Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL-1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in 1 s (FEV1) and patient-reported outcomes. Of 953 patients, 69% (n=657) and 11% (n=106) were receiving Step 4 and Step 5 therapy, respectively. Compared with placebo, reslizumab reduced exacerbation rates by 53% (95% CI 0.36-0.62) and 72% (95% CI 0.15-0.52), in Step 4 and Step 5 groups respectively. By study end, reslizumab increased FEV1 in Step 4 and Step 5 groups by 103 mL (95% CI 52-154 mL) and 237 mL (95% CI 68-407 mL), respectively. Reslizumab also improved patient-reported outcomes compared with placebo in both groups. Reslizumab reduces exacerbation rates and improves lung function and patient-reported outcomes in patients with eosinophilic asthma receiving therapy per Steps 4 and 5 of the GINA guidelines

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Clinical application of a simple questionnaire for the differentiation of asthma and chronic obstructive pulmonary disease

AbstractBackground: Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic diseases characterized by airflow limitation. Both diseases have a distinct pathogenesis and require unique treatment approaches. Due to some common characteristic traits, asthma and COPD are often lumped together in clinical practice. We sought to develop a simple questionnaire for the distinction of asthma and COPD.Methods: Clinical discriminants of asthma and COPD were retrospectively identified by multiple logistic regression using files from 547 consecutive adult patients presenting to a pulmonary specialist practice with a diagnosis of asthma or COPD. With these features, we generated a simple quantitative questionnaire supporting a diagnosis of COPD with high scores and asthma with low scores (range 0–15 points). Questionnaire results were compared with physician's diagnosis based on GINA and GOLD guidelines including skin tests, spirometry and reversibility data.Results: 210 patients had COPD and 337 had asthma. Age of onset, smoking history, atopy status, and cough quality were significantly associated with a diagnosis of asthma or COPD. Questionnaire scores for COPD patients were higher than those for asthmatics (mean score 10.5±0.18 vs. 4±0.12, P<0.0001). Receiver operational characteristics (ROC) analysis revealed a cutoff score of 7 with the highest discriminant power (87.6% sensitivity, 87.2% specificity for COPD, 87.4% correctly classified, area under the ROC curve: 0.954). The overlap between asthma and COPD (score 6–8) comprised about 20% of the total population, these patients included a higher proportion of COPD patients with atopy, and smoking asthmatics.Conclusions: In patients with obstructive airway diseases, a simple questionnaire can support the differentiation of asthma and COPD in everyday clinical practice. Further prospective trials are necessary to confirm these initial observations

Asthma exacerbations and worsenings in patients aged 1-75 years with add-on tiotropium treatment

This review explores the effect of tiotropium Respimat® add-on therapy on asthma exacerbations and worsenings, adverse events (AEs) related to exacerbations and symptoms and any effects on seasonality across the 10 UniTinA-asthma® clinical trials comprising over 6000 patients. When added on to inhaled corticosteroids ± additional therapies, tiotropium significantly reduced the risk of exacerbations and worsenings in adults with symptomatic severe asthma and provided a non-significant improvement in worsenings in adults with symptomatic moderate and mild asthma, which was significant for patients with moderate asthma receiving tiotropium 2.5 µg once daily vs. placebo. Trials in paediatric patients were not powered to assess exacerbations or worsenings, but when AEs related to asthma exacerbations and symptoms were grouped into a composite endpoint and pooled, tiotropium improved outcomes vs. placebo (rate ratio 0.76; 95% confidence interval 0.63, 0.93). The reduction in exacerbations with tiotropium is apparent across all patients during the observed seasonal peaks of these events

Long-term safety of tiotropium/olodaterol Respimat® in patients with moderate-to-very severe COPD and renal impairment in the TONADO® studies

Introduction: The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO (R) studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. Methods: These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat (R)) in patients with moderate-to-very severe COPD. In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60-89 mL/min), moderate (CLcr 30-59 mL/min) or severe (CLcr 15-29 mL/min). Adverse events (AEs) were pooled from both studies. Results: Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups. Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively. There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents. There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment. Conclusion: Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular comorbidity. The safety and tolerability of tiotropium/olodaterol is comparable to the monocomponents, irrespective of the level of renal impairment

Omalizumab as alternative to chronic use of oral corticosteroids in severe asthma

Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective alternatives. Fortunately, in the last decade several biologics have been proven safe and effective for patients with uncontrolled severe asthma. This has led to the Global Initiative for Asthma (GINA) recommending the use of biologics, instead of maintenance OCS, in patients with severe asthma (GINA Step 5). These include one biologic targeting immunoglobulin E (IgE) (omalizumab), and different biologics targeting interleukin-5 (IL-5), the IL-5 receptor (IL-5R) or IL-4 receptor alpha-unit (IL-4R alpha), including mepolizumab (subcutaneous), reslizumab (intravenous), benralizumab (subcutaneous) and dupilumab (subcutaneous). Omalizumab for the treatment of severe allergic asthma reduces exacerbations, irrespective of blood eosinophil levels. Anti-IL-5/IL-5R biologics are indicated in patients with severe eosinophilic asthma and repetitive exacerbations, irrespective of the presence or absence of allergy. Recently, an anti-IL4R alpha biologic has been approved by the FDA for eosinophilic phenotype or oral corticosteroid-dependent asthma. Finally, physicians should consider using biologics as an alternative to chronic OCS therapy

Efterårsferie i regnbuens farver

I dagene 13.-21. oktober sætt er Steno Museet fokus på regnbuen og dens farver. Hvad er en regnbue, hvordan ser den ud, og i hvilken rækkefølge kommer farverne

Indacaterol vs tiotropium in COPD patients classified as GOLD A and B

SummaryIntroductionAccording to current GOLD strategy, patients with COPD classified as groups A and B may be treated with inhaled bronchodilators, either long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA). However, there is little guidance on which class of agent is preferred and a lack of prospective data to differentiate the two.MethodsIn this study, we performed post-hoc analyses of pooled data from two prospective, controlled clinical trials comparing the LABA indacaterol and LAMA tiotropium in 1422 patients with moderate airflow limitation and no history of exacerbations in the previous year. This population fits the definitions of GOLD A and B groups and could be further stratified by symptom severity using Baseline Dyspnea Index (i.e. modeling GOLD A or B) and inhaled corticosteroid (ICS) use at baseline. Outcomes measured after 12 weeks of treatment were lung function (forced expiratory volume in 1 s; FEV1), health status (St George's Respiratory Questionnaire; SGRQ), symptoms (Transition Dyspnea Index; TDI) and rescue medication use.ResultsIn ‘GOLD A’ patients not receiving ICS, differences favored indacaterol versus tiotropium (trough FEV1 0.05 L; rescue medication use −0.41 puffs/day; TDI total score 0.94 points; SGRQ total score −3.13 units, all p < 0.01). In ‘GOLD B, no ICS’ patients, compared with tiotropium, indacaterol treatment increased trough FEV1 (0.055 L, p < 0.05) and permitted a larger reduction in rescue medication use (−0.81 puffs/day, p = 0.004). In all patients, and in patients not using ICS, differences favored indacaterol for all variables.ConclusionsOur findings suggest that patients in GOLD groups A and B may experience greater benefits with indacaterol than with tiotropium