BackgroundTolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We have investigated the cost-effectiveness of tolvaptan versus no active treatment (NAT) in adult patients within the licensed indication who have either failed to respond to fluid restriction or for whom the use of fluid restriction is not suitable, from the societal perspective in Sweden.MethodsA cost-utility analysis, considering a ‘general SIADH’ population and two subpopulations of patients (small-cell lung cancer [SCLC] and pneumonia) to broadly represent the complex clinical pathway of SIADH, was performed. A discrete event simulation was developed to model the progression of individuals through inpatient admissions over a 30-day time horizon (180 days for the SCLC cohort). Clinical data were derived from tolvaptan trials and observational data sources. All costs are given in Swedish kronor (SEK).ResultsIn the ‘general SIADH’ population, tolvaptan was associated with reduced costs (SEK 5,779 per patient [€624]) and increased quality-adjusted life-years (QALYs) (0.0019) compared with NAT and was therefore the dominant treatment strategy. Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients.ConclusionsTolvaptan represents a cost-effective treatment option in Sweden for hospitalised patients with HN secondary to SIADH who have either failed to respond to or are unsuitable for fluid restriction.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-016-0104-z) contains supplementary material, which is available to authorized users.

SummaryAimsHyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition.MethodsEmbase™, MEDLINE ®, MEDLINE ® In‐Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free‐text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions.ResultsThe searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full‐length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non‐RCTs, and 10 were case reports.DiscussionAlthough most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals.ConclusionThere is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.

This study showed that HN and/or SIADH negatively impact patient outcomes and healthcare resources related to hospital stay irrespective of the underlying cause. The impact of HN is not confined to the initial hospitalisation, as re-admission rates are also affected.

• Hyponatraemia is the electrolyte disturbance most commonly encountered in clinical practice (affecting 10-30% of hospitalised patients) and can be a marker of morbidity in many contexts, increasing mortality rates regardless of cause. 1• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hypotonic hyponatraemia, 2 responsible for approximately 30% of all patients with hyponatraemia.• Data from the US suggest that patients with hyponatraemia have a greater overall consumption of healthcare resources, and that hyponatraemia is associated with an increased length of hospital stay, [3][4][5] and increased direct medical costs. 6• The overall annual cost of hyponatraemia in the US alone has been estimated at $1.6-3.6 billion 7 -there are no comparable cost data for the UK.• The UK Consensus Statement recommends pharmacological therapy (demeclocycline or tolvaptan) for patients with mild/moderate hyponatraemia secondary to SIADH without severe symptoms, after fluid restriction has been attempted or deemed inappropriate. 8• The aim of this study was to understand how hyponatraemia secondary to SIADH is currently treated in England, and to understand the associated resource use.• A retrospective analysis of a patient cohort identified in IMS Hospital Treatment Insights (HTI) through hospital admission diagnosis codes from 1 January 2010 through to 31 October 2013 was conducted.• The HTI database, comprising details of all admissions and outpatient appointments to NHS hospitals in England, contains records on 3.3 million English patients from a source population of 13 million.• Adult patients were included if they had a new World Health Organization (WHO) ICD-10 diagnostic code for 'Hypo-osmolality and hyponatraemia' (E87.1) and/or a diagnostic code for SIADH (E22.2) during the study period.• Exclusion criteria were patients <18 years of age or with no age recorded, or co-morbid conditions associated with hyponatraemia: liver cirrhosis; liver disease with ascites; heart failure; unspecified adrenocortical insufficiency; hypothyroidism; and type 1 diabetes.• Study outcomes were captured through relevant WHO ICD-10 codes and comprised hospital admissions, outpatient visits, length of hospital stay, and in-hospital mortality.• In total, 37,425 patients were given a clinical code for SIADH or hyponatraemia ( Figure 1); >60% of patients were ≥68 years of age.• Of the patients with a diagnosis of hyponatraemia and/or SIADH, 1.8% were given demeclocycline, 0.3% were given tolvaptan, and 97.9% were not given any recorded pharmacological treatment. When pharmacological treatment was given, it was usually as monotherapy.• Mean time from diagnosis to initiation of therapy was similar for both demeclocycline and tolvaptan (10.2 days).-Median time was 3 days longer with tolvaptan at 8 days.• Patients receiving tolvaptan had a shorter mean (11.1 vs 19.3 days) and median (10 vs 14 days) length of hospital stay than those given demeclocycline.• Time to readmission and readmission rates at ...

0.377 QALYs (95% CI: -0.227 to 0.754) and cost savings of € 264 (95% CI: -€ 1,879 to € 2,768).. At a willingness-to-pay threshold of € 30,000 per QALY gained, SAXA strategy had an 82% probability to be cost-effective. Compared to TZD add-on to MET plus SU, the triple therapy with SAXA reached an incremental cost-effectiveness ratio of € 2,610 per QALY gained. ConClusions: Saxagliptin was predicted to be a cost-effective option in Spain when a new drug needs to be added in T2DM patients inadequately controlled with metformin and sulphonylurea alone. PDB105