Matching-adjusted indirect comparison of adalimumab vs etanercept and infliximab for the treatment of psoriatic arthritis

Abstract

Objectives:

No head-to-head trial has compared the efficacy of adalimumab vs etanercept and infliximab for psoriatic arthritis (PsA). This study implements a matching-adjusted indirect comparison technique to address that gap.

Methods:

Patient-level data from a placebo-controlled trial of adalimumab (ADEPT) were re-weighted to match average baseline characteristics from pivotal published trials of etanercept and infliximab. ADEPT patients were re-weighted by odds of enrollment in comparator trials, estimated using logistic regression. Matched-on characteristics included PsA duration, age, gender, severity, active psoriasis, and concomitant treatment. After matching, placebo-adjusted treatment arms were compared at weeks 12 (or 14) and 24. Outcomes included ACR20/50/70, PsARC, HAQ, and modified TSS. PASI50/75/90 were compared for patients with active psoriasis. Cost per responder (CPR) was assessed in the US and Germany using matching-adjusted end-points and drug list prices. Statistical significance was assessed using weighted t-tests.

Results:

After matching, adalimumab-treated patients had greater placebo-adjusted rates of ACR70 and PASI50/75/90 at week 24 compared with etanercept (all p?<?0.05). Adalimumab patients had a higher placebo-adjusted rate of ACR70 than infliximab at week 14 (p?=?0.034). Adalimumab treatment had lower CPR for ACR70 and PASI50/75/90 compared with etanercept at week 24, in both the US and Germany (all p?<?0.02). Adalimumab had lower CPR than infliximab for all outcomes at week 24 (all p?<?0.05).

Conclusion:

Adalimumab is associated with higher ACR70 and PASI50/75/90 response rates than etanercept at week 24 and a higher ACR70 response rate than infliximab at week 14. Adalimumab has significant advantages over etanercept and infliximab in CPR across multiple end-points.

Key limitations:

The matching-adjusted indirect comparison method cannot account for unobserved differences in patient characteristics across trials, and only a head-to-head randomized clinical trial can fully avoid the limitations of indirect comparisons. CPR findings are limited to the US and German markets, and may not be generalizable to other markets with different relative pricing.     

National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans

Objective:

This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy.

Methods:

This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005–2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose?>?recommended label dose, (2) average ending dispensed dose?>?maintenance dose, and (3) average dose after maintenance dose?>?maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees.

Results:

Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p?p?p?Limitations:

Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ～50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations.

Conclusions:

In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.     

Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States

Abstract

Objective:

To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice.

Methods:

Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink? Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn’s disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included.

Results:

A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs.

Limitations:

This analysis is limited to three TNF-inhibitors and a US managed-care population.

Conclusions:

Based on this analysis of real-world use of TNF-inhibitors among patients in nationwide clinical practice settings, the annual TNF-inhibitor cost per treated patient was lowest for etanercept across all indications.     

基于TR的UWB微波肿瘤检测成像算法

时间反转(TR)技术的聚焦特性广泛应用于具有非均匀特性的组织检测中,基于TR的超宽带(UWB)微波检测成像算法是一种新型的高成像对比度及高成像分辨率的、对人体无损害、易于推广的检测技术。首先分析了该算法的可行性,然后深入研究了算法中肿瘤散射信号的提取方法,最后给出了仿真结果,证明该成像算法的有效性。     

Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective.

Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin’s lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).

Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively.

Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative.

Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.     

芒果苷对心肌缺血再灌注损伤TNF-a、MPO的影响

目的观察芒果苷对大鼠心肌缺血再灌注损伤（MI／R）TNF-α、MPO的影响。方法50只SD大鼠随机分为5组即假手术组、缺血再灌注模型组、芒果苷10mg/kg、20mg／kg、40mg／kg剂量组、假手术组给予等容量的生理盐水腹腔注射,完成模型全部操作只穿线不结扎。芒果苷10、20、40mg/kg剂量组分别给予相应剂量芒果苷腹腔注射21天,末次给药后一小时用于实验。采用左冠状动脉前降支结扎40min,再灌120min建立在体大鼠MIR模型。放免法检测心肌组织肿瘤坏死因子（TNF-α）含量;检测心肌组织髓过氧化酶（MPO）观察中性粒细胞（PMN）浸润、苏木素-伊红（HE）染色观察心肌组织病理改受,透射电镜观察心肌超微结构的改变。结果与模型组比较,芒果苷各剂量TNF-α和MPO含量显著降低（P〈0.01或P〈0．05）。结论芒果苷对MI／R有保护作用、芒果苷可减轻心肌细织中性粒细胞浸润,抑制炎症因子释放。     

Annual acquisition and administration cost of biologic response modifiers per patient with rheumatoid arthritis,psoriasis, psoriatic arthritis,or ankylosing spondylitis

Abstract

Objective:

To estimate annual biologic response modifier (BRM) cost per treated patient with rheumatoid arthritis, psoriasis, psoriatic arthritis, and/or ankylosing spondylitis receiving etanercept, abatacept, adalimumab, certolizumab, golimumab, infliximab, rituximab, or ustekinumab.

Methods:

This was a cohort study of 69,349 commercially insured individuals in a nationwide claims database with one of these conditions that had a claim for one of these BRMs between January 2008 and December 2010 (the index BRM/index date). Cost per treated patient was calculated as the total BRM acquisition and administration cost to the payer in the first year after the index date (including costs of other BRMs after switching) divided by the number of patients who received the index BRM. Etanercept was selected as the reference for comparisons.

Results:

Etanercept was the most commonly used index BRM (n?=?32,298; 47%), followed by adalimumab (n?=?20,582; 30%), infliximab (n?=?11,157; 16%), abatacept (n?=?2633; 4%), rituximab (n?=?1359; 2%), golimumab (n?=?687; <1%), ustekinumab (n?=?388; <1%), and certolizumab (n?=?245; <1%). Using etanercept as the reference, the cost per treated patient in the first year across all four conditions was 102% for adalimumab and 108% for infliximab. Newer BRMs had costs relative to etanercept that were 90% to 102% for rheumatoid arthritis, 132% for psoriasis, 100% for psoriatic arthritis, and 94% for ankylosing spondylitis.

Limitations:

Potential study limitations were the lack of clinical information (e.g., disease severity, treatment outcomes) or indirect costs, the inability to compare costs of newer BRMs across all four conditions, and much smaller sample sizes for newer BRMs.

Conclusions:

Of the BRMs that are approved for indications within all four conditions studied, etanercept had the lowest cost per treated patient when assessed across all four conditions.     

35例恶性肿瘤患者淋巴细胞Ag-NORs检测分析

目的细胞核仁形成区(NORs)由核糖体RNA基因组成,位于此区调控rRNA转录的酸性非组蛋白可被硝酸银染色(Ag-NOR),肿瘤细胞中Ag-NOR数目、分布和强度可作为肿瘤诊断、细胞分型和分化分级的重要指标。由于肿瘤细胞相关分子等的毒性作用,患者淋巴细胞NORs区的酸性非组蛋白得以表达。有别于非恶性疾病,并以此进行肿瘤诊断和病情监测。方法北京健尔康医疗设备有限公司提供的KL型肿瘤免疫图像分析系统,5%硝酸银及相应的银染试剂,RPMI1640培养液,普通细胞银染技术对患者外周血淋巴细胞染色。选择35例恶性肿瘤患者及35例健康对照者,经培养、制片、银染、图像分析四个步骤,计算T淋巴细胞核银染面积与细胞面积比值(即I.S%值)。结果对70例正常者和各种肿瘤患者的淋巴细胞酸性非组蛋白表达活性进行了对比研究,发现恶性疾病与正常者之间有明显差异。35例肿瘤患者中有28例阳性结果,有统计学意义,说明I.S%阳性结果与肿瘤有较密切联系,但并无特异性,这与有关文献报道相符。结论外周血T淋巴细胞Ag-NORs检测,可作为恶性肿瘤诊断及病情监测的重要参考指标。