Quantifying the benefits of early sublingual allergen immunotherapy tablet initiation in children.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airway, which progresses into allergic asthma (AA) in up to 45% of children. This analysis aimed to investigate clinical and economic benefits of sublingual allergen immunotherapy (SLIT tablets) initiated early in childhood for the treatment of AR by quantifying the long-term reduction in new cases of AA. METHODS: A Markov model was developed to estimate the long-term effects of SLIT tablets on the risk of developing asthma. Key parameters were primarily based on data from the GRAZAX® Asthma Prevention trial and included the age- and treatment-dependent risk of developing AA as well as annual probabilities of progression/remission in AR severity. Healthcare costs were estimated using data from the REACT study. RESULTS: In a modelled cohort of children with moderate-to-severe seasonal AR initiated on SLIT tablets at ages 7 and 12, 24% and 29%, respectively, develop AA during a 20-year period. In comparison, when initiated at age 5, 19% develop AA. Additionally, initiation of SLIT tablets at age 5 is associated with a total healthcare cost of EUR 20,429 per patient, whereas initiation at ages 7 and 12 is associated with, respectively, EUR 21,050 and EUR 22,379 per patient 20 years after AR diagnosis. CONCLUSION: Initiation of SLIT tablets in early childhood is associated with a clinically meaningful and permanent reduction in new cases of AA and lower healthcare costs among children with AR. This finding supports the clinical relevance of initiating SLIT tablets early for children with AR to obtain long-term clinical benefits.

Preferences for different treatment options among people living with acromegaly in the US.

OBJECTIVE: Acromegaly is a rare hormonal disorder that results in enlargement of the face, hands and feet. It is associated with comorbidities, increased mortality, reduced quality of life and economic burden. Adequate treatment is critical to alleviate symptoms; however, the treatment burden is substantial. To understand how different treatment aspects might ease the burden, this study investigated preferences for treatment options among people with acromegaly in the US, using a choice experiment (CE). METHODS: An online CE was conducted based on a similar study among the US general population. Respondents were recruited through Acromegaly Community in the US, and all eligible respondents were included. The survey assessed six treatment options that varied according to administration, frequency, storage, treatment setting, needle type and injection pain. RESULTS: 109 adults with acromegaly completed the survey between October and December 2022. On average, the population had lived with symptoms for 15 years, while the average number of years with the diagnosis was eight. Respondents preferred subcutaneous injections every fourth week and preferred them at home rather than at the hospital. Most respondents preferred subcutaneous injections right under the skin administered once every fourth week with a pen at home over oral capsules administered twice daily at home. CONCLUSION: The results indicate that new treatment options administered as subcutaneous injections right under the skin once every fourth week at home have the potential to lower the treatment burden among people with acromegaly, emphasizing the importance of taking each person's preference into consideration when choosing treatment.

Adherence and Persistence to Basal Insulin Among People with Type 2 Diabetes in Europe: A Systematic Literature Review and Meta-analysis.

INTRODUCTION: Diabetes is associated with a number of complications, particularly if glycaemic targets are not achieved. Glycaemic control is highly linked to treatment persistence and adherence. To understand the burden of poor persistence and adherence, this systematic literature review identified existing evidence regarding basal insulin adherence/non-adherence and persistence/non-persistence among people with diabetes in Western Europe (defined as the UK, France, Spain, Switzerland, the Netherlands, Ireland, Austria, Portugal, Denmark, Norway, Sweden, Finland, Italy, Germany, Iceland and Belgium). METHODS: Eligible studies were systematically identified from two databases, Medline and Embase (published between 2012 and June 2022). Conference abstracts from ISPOR and EASD were manually included. Identified studies were screened by two independent reviewers in a two-step blinded process. The eligibility of studies was decided on the basis of pre-established criteria. A proportional meta-analysis and comparative narrative analyses were conducted to analyse the included studies. RESULTS: Twelve studies were identified. Proportions of adherence/non-adherence and persistence/non-persistence varied across studies. Pooled rates of non-persistence at 6, 12 and 18 months were 20.3% (95% CI 13.8; 27.8), 33.8% (95% CI 24.1; 44.3) and 36.5% (95% CI 33.6; 39.4), respectively. In the literature, the proportion of adherent people ranged from 41% to 64% (using the outcome measure medication possession ratio (MPR) > 80%), with a pooled rate of 55.6% (95% CI 45.3; 65.6), suggesting that approximately 44% of people with type 2 diabetes (T2D) are non-adherent. CONCLUSION: The results highlight that almost half of patients with T2D in Western Europe have poor adherence to insulin therapy and, at 18 months, one in three patients do not persist on treatment. These findings call for new basal insulin therapies and diabetes management strategies that can improve treatment persistence and adherence among people with T2D.

Using risk-sharing agreements as a tool to promote the introduction of new, innovative medicine.

Risk-sharing agreements have been suggested as a tool to accelerate access to new innovative medicines by reducing risk for the stakeholders. Especially uncertainty in clinical effectiveness, safety and financial consequences for patients and buyers are aimed at being reduced. This article outlines the concept, a terminology and advantages and disadvantages of the agreements. We argue that all risk-sharing agreements involve both advantages and disadvantages among relevant stakeholders.

Population pharmacokinetics of piperacillin in plasma and subcutaneous tissue in patients on continuous renal replacement therapy.

OBJECTIVES: Piperacillin is a ß-lactam antimicrobial frequently used in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT). However, data regarding piperacillin tissue concentrations in this patient population are limited. A prospective observational study was conducted of free piperacillin concentrations during a single 8-h dosing interval in plasma (8 samples) and subcutaneous tissue (SCT) (13 samples), in 10 patients treated with CRRT following piperacillin 4 g given every 8 h as intermittent administration over 3 min. METHODS: A population pharmacokinetic model was developed using NONMEM 7.4.3, to simulate alternative administration modes and dosing regimens. SCT concentrations were obtained using microdialysis. Piperacillin concentrations were compared to the clinical breakpoint minimum inhibitory concentration (MIC) for Pseudomonas aeruginosa (16 mg/l), with evaluation of the following pharmacokinetic/pharmacodynamics targets: 50% fT > 1 × MIC, 100% fT > 1 × MIC, and 100% fT > 4 × MIC. RESULTS: SCT concentrations were generally lower than plasma concentrations. For the target of 50% free time (fT) > 1 × MIC and 100% fT > 1 × MIC, piperacillin 4 g every 8 h resulted in probability of target attainment (PTA) >90% in both plasma and SCT. PTA > 90% for the target of 100% fT > 4 × MIC was only achieved for continuous infusion. CONCLUSIONS: Piperacillin 4 g every 8 h is likely to provide sufficient exposure in both plasma and SCT to treat P.aeruginosa infections in critically ill patients on CRRT, given that targets of 50% fT > 1 × MIC or 100% fT > 1 × MIC are adequate. However, if a more aggressive target of 100% fT > 4 × MIC is adopted, continuous infusion is needed.