Advances in Therapy最新文献

Introduction: Tezepelumab blocks the activity of thymic stromal lymphopoietin, an epithelial cytokine implicated in the pathogenesis of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In a previous analysis, tezepelumab improved asthma and rhinosinusitis symptoms compared with placebo in patients with severe, uncontrolled asthma and a history of CRSwNP in the 2 years before randomization in the NAVIGATOR study. This post hoc analysis of patients with a CRSwNP diagnosis at any time before randomization in NAVIGATOR enabled domain and symptom-specific analyses of Sino-Nasal Outcome Test (SNOT)-22 outcomes.

Methods: Patients (aged 12-80 years) with severe, uncontrolled asthma were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. SNOT-22 total, domain, and item scores were assessed in patients with a history of CRSwNP. Annualized asthma exacerbation rate (primary efficacy outcome), pre-bronchodilator forced expiratory volume in 1 s, and Asthma Control Questionnaire-6, Asthma Quality of Life Questionnaire (standardized) for patients 12 years and older, and Asthma Symptom Diary scores were also assessed in patients with and without a history of CRSwNP.

Results: Of 1059 patients with severe asthma, 165 (15.6%) had a history of CRSwNP. Tezepelumab treatment resulted in sustained improvements versus placebo in SNOT-22 total score throughout the 52-week study period [least-squares mean difference (95% confidence interval) - 11.08 (- 17.80, - 4.35)]. Tezepelumab improved all five SNOT-22 domain scores (sleep, nasal, function, ear/facial, and emotion) and the five SNOT-22 item scores of most clinical interest (decreased sense of smell/taste, nasal blockage, reduced productivity, waking up tired, and cough). Tezepelumab improved asthma-related clinical outcomes in patients with and without a history of CRSwNP.

Conclusion: In patients with severe, uncontrolled asthma and a history of CRSwNP, tezepelumab improved rhinosinusitis symptoms across multiple domains, as well as asthma exacerbations, lung function, asthma control, and health-related quality of life.

Clinicaltrials:

Gov identifier: NCT03347279 ( https://classic.

Clinicaltrials: gov/ct2/show/NCT03347279 ).

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease associated with complications that increase morbidity, such as thrombosis and chronic kidney disease. Limited data exist regarding complications among treated patients outside of clinical trials, especially for patients treated with ravulizumab.

Methods: This study leverages MarketScan claims data to examine the rate of complications in patients receiving PNH treatment. Patients with a diagnosis code of PNH [International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis code: D59.5] between October 2015 and December 2020, aged ≥ 18 on the date of diagnosis, who had a ≥ 6-month follow-up period of continuous enrollment and ≥ 1 PNH-indicated treatment on or after the first PNH diagnosis were included.

Results: Among 211 patients diagnosed with PNH being treated with eculizumab or ravulizumab between October 2015 and December 2020, the most common complications were iron deficiency (20.4% of patients), arterial embolism and thrombosis (16.1%), and chronic kidney disease (11.8%). Overall, 44.1% of patients experienced ≥ 1 complication.

Conclusion: The high number of patients with PNH receiving treatment who nevertheless experienced complications demonstrates significant unmet medical need. Further analysis with larger sample sizes and including newer therapies, such as pegcetacoplan and iptacopan, is required to fully understand the scope and magnitude of this unmet need.

Introduction: This study aimed to describe the clinical characteristics of patients with pulmonary arterial hypertension, treatment received, and factors predicting initial or earlier combination therapy.

Methods: The Adelphi Real World Pulmonary Arterial Hypertension (PAH) Disease Specific Programme™ is a cross-sectional survey with retrospective data collection conducted in the USA, Europe (France, Germany, Italy, Spain, and the UK), and Japan from March to August 2022. Physicians reported patient characteristics, treatment history, and reasons for treatment selection. Descriptive statistics were grouped by country and World Health Organization functional classification. A multivariable Cox regression analysis investigated factors predicting initial or earlier combination therapy use.

Results: Data for 1173 patients was provided by 293 physicians. Patients' mean (standard deviation) age was 58.7 (13.8) years and 54.6% were female. Overall, 91.2% of patients were receiving, or had previously received, PAH-specific treatment. About three-quarters of the cohort were still taking the initial treatment strategy: for this group, 54% were prescribed monotherapy and 32% combination therapy; 15% of patients received supportive therapy alone. The proportion of patients receiving PAH-specific treatment was lowest in the USA (82.0%) and highest in France (94.6%). The proportion of patients receiving PAH on combination therapy was lowest in the USA (23.8%) and highest in Germany (36.5%). Treatment was prescribed for PAH in 87.6%, 89.8%, 89.3%, and 75.0% of patients who were functional class I, II, III, and IV, respectively, and combination therapy usage was more likely for those with more advanced functional class. Higher risk status, care by a pulmonologist, Japanese residence, more complete assessments, and hospitalization in the past 12 months were statistically associated with decreased time to combination therapy for PAH. Older age was statistically associated with increased time to combination therapy.

Conclusion: In this real-world, geographically diverse sample, monotherapy treatment was common, even among patients with advanced disease.

Introduction: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with several treatment options. Some glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the European Medicines Agency include dulaglutide, subcutaneous (s.c.) semaglutide, and oral semaglutide. This study examines dulaglutide and semaglutide dosing patterns for T2DM in France and Italy.

Methods: IQVIA Longitudinal Prescription Data identified adults with T2DM prescribed dulaglutide or semaglutide between August 1, 2020 and December 31, 2022. Cohort 1 (incident) and cohort 2 (prevalent) users were followed for 12 months.

Results: In France and Italy, 255,571 and 350,853 patients, respectively, received at least one study GLP-1 RA. Most dulaglutide-naïve patients in France (62%) and approximately half in Italy (49%) started on 1.5 mg and remained on this dose for up to 12 months (France: 66% cohort 1, 88% cohort 2; Italy: 73% cohort 1, 87% cohort 2). In cohort 1, s.c. semaglutide users mostly started on 0.25 mg (France, 78%; Italy, 61%). At 12 months, s.c. semaglutide 1.0 mg was most prescribed (France: 58% cohort 1, 75% cohort 2; Italy: 59% cohort 2), with cohort 1 in Italy mostly receiving 0.5 mg (57%). Most oral semaglutide users in Italy started on 3.0 mg (78% cohort 1; 68% cohort 2), which was increased to 7.0 mg (62% cohort 1) and 14.0 mg (48% cohort 2) at 12 months.

Conclusions: GLP-1 RA dosing patterns, although similar between France and Italy, were heterogeneous over time. As oral semaglutide and higher dulaglutide doses are recent to the market, additional real-world evidence is required to evaluate utilization patterns. Graphical abstract available for this article.

Introduction: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial.

Methods: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method.

Results: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained.

Conclusions: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.

Introduction: Implantable tibial neuromodulation (iTNM) systems have recently become commercially available in the US, and offer a new method of neurostimulation for the treatment of overactive bladder (OAB). In the absence of head-to-head studies, the aim of this meta-analysis was to indirectly compare the efficacy and safety of sacral neuromodulation (SNM) and implantable tibial neuromodulation (iTNM) for the treatment of OAB.

Methods: A comprehensive search was performed using terms for OAB and neuromodulation. Primary efficacy measures included a ≥ 50% reduction in urgency urinary incontinence (UUI) episodes, urinary frequency, and/or OAB symptoms. Primary safety measures included the rate of device-related adverse events (AEs).

Results: A total of 20 studies met selection criteria, encompassing 1416 patients treated with SNM and 350 patients treated with iTNM. No comparative or placebo-controlled studies for SNM and iTNM were identified, and therefore the analysis was completed using single-arm results. Weighted averages showed that the UUI responder rate was similar for both SNM and iTNM (71.8% and 71.3%, respectively). Similarly, weighted averages of OAB responder rates were 73.9% for SNM and 79.4% for iTNM. Similar rates of device-related AEs were also observed.

Conclusions: This meta-analysis found similar efficacy and safety of SNM and iTNM for the treatment of OAB and UUI, including UUI and OAB symptom response rates, reduction in UUI episodes, significant improvements in quality-of-life (QoL), and low rates of procedure and device-related adverse events. Notably, this comparable efficacy was seen without the use of a trial phase of neuromodulation in the iTNM studies versus SNM studies.