Effect of individual allergen sensitization on omalizumab treatment outcomes in patients with severe allergic asthma determined using data from the Czech Anti-IgE Registry.

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.

Use of dupilumab in a patient with atopic dermatitis, severe asthma, and HIV infection.

Dupilumab is a monoclonal antibody against interleukin 4 (IL-4) receptor α that blocks signaling from IL-4 and IL-13, essential mediators of T helper 2 (Th2) pathway. To date, all clinical trials investigating the use of dupilumab excluded patients with human immunodeficiency virus. Herein, we describe the safe and successful use of dupilumab in a patient with atopic dermatitis, severe therapy resistant asthma, and HIV infection.

Serum periostin levels in asthma patients in relation to omalizumab therapy and presence of chronic rhinosinusitis with nasal polyps.

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.

Four seasons of Czech asthma study: asthma characteristics and management reality in the Czech Republic.

Objective: To describe the characteristics and management of asthma in clinical practice in the Czech Republic in the context of international guidelines and clinical realities.Methods: Data were collected over four seasons from summer 2016 to spring 2017 and are mostly presented using descriptive statistics.Results: We obtained valid data for 4557 adult patients with asthma, including detailed phenotyping (71% eosinophilic allergic, 10% eosinophilic non-allergic, 19% non-eosinophilic non-allergic asthma) from 58 allergologists and 56 pulmonologists. The average time to diagnosis was 3 years. In more than half of the subjects, bronchodilator testing (BDT) results were available at primary diagnosis. More than 10% of physicians did not test for mold allergy. Occupational asthma was diagnosed in 0.7% of subjects. According to the attending physician, 68% of patients had well-controlled and 10% had uncontrolled asthma. Ninety-four percent of patients were on preventive treatment, with 91% using an inhaled corticosteroids (ICS) at an average dose of 705 µg/day budesonide equivalent. Approximately 75% of patients were on an ICS/LABA, with 91% using fixed combinations. Among patients using ICS/formoterol, a maintenance and reliever therapy regime was prescribed in 67%.Conclusions: The quality of asthma management in the Czech Republic is comparable to that of other developed countries and better in some respects (frequent BDT, phenotyping, and use of preventive treatment). Nevertheless, there is unnecessary delay in diagnosis and lack of research on possible environmental causes (workplace, molds). Pharmacotherapy shows good adherence to guidelines. Although 10% of patients show poor control, there is concurrently a trend for overtreatment.

Real-world effectiveness and safety of omalizumab in patients with uncontrolled severe allergic asthma from the Czech Republic.

INTRODUCTION: This was a sub-group analysis of patients with uncontrolled persistent allergic asthma (AA) in the healthcare setting of the Czech Republic, from a global non-interventional, 2-year post-marketing, observational eXpeRience registry. AIM: To evaluate the real-life effectiveness and safety of omalizumab. MATERIAL AND METHODS: Patients with uncontrolled persistent AA (currently defined by the Global Initiative for Asthma (GINA) as uncontrolled severe AA) who started omalizumab treatment 15 weeks before inclusion in the registry were analysed for physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms, corticosteroid use, exacerbation rate, asthma control, quality of life, healthcare utilisation and safety during a 24-month observation period. RESULTS: One hundred and fourteen patients from the Czech Republic were enrolled in the eXpeRience registry. A total of 88.9% of the patients were evaluated as responders to omalizumab according to the GETE assessment at week 16. From baseline to month 24: mean change in forced expiratory volume in 1 s (FEV1) was 137 ml and the daily dose of OCS decreased (11.6 mg to 6.4 mg prednisolone equivalent); the percentage of patients with no severe clinically significant exacerbations increased (29.5% to 95.1%); Asthma Control Test scores improved (12.4 to 17.3) and mean total number of days of asthma-related medical healthcare use decreased (6.8 days to 0.4 days). CONCLUSIONS: The results of this subgroup analysis support the evidence that add-on omalizumab therapy is effective and well tolerated for management of patients with uncontrolled persistent AA in the Czech Republic. Global evaluation of treatment effectiveness assessment is a reliable predictor of long-term response to omalizumab treatment.

[Asthma bronchiale in the context of internal medicine]. / Asthma bronchiale v kontextu vnitrního lékarství.

The article is supposed to give a modern perspective on etiopatogenesis of asthma and its management. There are accentuated new diagnostics and treatment opportunities as well as coincident areas with others internal fields and pragmatic recommendation for daily clinical practice.Key words: allergy - asthma heterogeneity - asthma management - eosinophilia - internal medicine - phenotype-specific therapy - stepwise pharmacotherapy.