Advances in Therapy最新文献

Introduction

The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA.

Methods

Data from IQVIA PharMetrics® Plus (January 1, 2016–June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance (“watch and wait” [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs.

Results

After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months–NR] vs 3.3 months [0.8 months–NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001).

Conclusions

Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice.

Introduction

SCT510 is a biosimilar to bevacizumab (Avastin) reference product (RP) that is approved for various metastatic cancers. In this study, we aimed to demonstrate the equivalence of SCT510 and bevacizumab in terms of efficacy, safety, immunogenicity and pharmacokinetics (PK) in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Methods

Patients with non-squamous NSCLC were randomized equally to the SCT510 group (comprising SCT510, paclitaxel, and carboplatin) and the bevacizumab group (comprising bevacizumab, paclitaxel, and carboplatin) for 4–6 cycles, followed by maintenance monotherapy with SCT510. The primary endpoint was the objective response rate (ORR) at week 12. Secondary endpoints included 18-week ORR, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and 1-year survival rate, as well as assessments of safety, immunogenicity, and multi-dose PK analysis.

Results

Between March 29, 2019, and April 27, 2021, 989 patients were screened and 567 eligible patients were randomly assigned to the SCT510 group (285 patients) and the bevacizumab group (282 patients). The ORR at week 12 was 52.6% [95% confidence interval (CI) 46.66–58.55%] in the SCT510 group and 52.5% (95% CI 46.47–58.47%) in the bevacizumab group. The ORR at week 18 was 55.4% (95% CI 49.46–61.30%) for SCT510 and 55.7% (95% CI 49.68–61.62%) for bevacizumab. The ORR risk ratio (RR) at weeks 12 and 18 was 0.99 (90% CI 0.873–1.133) and 0.99 (90% CI 0.872–1.114), respectively, both within the pre-specified equivalence margin of 0.75–1.33. There were no differences between the two groups in relation to other secondary endpoints, specifically DCR, DOR, PFS, OS, and 1-year survival rate. The overall safety findings were similar between the two treatment groups, and both SCT510 and bevacizumab RP exhibited low immunogenicity.

Conclusions

SCT510 is similar to bevacizumab in clinical efficacy, safety, immunogenicity, and PK in patients with advanced non-squamous NSCLC. The totality of the evidence supports the clinical equivalence of SCT510 and bevacizumab.

Trial Registration

NCT03792074.

Introduction

The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies.

Methods

A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation. Primary endpoint: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores).

Results

Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19–0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of − 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation.

Conclusion

Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

Introduction

Concomitant gallbladder and common bile duct (CBD) stones, known as cholecystocholedocholithiasis, are clinically prevalent. There is currently no consensus on sequential versus simultaneous management approaches, and, if simultaneous, which approach to adopt. This meta-analysis evaluates the safety and efficacy of one-stage laparoscopic cholecystectomy (LC) with intraoperative endoscopic retrograde cholangiopancreatography (ERCP) versus two-stage ERCP followed by LC for treating concomitant gallbladder and CBD stones.

Methods

A comprehensive literature search was conducted in five databases, PubMed, Embase, Web of Science, VIP, and Wanfang, for all randomized controlled trials (RCTs), cohort and retrospective studies published up to February 2024. Data extraction was performed independently by two reviewers. The primary outcomes were CBD stone clearance rate and postoperative complications morbidity. Secondary outcomes included conversion to other procedures and length of hospital stay. Statistical analyses were performed using R (v.4.3.2) with weighted mean differences and odds ratios (ORs) calculated for continuous and dichotomous variables, respectively, with 95% confidence intervals (CIs).

Results

A total of 17 studies involving 2120 patients have been included, with 898 patients receiving single-stage and 1222 patients undergoing two-stage treatment. Of these studies, 9 were RCTs and 8 were retrospective cohort study. The one-stage group demonstrated superior outcomes in terms of CBD stone clearance (OR = 2.07, p = 0.0004), overall morbidity (OR = 0.35, p < 0.0001), post-operative pancreatitis (OR = 0.49, p = 0.006), conversion to other procedures (OR = 0.38, p = 0.0006), and length of hospital stay (MD = – 2.6456, 95% CI – 3.5776; – 1.7136, p < 0.0001). No significant differences were observed in post-operative cholangitis (OR = 0.44, p = 0.12), post-operative bleeding (OR = 0.76, p = 0.47), or bile leakage (OR = 1.28, p = 0.54).

Conclusion

For patients with concomitant gallbladder and CBD stones, the one-stage approach combining ERCP and LC appears safer and more effective, with advantages including higher stone clearance rates, reduced postoperative complications (particularly pancreatitis), shorter hospital stays, fewer residual stones, and decreased need for additional procedures. However, additional high-quality clinical trials are needed to establish the optimal treatment approach for various patient scenarios.

Introduction

The aim of this observational, multicenter study was to assess the real-world use of brodalumab for the treatment of moderate-to-severe plaque psoriasis in patients in the Czech Republic, using data from the BIOREP registry.

Methods

The study included 273 patients aged ≥ 18 years with moderate-to-severe psoriasis who received brodalumab. Endpoints were drug survival (time from treatment initiation to discontinuation), effectiveness [Psoriasis Area and Severity Index (PASI)], and health-related quality-of-life [Dermatology Life Quality Index (DLQI)].

Results

Predicted drug survival probability was 92.4% [95% confidence interval (CI): 89.1, 95.7%] at 6 months and 84.2% (95% CI 79.5, 89.1%) at 12 months; this was maintained at 24 months [80.4% (95% CI 74.5, 86.8%)]. Younger age, higher body mass index, and no previous biologic treatment were significantly associated with longer drug survival. Absolute PASI ≤ 3 after 3 months was achieved by 89.8% of patients; 92.4%, 77.8%, and 59.1% reached PASI 75, PASI 90, and PASI 100, respectively. After 12 months, 96.5% of 141 patients had an absolute PASI ≤ 3. The proportion of patients achieving DLQI 0/1 was 87.3% at 12 months.

Conclusion

This study demonstrated high and sustained drug survival with high rates of skin clearance and improved quality of life in patients with relatively severe disease treated with brodalumab. Improvements were observed as early as 3 months post-treatment initiation and were sustained for up to 24 months in a real-life setting.

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

Introduction

Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study’s aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns.

Methods

A cross-sectional survey was conducted among US residents aged > 40 years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences.

Results

A total of 304 respondents completed the survey (mean age 64.4 years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65 years, while the Cost-sensitive group was mostly ≥ 65 years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost.

Conclusion

Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59–88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.

Introduction

Anemia is a common comorbidity of chronic kidney disease (CKD) that has been associated with increased risk of complications, healthcare expenditure, and reduced quality of life. In China, the treatment of anemia of CKD has been reported to be suboptimal in part because of a lack of awareness of the condition and its management. It is therefore important to raise awareness of the condition by estimating the future health and economic burden of anemia of CKD and also to understand how it may be addressed through proactive policies. This study aims to project the health and economic burden of anemia of CKD, in China, from 2023 to 2027 and to estimate the impact of a hypothetical intervention on related clinical and cost outcomes.

Methods

A virtual Chinese population was simulated using demographic, clinical, and economic statistics within a validated CKD microsimulation model. Each individual was assigned a CKD stage, anemia stage, comorbidity status (type 2 diabetes, hypertension), complication status (stroke, heart failure, and/or myocardial infarction), and a probability of receiving treatments and therapies. Annual direct healthcare costs were assigned and based on these factors. The hypothetical intervention reduced the prevalence of moderate and severe anemia by 5% annually. This hypothetical scenario was chosen to highlight the impact of implementing policies that could reduce anemia of CKD, and is aligned with the Healthy China 2030 policy, which aims to reduce mortality from noncommunicable diseases by 30%. Interventions could consist of early screening and intervention to reduce the escalation of anemia from mild to moderate or severe. Results were compared with a baseline “no change” scenario which reflects current trends.

Results

The number of patients with moderate/severe anemia of CKD was projected to increase from 3.0 to 3.2 million patients, with associated costs increasing from ¥22.0 billion (B) to ¥24.4B between 2023 and 2027, respectively. Compared with the no change scenario, the hypothetical intervention reduced the prevalence of moderate and severe anemia of CKD, saving ¥3.9B in healthcare costs in 2027 (¥24.4B vs ¥20.6B, respectively).

Conclusions

Consistent with trends in CKD burden in China, the prevalence of anemia of CKD is projected to increase, leading to greater related healthcare costs. The introduction of healthcare interventions designed to screen for and treat anemia more effectively could therefore reduce its future burden and related costs.

Early-stage (stage 1–3) chronic kidney disease (CKD) has an asymptomatic presentation such that most people with CKD are unaware of their disease status and remain undiagnosed. CKD is associated with multiple long-term conditions (MLTC), or multimorbidity, the most common of these being cardiovascular disease, hypertension, and type 2 diabetes. Primary care practitioners (PCPs) are crucial in the early identification and management of patients with CKD. For individuals at high risk of CKD, measurements of estimated glomerular filtration rate, urine albumin–creatinine ratio, and blood pressure should be obtained regularly and recorded in a timely manner. The importance of lifestyle changes in the prevention and management of CKD should also be highlighted. A recent addition to the treatment of CKD in people with and without type 2 diabetes has been the recommendation by clinical practice guidelines of a sodium–glucose co-transporter 2 (SGLT2) inhibitor alongside a renin–angiotensin–aldosterone system inhibitor as foundational therapy. SGLT2 inhibitors prevent CKD progression and reduce fatal and non-fatal kidney and cardiovascular events, hospitalization for heart failure, and all-cause mortality, and they have a favorable safety and tolerability profile. However, uptake has been slow, particularly in people with CKD without type 2 diabetes. A multifaceted approach is required to ensure that people with CKD receive optimal kidney protection. Measures to raise awareness of the importance of early identification and intervention include local/national campaigns via social media and practice-based education; clinical education programs; integration of clinical decision support tools into electronic health records; detection programs built around electronic health records; and good interdisciplinary communication. PCPs at the forefront of multidisciplinary care are best placed to implement the evidence-based clinical practice CKD guidelines for lifestyle modification and guideline-directed medical therapy.