only limited knowledge about changes in serum periostin levels reflecting omalizumab (OMA) treatment and other variables, such as chronic rhinosinusitis with nasal polyps (CRSwNP). Aim: To critically appraise clinically relevant parameters influencing periostin levels in asthma patients. Material and methods: A pilot, cross-sectional, observational study to assess serum periostin levels of 48 asthma patients (38 treated by conventional therapy comprising ICS and 10 treated by ICS and OMA as an add-on therapy) with respect to asthma clinical traits, comorbidities and to other biomarkers of type 2-high asthma phenotype (total IgE, absolute and relative eosinophil count, eosinophilic cationic protein (ECP) and a fraction of exhaled NO (FeNO)). Results: Serum periostin correlates with total IgE levels (Spearman rho = 0.364, p = 0.025) in a subgroup of conventionally treated patients, and with eosinophil count (Spearman rho = 0.401, p = 0.021) in a subgroup of patients with concurrent CRSwNP. Serum periostin levels were decreased in omalizumab-treated patients in comparison to conventionally treated patients (p = 0.025). This effect was remarkably apparent only if CRSwNP was not present (p = 0.005). Conversely, we measured elevated periostin levels in OMA-treated patients with concurrent CRSwNP (p = 0.017). Conclusions: Serum periostin production is significantly associated with treatment modality (omalizumab vs. conventional) and presence of CRSwNP. These variables need to be taken into account to interpret periostin levels accurately.
- Publication type
- Journal Article MeSH
Léčba anti IgE monoklonální protilátkou omalizumabem je schválená pro léčbu těžkého alergického bronchiálního astmatu a chronické spontánní kopřivky. Efekt léčby omalizumabem byl však pozorován i u jiných IgE zprostředkovaných onemocnění. Cílem této studie je posouzení účinku omalizumabu na kontrolu astmatu a alergických onemocnění u pacientů s těžkým alergickým astmatem zařazených do projektu CAR (Czech Anti-IgE Registry). Do registru CAR bylo zařazeno celkem 310 pacientů s těžkým alergickým astmatem léčených omalizumabem celkem v 10 centrech v České republice v letech 2006–2015. U 229 nemocných byl po 12 měsících terapie hodnocen efekt léčby omalizumabem na klinické projevy bronchiálního astmatu (test kontroly astmatu (ACT), vyšetření koncentrace oxidu dusnatého ve vydechovaném vzduchu (FENO, spirometrie), užívání systémové kortikoterapie a symptomy dalších komorbidit – alergické rinitidy (n = 203), atopické dermatitidy (n = 67), potravinové alergie (n = 58) a chronické kopřivky (n = 14). Po 12 měsících léčby omalizumabem došlo k signifikantnímu zlepšení hodnot ACT, forsírovaného expiračního objemu za 1s a FENO, poklesu počtu aplikací terapie systé-movými kortikosteroidy z důvodu exacerbace astmatu a snížení průměrné denní dávky dlouhodobé systémové kortikoterapie. Pozitivní účinek léčby omalizumabem jsme pozorovali u 82,2 % pacientů s alergickou rinitidou (zlepšení u 63,5 % nemocných, úplné vymizení příznaků u 18,7 % pacientů). U 46,3 % pacientů bylo zjištěno zlepšení projevů atopické dermatitidy a 35,8 % nemocných nemělo žádné projevy kožní nemoci. Zlepšení chronické kopřivky bylo zaznamenáno u 50 % nemocných a kompletní remise u 35,7 % jedinců. U po-travinové alergie udávalo zlepšení 27,6 % nemocných a u 39,7 % pacientů symptomy úplně ustoupily. V registru CAR pacientů s těžkým alergickým astmatem léčených omalizumabem byl zjištěn pozitivní efekt anti IgE terapie nejenom na klinický průběh astmatu, ale i na další alergické komorbidity. Většina pacientů s alergickou rinitidou, atopickou dermatitidou, chronickou kopřivkou a potravinovou aler-gií zaznamenala zlepšení nebo kompletní remisi projevů těchto onemocnění. Nejnižší efektivita léčby byla pozorována u potravinové alergie.
The treatment with anti-IgE monoclonal antibody omalizumab is approved for severe allergic asthma (SAA) and chronic spontaneous urticaria. However, the effectiveness of omalizumab has been observed also in other IgE-mediated diseases. The aim of this study was to evaluate the effect of omalizumab on SAA and other allergic comorbidities in the group of patients treated with omalizumab for SAA enrolled in the Czech Anti-IgE Registry (CAR). 310 patients with SAA treated with omalizumab were enrolled to the CAR in 10 specialised centres in the Czech Republic between the years 2006 and 2015. 229 individuals were evaluated after 12 months of omalizumab therapy for asthma control test (ACT), examination of fractional exhaled nitric oxide (FENO), forced expiratory volume in 1 second (FEV1), the use of systemic corticosteroids, side effects of therapy and clinical effect of omalizumab on allergic comorbidities – allergic rhinitis (n = 203), atopic dermatitis (n = 67), food allergy (n = 58), and chronic urticaria (n = 14). A significant improvement of ACT and FEV1, reduction of FENO, use of systemic corticosteroids for asthma exacerbations and dose of maintenance oral corticosteroid therapy were observed after 12 months of treatment with omalizumab. The positive effect of therapy was observed in 82.2% of patients with allergic rhinitis (improvementin 63.5% of patients, complete remission in 18.7% of patients). 46.3% of patients with atopic dermatitis experienced improvement of symptoms and in 35.8% of patients atopic dermatitis completely resolved. In 35.7% of patients, chronic urticaria disappeared during the therapy with omalizumab and it improved in 50.0% of patients. Complete remission of food allergy was reported in 39.7% of patients and improvement in 27.6% of patients. In the CAR registry, patients with SAA treated with omalizumab showed a significant positive effect of anti-IgE therapy not only on the asthma control, but also on allergic comorbidities. The majority of patients with allergic rhinitis, atopic dermatitis, chronic urticaria and food allergy experienced improvement or complete remission of symptoms. The lowest effectiveness of omalizumab treatment was observed in food allergy.
- Keywords
- CAR,
- MeSH
- Rhinitis, Allergic drug therapy MeSH
- Dermatitis, Atopic drug therapy MeSH
- Asthma drug therapy therapy MeSH
- Immunoglobulin E immunology MeSH
- Humans MeSH
- Omalizumab * adverse effects therapeutic use MeSH
- Food Hypersensitivity drug therapy MeSH
- Urticaria drug therapy MeSH
- Check Tag
- Humans MeSH
Článek se zaměřuje na biologickou léčbu těžkého alergického astmatu, především na léčbu anti-lgE protilátkou omalizumabem, se kterou je celosvětově nejvíce zkušeností. Jsou shrnuty dosavadní poznatky o výsledcích léčby i s využitím dat z národního registru CAR (Czech Anti-lgE Registry).
This article focuses on the biologic treatment of severe allergic bronchial asthma, especially the treatment with anti-IgE antibody omalizumab, with which is the most worldwide experience. The present knowledge of treatment results is summarized, also using data from our national register (Czech Anti-IgE Registry, CAR).
- MeSH
- Hypersensitivity MeSH
- Biological Therapy * MeSH
- Asthma * complications MeSH
- Humans MeSH
- Antibodies, Monoclonal MeSH
- Omalizumab MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Autoři popisují diagnostiku a terapii 39leté nekuřačky s metastazujícím adenokarci - nomem pravého horního plicního laloku. Imunohistochemicky a metodou FISH (fluorescenční in situ hybridizace) byla jako řídící mutace v nádoru prokázána přestavba genu ROS1, varianta CD-74ROS1. Nemocné byla podána cílená terapie krizotinibem, v jejím průběhu došlo k regresi nádorových ložisek. Zbytková léze v pravém horním plicním laloku byla odstraněna chirurgicky, nemocná je v dobrém stavu, opět vykonává svoji profesi a pokračuje v cílené léčbě ROS1 inhibitorem 1. generace, zatím celkem 16 měsíců od zahájení léčby.
The authors present a diagnostic procedure and a treatment of 39-year-old non-smoker patient with a metastatic adenocarcinoma of the right upper lobe of lung. Immuno - histochemistry and FISH (fluorescent in situ hybridization) method detected a rearrangement of ROS1 gene, CD-74ROS1 variant, as a cancer driver mutation. The patient was treated with crizotinib as a targeted therapy. Cancer lesions regressed during the therapy. The residual lesion in the right upper lobe of lung was surgically removed. The patient is in a good clinical condition, she returned to her original work. She has been receiving a targeted therapy with the first-generation ROS1 inhibitor for 16 months since the ini - tiation of the treatment so far.
- Keywords
- přestavba genu ROS1,
- MeSH
- Adenocarcinoma of Lung * drug therapy surgery pathology MeSH
- Biological Therapy MeSH
- Molecular Targeted Therapy MeSH
- Adult MeSH
- In Situ Hybridization, Fluorescence MeSH
- Immunohistochemistry MeSH
- Crizotinib * therapeutic use MeSH
- Humans MeSH
- Carcinoma, Non-Small-Cell Lung * diagnosis pathology therapy MeSH
- Positron Emission Tomography Computed Tomography MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Jednu z nejtěžších forem astmatu představuje astma spojené s alergickou přecitlivělostí vůči plísním. V těchto případech často selhává nejen 4. stupeň paušální stupňovité léčby, ale v řadě případů i možnosti 5. stupně léčby dle GINA, jako jsou systémová kortikoterapie a/nebo cílená biologická léčba. Uvedené léčebné modality totiž nejsou schopny ovlivnit ojedinělé specifikum této formy astmatu: skutečnost, že zdroj alergenu, tj. plíseň, kolonizuje dýchací cesty nemocného. Komplexní léčba těchto nemocných v centrech pro těžké astma proto zahrnuje i léčbu antimykotiky. Ani tato léčba však nevede u všech pacientů k uspokojivým výsledkům, navíc je zatížena rizikem nežádoucích účinků a je finančně nákladná. Ve snaze o redukci dávek a délky podávání antimykotik jsme proto u vybraných pěti nemocných doplnili léčbu antimykotiky podáváním systémové enzymoterapie. U celkem tří pacientů jsme dosáhli zřetelného zlepšení klinické odpovědi, u zbývajících dvou nemocných jsme efekt systémové enzymoterapie (pozitivní ani negativní) nezaznamenali. Předkládaná kazuistika popisuje jednu z našich pozitivních zku- šeností a diskutuje pro/kontra.
Bronchial asthma associated with fungal hypersensitivity is one of the most severe asthma types. Both the Step 4 of step-wise asthma treatment strategy, but in many patients also the Step 5 of GINA recommended therapeutic approach, such as systemic corticosteroids and/or targeted biological treatment, often fail in those cases. The above mentioned therapeutic modalities are not able to influence the rare specificity of this asthma type represented by the fact that the source of allergen, i.e. mould, colonizes patient’s airways. Therefore, complex treatment of such patients in severe asthma centres also includes antimycotic drugs. However, even this medication does not provide favourable outcomes in all patients. Moreover, there is a risk of adverse reactions and it is also expensive. In an effort to reduce doses and duration of the antimycotic therapy we augmented the antimycotic therapy with the systemic enzyme therapy in 5 selected patients. The marked improvement of clinical condition was achieved in three patients, while no effect of systemic enzyme therapy (either positive or negative) was observed in other two patients. This case report describes one of our positive experiences and discuss the pros and cons.
- MeSH
- Hypersensitivity diagnosis immunology MeSH
- Antifungal Agents MeSH
- Administration, Inhalation MeSH
- Biological Therapy MeSH
- Asthma * diagnosis drug therapy MeSH
- Bronchodilator Agents MeSH
- Celiac Disease diagnosis MeSH
- Hydro-Lyases administration & dosage therapeutic use MeSH
- Enzyme Therapy * MeSH
- Esophagitis diagnosis drug therapy MeSH
- Glucocorticoids MeSH
- Adrenal Cortex Hormones administration & dosage therapeutic use MeSH
- Fungi * immunology pathogenicity MeSH
- Itraconazole administration & dosage therapeutic use MeSH
- Fluticasone-Salmeterol Drug Combination administration & dosage therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Methylprednisolone administration & dosage therapeutic use MeSH
- Pneumonectomy MeSH
- Disease Progression MeSH
- Tiotropium Bromide administration & dosage therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Adenocarcinoma of Lung * drug therapy genetics MeSH
- Antineoplastic Agents therapeutic use MeSH
- Adult MeSH
- In Situ Hybridization, Fluorescence methods MeSH
- Crizotinib therapeutic use MeSH
- Humans MeSH
- Carcinoma, Non-Small-Cell Lung drug therapy genetics MeSH
- Positron Emission Tomography Computed Tomography methods MeSH
- Antineoplastic Protocols MeSH
- Proto-Oncogene Proteins genetics MeSH
- Translocation, Genetic MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Publication type
- Meeting Abstract MeSH
- Publication type
- Meeting Abstract MeSH
