Drugs - Real World Outcomes最新文献

Background: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor was licensed for the treatment of ALK-positive metastatic non-small cell lung cancer in 2016. However, real-world evidence on the safety and effectiveness of brigatinib in Latin America remains limited.

Objective: The aim of this study was to assess the safety and effectiveness of brigatinib in the real world in Argentina.

Methods: We conducted a non-interventional cohort study of adult patients (aged ≥  18 years) with a diagnosis of ALK-positive metastatic non-small cell lung cancer not previously treated (first line) or previously treated (second line) with an ALK inhibitor and who received at least one dose of brigatinib between November 2020 and March 2023. The primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes at the 24-week follow-up were the percentage of patients with an overall best objective response rate of complete or partial response; intracranial objective response rate; progression-free survival; and overall survival.

Results: Of the 39 patients included in the study (n = 22 [first line]; n = 17 [second line]), 12 patients (30.7%) experienced treatment-emergent adverse events, with the most frequent being increased levels of transaminases (7.6%), increased level of blood creatine phosphokinase (5%) and hypokalaemia (5%). Most adverse events (85.7%) were mild to moderate. Effectiveness outcomes at 24 weeks in patients treated with brigatinib first line or second line, respectively, were as follows: overall objective response rate: 81.8% and 70.5%; intracranial objective response rate (in patients with brain metastases at baseline): 66.6% and 88.8%; progression-free survival: 93.8% and 82.4%; overall survival: 100% and 87.5%.

Conclusions: Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in routine clinical practice in Argentina.

Clinical trial registration: NCT04887519.

Background: In early 2022, new treatment recommendations for heart failure (HF) were introduced in Sweden.

Objective: This study aims to evaluate and analyze the pharmaceutical treatment patterns of HF patients over time in Sweden, in relation to the updated treatment recommendations.

Methods: This observational study is based on registry data. The study population consisted of patients ≥18 years old who, at any time between 2017 and 2023, had an HF diagnosis, defined using ICD-10 code I50 (n = 212,757). Descriptive statistics were presented for the study population. Based on data from the national drug prescription registry, the treatment patterns between 2021 and 2023 were analyzed using biannual datasets before and after the introduction of treatment recommendations.

Results: The mean age of the study population was 79 years and 56% were men. The utilization of quadruple therapy and SGLT2 inhibitors, both as monotherapy and in combination, increased over time, with a rising trend already apparent prior to the introduction of the updated treatment recommendations. At the end of 2023, about 30% of the incident HF population had at least tried quadruple therapy. Furthermore, a growing number of diverse treatment pathways among HF patients was observed over time, which may indicate an increased consideration for individualized treatment.

Conclusions: Even though the implementation of the treatment recommendations for HF is not yet optimal, this study found a notable adoption of quadruple therapy in Sweden. There was an increased use of SGLT2 inhibitors and quadruple therapy, beginning even before the introduction of the updated Swedish treatment recommendations.

Background: Multiple sclerosis (MS) is a heterogeneous disease that may manifest differently among racial/ethnic groups, influencing response to disease-modifying therapy (DMT). Data on natalizumab (NTZ) effectiveness in people with MS (PwMS) based on race/ethnicity are limited.

Objective: The aim of this study was to evaluate the effectiveness of NTZ on relapse onset and rate, and to assess MS-related healthcare encounters and costs in Black, Hispanic, Asian, and White PwMS.

Methods: This was a retrospective analysis of the Komodo Health Claims Database, including adult patients in the US with one or more MS claim at index date (January 1, 2016-August 31, 2022). Patients were followed from first NTZ exposure through end of study, end of insurance eligibility, gap in index DMT > 45 days, or DMT switch. Annualized relapse rate (ARR), time to first relapse, and MS-related healthcare encounters and costs were compared in the 12 months pre/post NTZ initiation and while on treatment across racial strata.

Results: The study included 3244 PwMS (Black, n = 632; Hispanic, n = 382; Asian, n = 49; White, n = 2181). Mean post-index NTZ exposure was 15.5-19.2 months. Post-index ARRs were significantly reduced across racial/ethnic groups (p < 0.001). The adjusted Kaplan-Meier estimated proportion of relapse-free patients at 2 years for all racial/ethnic groups was not significantly different from the White group. Significant differences were observed in annualized MS-related healthcare cost rates but not in annualized MS-related encounter rates before and after NTZ initiation across the racial/ethnic groups.

Conclusion: NTZ was effective across racial/ethnic groups although not significantly different between groups.

Background: Immunotherapy has altered the treatment landscape for resectable non-small cell lung cancer, increasing the complexity of treatment planning. Understanding treatment patterns and outcomes prior to the advent of immunotherapy can provide context for assessing the benefit of immunotherapies and other novel agents.

Objective: We aimed to characterize real-world demographics, clinical characteristics, treatment patterns, and clinical outcomes of patients with early-stage non-small cell lung cancer before widespread immunotherapy use.

Methods: Analyses included patients from the US CancerLinQ Discovery^® database diagnosed with stage I-III non-small cell lung cancer between 2014 and 2020 without known EGFR mutations who underwent surgical resection within 140 days of diagnosis. The primary outcome was treatment patterns by disease stage.

Results: Analyses included 3077 patients with stage I (n = 1673), II (n = 853), and III (n = 551) disease. Most (92.8%, 52.3%, and 36.5% of stage I, II, and III patients) received surgery without systemic therapy. Among stage I, II, and III patients, 7.2%, 44.8%, and 46.6% received adjuvant therapy only. Of stage II and III patients, 2.0% and 10.2% received neoadjuvant therapy only, and 0.9% and 6.7% received both (stage I patients who received neoadjuvant only or perioperative therapy were excluded because of low numbers [n = 4]). Five-year overall survival rates were 73.4%, 61.9%, and 50.5% in stage I, II, and III patients; 5-year real-world relapse-free survival rates were 35.4%, 23.1%, and 14.0%. In an exploratory multivariate analysis, neoadjuvant treatment was associated with improved overall survival and real-world relapse-free survival in stage II-III patients (stage I patients not evaluable). Adjuvant treatment was associated with improved real-world relapse-free survival, but not overall survival, in stage II-III patients.

Conclusions: Most patients received surgery alone, though the proportion receiving systemic treatment increased with disease stage. Modest 5-year, real-world relapse-free survival rates indicate a need for more effective neoadjuvant or adjuvant treatments in this setting.

Background and objectives: Extended follow-up data from real-world cohorts of patients with multiple sclerosis treated with ocrelizumab (OCR) are becoming widely available. This monocentric retrospective study aimed to evaluate the long-term effectiveness of OCR and its impact on immunoglobulin (Ig) levels, lymphocyte subsets, and infections in a cohort of patients with relapsing remitting, primary progressive, and secondary progressive multiple sclerosis.

Methods: Patients followed at the Multiple Sclerosis Center of Bari with ≥ 2 years of OCR treatment were retrospectively recruited in 2024. Twelve-month confirmed disability worsening, improvement, and the annualized relapse rate before and after treatment start were estimated and follow-up magnetic resonance imaging scans were collected. Changes in IgG/IgM/IgA levels from baseline for up to 6 years of OCR treatment and serum levels of T CD4+, T CD8+, and natural killer lymphocytes were assessed. Infection occurrence, type, and outcomes were investigated. Multivariable Cox models examined the association of clinical and radiological baseline factors with the risk of confirmed disability worsening and the relationship of infections with clinical-laboratoristic risk factors.

Results: The final cohort retrieved 140 patients (80 relapsing remitting, 37 primary progressive, 23 secondary progressive) with a median (interquartile range) follow-up after treatment start of 4.62 (4.10-5.04) years. In the entire cohort, the mean annualized relapse rate decreased from 0.61 in the year before the start of OCR treatment to 0.02 in the second year, thereafter all patients in our cohort remained free of relapses and magnetic resonance imaging activity. The overall percentage of stable patients increased from the second to the fourth year, in parallel with a reduction in patients with confirmed disability worsening. A multifocal onset and the presence of at least two relapses before the start of OCR treatment were significant (p < 0.05) risk factors of confirmed disability worsening. During the follow-up, a reduction in the IgG serum level was observed, which further decreased, becoming stable after the third year. Immunoglobulin M levels slightly decreased over time, whereas IgA levels remained stable. No changes for T CD4+, natural killer cell absolute number, and a slight reduction in T CD8+ lymphocytes during follow-up were observed. Ocrelizumab did not determine a significant infection risk in the long term and no association was observed with Ig levels and severe infections.

Conclusions: Ocrelizumab prevented disease activity over the long term and its effect on the immune system did not determine a significant infection risk in most patients.

Background: The advent of biologics has expanded treatment options for Crohn's disease (CD). This study assessed treatment patterns in pediatric and adult patients with CD in the United States during 1- and 3-year follow-up periods.

Methods: This retrospective, claims-based cohort study utilized the Merative™ MarketScan^® Research Databases from January 1, 2014, to December 31, 2021. The index date was the date of the first CD diagnosis during the identification period. Among pediatric and adult CD cohorts, patients were stratified into two subgroups: (a) previously diagnosed (presence of a CD claim) and (b) newly diagnosed (absence of a CD claim) in the 12-month pre-index period. Results were summarized descriptively.

Results: Data from 2809 pediatric and 25,940 adult patients were analyzed at 1-year follow-up. Mean age in years was 13.5 for pediatric and 46.0 for adult patients. Combination therapies were more common in pediatric versus adult patients, especially among those newly diagnosed with CD (38.2% vs 13.9%). A higher percentage of pediatric patients were prescribed biologics than adults (35.1% vs 24.3%). Numerically shorter time from diagnosis to corticosteroid initiation was observed in pediatric versus adult patients (9.5 vs 35 days). Higher persistence to biologics was observed in pediatric versus adult patients (94.6% vs 87.1%).

Conclusions: Combination therapies with biologics were more frequent among pediatric patients than adults. Although the overall treatment pattern among pediatric and adult patients was similar, early initiation of corticosteroids and adoption of biologics were more frequently observed in pediatric than adult patients, consistent with pediatric CD presenting with more aggressive disease.

Introduction: High levels of low-density lipoprotein-cholesterol (LDL) is a major risk factor for cardiovascular diseases. While treatment with atorvastatin is beneficial, the original atorvastatin may be cost prohibitive to some patients. Currently, a second brand of generic atorvastatin is available on the market. This study aimed to evaluate the effectiveness of the second generic brand of atorvastatin.

Methods: This was a retrospective cohort study conducted at Khon Kaen University Hospital, Thailand. The inclusion criteria were adult patients who received either Xarator^® (original atorvastatin; Pfizer Pharmaceuticals, Puerto Rico) or Atorvastatin Sandoz^® (Lek Pharmaceuticals, Slovenia) for at least 3 months prior to switching therapy to the second brand: Lipostat^® (Siam Pharmaceutical, Thailand). The study period was between 1 April 2022 and 30 June 2023. The primary outcome of this study was a change in LDL 6 months after switching therapy from either the original (Xarator^®) or generic atorvastatin (Atorvastatin Sandoz^®).

Results: There were 683 patients who switched therapy from the original atorvastatin (Xarator^®), and 1044 patients who switched therapy from generic atorvastatin (Atorvastatin Sandoz^®), for a total of 1727 patients. Regarding LDL levels, switching therapy from original atorvastatin (Xarator^®) resulted in a slightly lower but not significant decrease in LDL at 6 months (- 0.96 mg/dL; 95% CI of - 3.20, 1.28), while switching therapy from generic atorvastatin (Atorvastatin Sandoz^®) led to significantly lower LDL at - 3.30 mg/dL (95% CI of - 5.25, - 1.36). The original (Xarator^®) and generic atorvastatin (Atorvastatin Sandoz^®) group also resulted in a significantly lower estimated glomerular filtration rate at - 0.90 and - 1.21 mL/min/1.73 m², respectively, from baseline.

Conclusions: The second generic atorvastatin (Lipostat^®) resulted in comparable outcomes on LDL compared with the original (Xarator^®), but significantly lower LDL levels than another generic atorvastatin (Atorvastatin Sandoz^®) 6 months after switching therapy. However, renal function should be closely monitored.

Background: In pulmonary arterial hypertension (PAH), comparative assessment of treatment effect on survival in randomized controlled settings of contemporary patients has not been feasible.

Objective: The aim of this study was to use EXPOSURE, the ongoing, real-world, post-authorization safety study, and commitment to the European Medicines Agency to perform pre-specified comparative survival analyses between patients that newly initiated selexipag versus other PAH-specific therapies by applying statistical methods to account for population differences.

Methods: EXPOSURE (EUPAS19085) is an observational study comprising patients with PAH who initiated selexipag or other PAH-specific therapy. To balance characteristics of patients in the other PAH therapy cohort with the selexipag cohort at PAH therapy initiation (baseline), propensity score weighting was applied. Mortality rate ratios (MRRs) were calculated.

Results: 2014 patients were available for analysis. Prior to applying propensity score weighting, patients in the selexipag cohort were more likely to have longer time from diagnosis, less functional impairment, and treatment with combination background therapy versus the other PAH therapy cohort. Following weighting, baseline variables for both cohorts were well balanced. Weighted treatment exposure was 827.9 and 840.5 person-years for the selexipag and modelled other PAH therapy cohort, respectively. Weighted proportion of deaths was lower in the selexipag versus modelled other PAH therapy cohort; MRR showed a higher survival rate for selexipag-treated patients (MRR [95% confidence interval]: 0.55 [0.31-0.99]).

Conclusions: Survival analyses in EXPOSURE suggest a reduced risk of mortality among the cohort of patients newly initiated on selexipag compared with the modelled cohort newly initiated with other PAH-specific therapies. Further research is needed to confirm this observation.

Trial registry: Trial registration: EUPAS19085.

Background: The humanized anti-disialoganglioside-2 monoclonal antibody naxitamab was approved in the USA in 2020 for the treatment of patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow, in combination with granulocyte-macrophage colony-stimulating factor. Treatment with naxitamab under expanded access was initiated by physicians from the Children's Hospital of Fudan University, Shanghai, China, in August 2021.

Objective: We reviewed all suspected adverse reactions (ARs) reported to the Y-mAbs Argus Global Pharmacovigilance Safety Database for patients treated with naxitamab under expanded access in China from 1 August 2021 to 31 July 2022.

Methods: We assessed patient demographics and the safety profile of naxitamab over multiple treatment cycles.

Results: At the data cutoff, 41 patients with relapsed/refractory high-risk neuroblastoma had received a total of 150 treatment cycles (451 infusions) of naxitamab. The median number of cycles completed was three; 13 patients (32%) were receiving ongoing naxitamab treatment. The median patient age was 3 years (range 1-9 years) and 63% were female. Overall, ARs were reported in 89/150 cycles (59%); serious ARs were reported in 23/150 cycles (15%). The cumulative reporting rate (ARs/cycle) decreased after 3 versus 12 months of expanded access: all ARs (8.7-4.6), serious ARs (0.9-0.3), hypotension (1.4-1.0), flushing (0.7-0.5), cough (0.6-0.3), pain (0.5-0.2), and hypoxia (0.3-0.2).

Conclusions: During the first 12 months of expanded access treatment in China, 41 patients received naxitamab therapy with a cumulative 451 infusions administered. Over the course of this expanded access program, a reduction in the AR rate, including serious ARs, was observed as more patients were initiated and proceeded to later treatment cycles. While additional research is needed, the observed decrease in the AR rate may be attributed to clinicians' increased knowledge of AR management and hands-on experience with naxitamab-treated patients.