Unmet needs in the management of immune-mediated thrombotic thrombocytopenic purpura and the potential role of caplacizumab in the UK-A modified-Delphi study.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare, blood-clotting disorder. Management historically relies on plasma exchange and immunosuppression; however, a 10%-20% mortality rate is still observed. Caplacizumab binds to von Willebrand factor and directly inhibits platelet aggregation; addition of caplacizumab to historical treatment induced faster resolution of platelet count in clinical trials. In 2019, a modified-Delphi study was conducted with UK experts, to develop consensus statements on management of acute TTP and the potential role of caplacizumab. An unmet need was acknowledged, and areas requiring improvement included: time to diagnosis and treatment initiation; time to platelet normalisation (TTPN) during which patients remain at risk of persistent microvascular thrombosis and organ damage; and incidence of subsequent exacerbations and relapses. Caplacizumab addition to historical treatment within 24 h (after confirmatory ADAMTS13 [a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13] assay) would significantly reduce TTPN, which directly influences acute outcomes, with manageable bleeding risk and reduced burden on healthcare systems. Expert panellists agree that poor outcomes in iTTP largely result from failure to rapidly control microvascular thrombosis. Use of caplacizumab during a confirmed iTTP episode could offer better control and may plausibly improve long-term outcomes. However, this consensus must be validated with further clinical trials and robust real-world evidence.

Correction to: The impact of perennial allergic rhinitis with/without allergic asthma on sleep, work and activity level.

[This corrects the article DOI: 10.1186/s13223-019-0391-9.].

The impact of perennial allergic rhinitis with/without allergic asthma on sleep, work and activity level.

Background: Allergic respiratory diseases such as allergic rhinitis (AR) and allergic asthma (AA) are common conditions that can influence sleep and daytime functioning. However, the significance of this impact is unclear-particularly in perennial allergy sufferers. This study investigates the impact of perennial allergy on sleep, daily activities and productivity. Methods: Adults with self-reported or physician-diagnosed perennial AR aged ≥ 18 years were recruited in Denmark, France, Germany and Sweden. Allergy sufferers were identified using online panels closely matching national population characteristics for each country. Impact on sleep, work, productivity and activity (by the Work, Productivity and Activity Index) were analysed. Descriptive analyses were conducted. Results: In total, 511 subjects with perennial AR (47.4% also with seasonal allergy) completed the survey. Most subjects (77.5%) had a physician-diagnosis of AR; 46.4% were diagnosed with both AA and AR. Most subjects (65.2%) reported sensitisation to house dust mites. Of all subjects, 66.0% reported sleep problems. Subjects with sleep problems woke, on average, 3.8 times per night, with 92.0% taking 15+ min to fall asleep (22.2% took 60+ min). Upon waking at night, 40.8% struggled to get back to sleep, and 69.2% had difficulties waking in the morning due to tiredness. Disturbances in daily functioning due to sleep issues were reported in 85.5-95.0% of subjects with sleep problems across all aspects investigated. Overall work and activity impairment were 53.3% and 47.1%, respectively. Sleep issues were more frequent (78.1% vs 54.7%) in those diagnosed with both AR and AA compared to AR alone, and more burdensome, with a greater impact on daily functioning (47.0% vs 33.3%) and impairment in work and activity (62.0% and 54.9% vs 39.3% and 35.2%, respectively). Of all subjects, 20.5% were receiving AIT at the time of the survey; of these, 36.4% reported moderate or great improvement in sleep due to allergy treatment. Conclusions: In perennial AR sufferers, sleep problems are common and impact on daily functioning, with results indicating a greater burden in those with both AR and AA compared to AR alone.

Critical inhaler errors in asthma and COPD: a systematic review of impact on health outcomes.

BACKGROUND: Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment. METHODS: A systematic review was conducted to define 'critical' errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2). RESULTS: Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2 identified 9 studies. We observed 299 descriptions of critical error. Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency. A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden. CONCLUSIONS: We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes. Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.

Adherence to topical therapies in actinic keratosis: A literature review.

BACKGROUND: Actinic keratosis (AK) is a common skin condition, for which topical therapies are frequently prescribed. This review summarises current understanding of patient adherence and persistence to topical AK treatment by identifying literature relating to measures of adherence and persistence and influencing factors. METHODS: A multi-database literature search was conducted (2004-2015) using key search terms. Supplementary searches of pivotal clinical trials and reference lists of eligible papers were also conducted. RESULTS: Non-adherence and non-persistence rates varied between real-world studies (10-63% and 23-31%, respectively), with combined non-adherence and non-persistence reported as high as 88%. Methods to calculate adherence and persistence differed between studies. Adherence and persistence were generally higher in clinical trials than clinical practice. Key contributing factors to non-adherence and non-persistence to AK treatment were identified as: treatment duration, severity and persistence of local skin responses and patient confusion over treatment regimens. CONCLUSION: The review highlighted a significant evidence gap regarding adherence and persistence to topical AK therapies. Combined, non-adherence and non-persistence may be as high as 88% in clinical practice, highlighting the importance of incorporating contributing factors to patient non-adherence into treatment decisions.

FP/FORM Versus FP/SAL Within Clinical Practice: An Updated Budget Impact Analysis in Asthma.

INTRODUCTION: Pressurized metered-dose inhalers (pMDI) such as fluticasone propionate and salmeterol (FP/SAL) are commonly used for the treatment of asthma in the UK. Previously, a budget impact analysis demonstrated that use of FP and formoterol fumarate (FP/FORM) pMDI as an alternative to FP/SAL pMDI, would be a cost-saving option for the UK National Health Service (NHS). This budget impact analysis aimed to update the existing analysis with prescription volume data and real-world evidence since the introduction of FP/FORM to the UK market. METHODS: Patient Data (IMS Information Solutions UK Ltd) moving annual total (MAT) August 2015 were used to ascertain the number of units of pMDI prescribed. Annual costs to the NHS in terms of drug, administration, monitoring and adverse event costs, were used to estimate the potential budget impact for FP/FORM and FP/SAL. Costs were calculated for current prescription volumes (12% FP/FORM, 88% FP/SAL), and for different prescription volume scenarios (FP/FORM at 0%, 25%, 50% and 100%). Real-world evidence and budget impact at a clinical commissioning group (CCG) level were also considered. RESULTS: Total annual costs per person year were less with FP/FORM (£625) than with FP/SAL (£734). Annual costs to the NHS based on the current prescription volumes and clinical trial data were estimated at £210.0M, however, based on real-world evidence, costs were estimated at £179.8M. For all scenarios with increased FP/FORM prescription volumes, the annual total costs to the NHS decreased. This was reflected at a CCG level. CONCLUSION: The use of FP/FORM as an alternative to FP/SAL can result in cost savings for the NHS when assessing drug, administration, monitoring and adverse events costs. The inclusion of data released since the launch of FP/FORM within the budget impact analysis demonstrates that the potential cost savings to the NHS that were previously published are being translated to clinical practice. FUNDING: Mundipharma, UK.