Dose-escalation of adalimumab, golimumab or ustekinumab in inflammatory bowel diseases: characterization and implications in real-life clinical practice.

OBJECTIVES: Dose-escalation is a common practice to optimize treatment with subcutaneously administered biologicals in Crohn's disease (CD) and ulcerative colitis (UC). However, limited data is available on the extent of dose-escalation in real-life. Here, we analyzed treatment persistence, dose-escalation, concomitant corticosteroid use, and costs of adalimumab, golimumab, and ustekinumab in inflammatory bowel diseases (IBD). METHODS: This was a nationwide, retrospective, non-interventional registry study. All adult patients who were diagnosed with CD or UC and had purchased adalimumab, golimumab, or ustekinumab from Finnish pharmacies between 2008 and 2018 were included in the study and followed up for 24 months after treatment initiation. RESULTS: A total of 2884 patients were included in the analyses. For adalimumab, treatment persistence was higher for CD patients compared to UC patients both at months 12 (46.2% versus 37.1%; p < .0001) and 24 (26.1% versus 19.7%; p < 0.0001). For golimumab (UC), treatment persistence was 48.3% at month 12 and 28.1% at month 24. The 12-month treatment persistence rate for patients on ustekinumab (CD) was 47.1%. Cumulative doses exceeding the regular dosing according to the summary of product characteristics (SPC), was observed for adalimumab in CD during the first 6 months of treatment (62.9% of the treatment periods), golimumab in the later stages of the UC treatment (52-54% of treatment periods at months 7-24), and ustekinumab during the first 6 months (70.7%). CONCLUSIONS: Based on this study, dose-escalation of subcutaneously administered biologicals is a common clinical practice in IBD. This has implications for treatment costs, use of concomitant medications, and treatment outcomes.

Healthcare resource utilization and treatment costs of Finnish chronic inflammatory bowel disease patients treated with infliximab.

Objectives: Inflammatory bowel disease (IBD) is associated with a high economic burden to society due to its early onset and chronic character. Here, we set out to characterize healthcare resource utilization and associated costs in Crohn's disease (CD) and ulcerative colitis (UC) patients with infliximab treatment, the most widely used first-line biologic agent in Finland, in a real-world clinical setting. Methods: This was a retrospective, non-interventional single-center study. Infliximab was administered in routine care, and data were collected retrospectively from electronic health records. All adult anti-TNF naïve CD or UC patients whose infliximab treatment was initiated at the Hospital District of Southwest Finland between the years of 2014 and 2016 were included in the study. Each patient was followed-up for 12 months after the initiation of infliximab treatment. Results: A total of 155 patients were included (45 CD, 110 UC). Altogether, 60.0% (n = 27) of all CD patients and 43.6% (n = 48) of all UC patients persisted on infliximab therapy 12 months after treatment initiation. The total cost was similar for both CD and UC cohorts (CD, €10,243; UC, €10,770), infliximab treatment being the highest individual cost (60.3% of the total cost in CD; 53.4% in UC). The mean number of infliximab infusions during the 12-month follow-up was 7.0 for CD and 6.5 for UC patients. Conclusions: IBD causes a significant burden to the Finnish healthcare system. This study provides a detailed characterization of the cost landscape of IBD and contributes to optimizing treatment strategies and healthcare resource use in the biosimilar era.

Characterization of inflammatory bowel disease management by vedolizumab and concomitant treatments in real-life clinical practice.

Limited data is available on vedolizumab combination therapies in real-world clinical practice. Here, we evaluated the concomitant corticosteroid, immunosuppressive, and 5-aminosalicylic acid utilization of inflammatory bowel disease (IBD) patients treated with vedolizumab in a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centres with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) who had at least one vedolizumab infusion since it's availability in Finland were included in the study. Data were collected from medical charts at baseline (vedolizumab treatment initiation), week 14, and month 6. The majority of patients who used corticosteroids at the baseline and persisted on vedolizumab treatment for 6 months were taken off corticosteroid treatment by the 6-month time point (CD, 54.5%; UC, 69.8%). Modest corticosteroid dose reductions were observed among treatment persistent CD patients from the baseline until month 6. Corticosteroid users had less vedolizumab discontinuations due to primary ineffectiveness and more discontinuations due to adverse events than patients not using corticosteroids. Vedolizumab may have a corticosteroid sparing effect in real-world clinical practice. Concomitant corticosteroid use may lead to a lower rate of vedolizumab discontinuation due to primary ineffectiveness, but a higher discontinuation rate due to adverse events.

Patient preferences for dry powder inhaler attributes in asthma and chronic obstructive pulmonary disease in France: a discrete choice experiment.

BACKGROUND: Dry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies. Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients' preferences for different attributes of DPIs. METHODS: Attributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study). An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase). A fractional factorial design including three blocks of 12 choice sets was created. Each choice set comprised three alternatives: two fictitious inhalers and the patient's current inhaler. Marginal utilities were estimated using a ranked ordered logit model. Interactions between attributes and disease (asthma or COPD) were tested. RESULTS: Six DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties. Overall, 201 patients with asthma and 93 with COPD were included in the online survey. Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77-€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95-€6.02]). Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65-€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98-€ 7.77]). CONCLUSION: This study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.

Costs in different states of prostate cancer.

OBJECTIVES: This cross-sectional study assesses resource use and costs in different states of prostate cancer (PCa) in a real-life setting. Costs were estimated as incremental costs due to cancer for a six-month period and they included direct medical costs, productivity costs and costs of informal care. METHODS: Resource use and cost data, irrespective of who the payer was, were retrieved from the registries for 611 PCa patients in the Helsinki area in Finland. In addition, patients answered background questions concerning informal care, work capacity and educational status. Patients were divided into four mutually exclusive groups based on disease state and time from diagnosis: primary (local disease, first six months after diagnosis; n = 47), rehabilitation (local disease, 0.5-1.5 years after diagnosis or recurrence; n = 158), remission (local disease, more than 1.5 years after diagnosis; n = 317) and metastatic (after detection of metastases; n = 89). RESULTS: Costs differed markedly between the states of disease. Mean direct health care costs for the six-month periods were: primary treatment state € 2750, rehabilitation state € 1143, remission state € 760 and metastatic state € 7423. Productivity costs were also highest (€ 4277) in the metastatic state. Overall, the average share of indirect costs was around one third of the total costs. However, when including informal care, their combined share of the total costs increased to around half or more. CONCLUSIONS: The results provided state-specific estimates of the direct health care and indirect costs of PCa in Finland. The treatment of metastatic disease is significantly more costly than treatment of early stage PCa. Although direct medical costs were higher compared to productivity costs, they should be taken into consideration when evaluating the costs of PCa.

USE OF PATIENT ASSESSED HEALTH-RELATED QUALITY OF LIFE INSTRUMENTS IN PROSTATE CANCER RESEARCH: A SYSTEMATIC REVIEW OF THE LITERATURE 2002-15.

OBJECTIVES: The objectives of this study were to identify and qualitatively describe, in a systematic literature review, published studies that collected prostate cancer patients' health-related quality of life (HRQoL) estimates by using validated, generic instruments. METHODS: Systematic searches of the literature were made using the Medline, Cochrane Library, PsycINFO, and CINAHL electronic databases from 2002 to 2015. RESULTS: The search identified 2,171 references, of which 237 were obtained for full-text assessment; thirty-three of these articles were deemed relevant and included in the systematic review. An indirect valuation method was used in 73 percent (n = 24) of the studies. The most commonly used HRQoL instrument with an indirect valuation method was the EuroQol (EQ-5D; n = 21), and the second most common was the 15D (n = 5). A direct valuation method was used in 48 percent (n = 16) of the studies. Of these, the Visual Analogue Scale (VAS) was the most often used (n = 10), followed by the Time-Trade-Off (n = 6). HRQoL scores varied in localized and early stage disease between 0.63 and 0.91, and in advanced or metastatic disease stage between 0.50 and 0.87. There was also variance in the HRQoL instruments and study methods used, which explains the large variance in HRQoL scores between the various disease stages. CONCLUSIONS: Although utility and quality-adjusted life-years gained are considered important measures of effectiveness in health care, the number of studies in which utilities of prostate cancer patients have been estimated using generic HRQoL instruments, based on either direct or indirect measurement of HRQoL, is fairly small.

Costs of colorectal cancer in different states of the disease.

OBJECTIVES: This cross-sectional study estimates the resource use and costs among prevalent colorectal cancer (CRC) patients in different states of the disease. METHODS: Altogether 508 Finnish CRC patients (aged 26-96; colon cancer 56%; female 47%) answered a questionnaire enquiring about informal care, work capacity, and demographic factors. Furthermore, data on direct medical resource use and productivity costs were obtained from registries. Patients were divided into five mutually exclusive groups based on the disease state and the time from diagnosis: primary treatments (the first six months after the diagnosis), rehabilitation, remission, metastatic disease, and palliative care. The costs were calculated for a six-month period. Multivariate modeling was performed to find the cost drivers. RESULTS: The costs were highest during the primary treatment state and the advanced disease states. The total costs for the cross-sectional six-month period were €22 200 in the primary treatment state, €2106 in the rehabilitation state, €2812 in the remission state, €20 540 in the metastatic state, and €21 146 in the palliative state. Most of the costs were direct medical costs. The informal care cost was highest per patient in the palliative care state, amounting to 33% of the total costs. The productivity costs varied between disease states, constituting 19-40% of the total costs, and were highest in the primary treatment state. CONCLUSIONS: The first six months after the diagnosis of CRC are resource intensive, but compared with the metastatic disease state, which lasts on average for 2-3 years, the costs are rather modest. Informal care constitutes a remarkable share of the total costs, especially in the palliative state. These results form a basis for the evaluation of the cost effectiveness of new treatments when allocating resources in CRC treatment.

Health-related quality of life among breast, prostate, and colorectal cancer patients with end-stage disease.

PURPOSE: To explore end-stage breast, prostate, and colorectal cancer patients' health-related quality of life (HRQoL); to compare results obtained by different HRQoL instruments; and to explore factors related to impaired HRQoL. METHODS: A cross-sectional observational study utilized two generic HRQoL instruments, the 15D and the EQ-5D, and a cancer-specific instrument, the EORTC QLQ-C30. Patients were recruited from the Helsinki University Hospital's Department of Oncology and from a local hospice. RESULTS: Of the 114 palliative care patients included in the analysis, 27 had breast cancer, 30 had prostate cancer, and 57 had colorectal cancer. Of these, 28 % died within 3 months after their response, while 32 % died within three to 6 months, and 39 % died more than 6 months after. Utility values varied widely by instrument: the 15D gave the highest utility values and VAS the lowest (15D: 0.74, EQ-5D: 0.59 and VAS: 55). Patients close to death had lower HRQoL scores independently from the instrument used. The EQ-5D showed a pronounced ceiling effect, with 13 % of patients reporting full health, whereas the corresponding figures for the 15D and VAS were 1 and 0 %, respectively. Fatigue was the most common symptom and also predicted impaired HRQoL most significantly. CONCLUSIONS: All instruments were applicable for the evaluation of HRQoL among end-stage cancer patients. Fatigue seemed to be the most significant deteriorating factor, whereas clinical and demographic factors had less of an effect on HRQoL.

Health-related quality of life in prostate cancer.

BACKGROUND: With new treatment options, the prognosis of prostate cancer (PCa) has improved in recent decades, and health-related quality of life (HRQoL) has become an important outcome of treatment. HRQoL scores are also essential for health economic analyses concerning treatment options for the disease. This study assesses HRQoL scores in different health states of PCa, compares the results obtained by different HRQoL instruments, compares the HRQoL of PCa patients with that of the general population, and explores factors associated with the resultant HRQoL scores. MATERIAL AND METHODS: An observational cross-sectional study among PCa patients in the Helsinki and Uusimaa Hospital District between September 2009 and December 2010. A total of 630 PCa patients (aged 43-92) assessed their HRQoL with the generic 15D and EQ-5D, as well as the cancer-specific EORTC QLQ-C30 questionnaires. Patients were divided into five mutually exclusive groups based on disease state: Loc1 (local disease, first six months after diagnosis; n = 47), Loc2 (local disease, 0.5-1.5 years after diagnosis or recurrence; n = 158), Loc3 (local disease, more than 1.5 years after diagnosis; n = 317), Metastatic (after detection of metastases; n = 89) and Palliative care (n = 19). Multivariate analysis served to evaluate the factors associated with the HRQoL scores. RESULTS: The utility scores were highest at baseline. Markedly impaired HRQoL was seen first at the more advanced states of the disease. All HRQoL instruments studied were consistent in all states of the disease, yet the HRQoL scores obtained varied widely. Symptoms of fatigue and pain, and background variables of financial difficulties and age were the most important factors associated with poor HRQoL. CONCLUSIONS: All instruments provided valuable insight into PCa patients' overall HRQoL. Management of cancer-related symptoms is important in maintaining patients' HRQoL, but more attention should also focus on financial difficulties.

Impact of HPV16/18 vaccination on quality of life: a pilot study.

OBJECTIVES: Genital human papillomavirus (HPV) infections and associated precancerous lesions adversely affect health-related quality of life (HRQoL). HPV vaccines provide effective protection against these conditions. We therefore investigated the impact of HPV vaccination on HRQoL in young women five years after participation in a phase III HPV vaccination trial. METHODS: A total of 4808 originally 16- to 17-year-old Finnish girls had participated in the PATRICIA trial and received either bivalent HPV 16/18 vaccine or hepatitis A-virus (HAV) vaccine in 2004 to 2005. Unvaccinated girls (n = 9602), from adjacent birth cohorts, had participated in the control cohort in 2005. From 2009 to 2011, at 22 to 23 years of age, all participants received a questionnaire consisting of two generic HRQoL instruments (RAND36 and EQ VAS) and a disease-specific questionnaire (CECA10). RESULTS: We analysed responses of 1143 HPV 16/18-vaccinated, 980 HAV-vaccinated, and 3753 unvaccinated young women. The unadjusted mean outcome measures of the different HRQoL estimates were similar in the three different responder cohorts. CONCLUSIONS: Five years after vaccination the health-related quality of life of HPV 16/ 18- vaccinated young women did not differ from those of HAV-vaccinated or unvaccinated controls representing the general population.

Regulation Awareness and Experience of Additional Monitoring among Healthcare Professionals in Finland.

BACKGROUND: Challenges in post-marketing adverse event reporting are generally recognized. To enhance reporting, the concept of additional monitoring was introduced in 2012. Additional monitoring aims to enhance reporting of adverse events (AE) for medicines for which the clinical evidence base is less well developed. PURPOSE: The purpose was to get a deeper understanding of the underlying reasons why additional monitoring has not increased AE reporting as much as initially hoped. We examined how healthcare professionals (HCPs) in Finland perceive additional monitoring, why they do or do not report AEs more readily for these medicines and how they interact with patients treated with additionally monitored medicines. METHODS: An anonymous, open questionnaire was developed and made available online at the e-form portal of University of Helsinki. Physicians, nurses, and pharmacists were invited to complete the questionnaire via their respective trade or area unions. Content analysis of answers to open-ended questions was performed by two independent coders. RESULTS: Pharmacists have the best understanding about additional monitoring but at the same time do not recognize their role in enhancing monitoring. Only 40% of HCPs working with patients knows always or often if a specific medicine is additionally monitored. Half (53%) of HCPs do not tell or tell only rarely patients about additional monitoring. 18% of HCPs reported having received additional monitoring training whereas 29% had received general AE reporting training. AE reporting was more common among HCPs who had received training. CONCLUSIONS: Additional monitoring awareness among HCPs and patients should be increased by organizing regular educational events and making additional monitoring more visible. Educational events should emphasize the significance additional monitoring has on patient safety and promote a reporting culture among HCPs.

Costs of administration, travelling, and productivity losses associated with hospital administration of multiple myeloma drugs in Finland.

AIM: To estimate the drug administration, travelling, and productivity costs associated with infusion or subcutaneous proteasome inhibitor (PI) treatments (specifically carfilzomib and bortezomib) for multiple myeloma (MM) patients in Finland. MATERIALS AND METHODS: Price tariffs of Finnish hospital districts are used as the basis of invoicing sent to healthcare service payers. A review of these price tariff lists was conducted and obtained data analysed to estimate the mean unit cost of PI administration visit. Travelling costs stratified by areas with different population densities were assessed, based on the national travelling reimbursement register data maintained by the Social Insurance Institution of Finland. Productivity costs due to time spent on administration visits and travelling were estimated based on an expert interview and a spatial healthcare accessibility analysis. RESULTS: Nineteen (95%) of the Finnish hospital districts were included in the review. Relevant unit cost information was found for 15 (75%) of the districts. The mean PI administration cost alone was 270€ (95% CI = 189€-351€) per administration and increased to 371€ when travelling costs were included. Productivity costs added, the mean PI administration costs totalled 405€ for bortezomib and 437€ for carfilzomib. LIMITATIONS: The costing rationale of price tariffs may vary between hospital districts. Productivity costs were estimated conservatively, due to lack of data. CONCLUSIONS: The administration of intravenous or subcutaneous PIs to treat MM in healthcare facilities causes significant and potentially avoidable healthcare, travelling, and indirect costs, and they should be included in all health economic evaluations (HEEs). As the cost estimates utilized in this study represent most of central hospitals in the country, they provide useful information for future HEEs. A broader conclusion is that novel oral medications, such as the first oral PI, have a significant potential for reducing administration-related costs of subcutaneous or intravenous PIs.

Misuse and/or treatment delivery failure of inhalers among patients with asthma or COPD: A review and recommendations for the conduct of future research.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are widespread chronic conditions with medication frequently delivered by inhalers. These can be challenging to use correctly, but the scale of misuse and the specific aspects of failure are unclear. METHODS: We used systematic review methods to search 9 databases in May 2015 to identify and review studies that assessed adults (18 years or older) with asthma or COPD using inhalers of various types including pressurised metered dose inhalers (pMDIs), dry powder inhalers and the Respimat inhaler. Studies must have reported the scale of inhaler misuse, variation by type of inhaler or which steps patients had difficulty completing accurately. RESULTS: The types of inhalers, inhaler interventions and definitions of failure and misuse varied widely in the 38 studies identified. It was not possible to draw conclusions on the differential failure rates between different types of inhalers or any patient characteristics. Of the studies reporting failure or misuse rates, the majority ranged between 0 and 20%. Studies were inconsistent regarding the number of inhaler steps collected, reported and labelled as critical. CONCLUSIONS: There is evidence for all identified inhalers that some people may be using them incorrectly, but it is unclear which inhalers have higher rates of misuse or which steps within the inhaler technique are most difficult for patients. The optimal techniques for using inhalers are not standardised. Researchers undertaking future inhaler studies are respectfully directed to our recommendations for future research.

Health-related quality of life among prostate cancer patients: real-life situation at the beginning of treatment.

OBJECTIVE: The aims of this study were to measure the real-life health-related quality of life (HRQoL) of newly diagnosed prostate cancer (PCa) patients, to compare it with that of the general male population and to explore factors affecting HRQoL. METHODS: All newly diagnosed PCa patients in the Helsinki University Hospital were asked to fill in 15D and EORTC QLQ-C30 questionnaires. Clinical background information was collected retrospectively from patient charts. Patients were categorized into three mutually exclusive groups based on the disease stage: Local, Locally advanced and Metastatic groups. Multivariate linear regression analysis was conducted to explore which factors explained variance in 15D scores. A regression model was built to map the EORTC QLQ-C30 to 15D in a random sample of 50% of patients and the model was tested in the other half of the patients. RESULTS: In total, 1050 men with a mean age of 67 years responded to the questionnaires. The mean ± SD 15D score of patients was slightly lower than that of the age-standardized general male population: 0.905 ± 0.089 vs 0.915 ± 0.082 (p = .057). The mean ± SD 15D utility scores were 0.912 ± 0.084, 0.897 ± 0.102 and 0.855 ± 0.109 for Local, Locally advanced and Metastatic groups, respectively. The mapping model of EORTC QLQ-C30 to 15D was robust and fitted well (root mean square error = 0.042, adjusted R² = .79). CONCLUSIONS: The HRQoL of PCa patients entering treatment was similar to that of the general population. HRQoL was most impaired among patients with metastatic disease, whereas the difference between patients with localized PCa and the general population was minor. Mapping indicated that the 15D score aggregates quite accurately the information from the EORTC QLQ-C30.

Evaluation of inhaler handling-errors, inhaler perception and preference with Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: a single site, single visit crossover study (Finhaler).

INTRODUCTION: Correct inhaler technique and device preference are positively correlated with improved adherence and clinical outcomes. This study was designed to investigate inhaler technique mastery and device preference for three different dry powder inhalers, Spiromax, Easyhaler and Turbuhaler. METHODS: This was a single site, single visit, crossover study assessing device mastery, handling errors and preference using empty Spiromax, Easyhaler and Turbuhaler devices in healthy adult Finnish volunteers. Inhaler naïve adult participants were observed by healthcare professionals (HCPs) to evaluate the proportion of participants achieving device mastery (defined as an absence of HCP observed errors) using a three-step approach: (1) intuitive use (with no instructions), (2) after reading the patient information leaflet and (3) after HCP instruction. HCPs monitored and recorded errors based on device-specific handling error checklists. At the end of the study, participants completed a device preference questionnaire and rated their satisfaction with the three devices. RESULTS: Spiromax was correctly used by 37.5% and 93.3% of participants in steps 1 and 2, respectively, compared with 0% and 58.3% with Easyhaler, and 9.2% and 76.7% with Turbuhaler. All three devices showed high mastery (>95%) in step 3. The most common error reported with Spiromax was related to the orientation of the device. Not shaking the device was the most common error with Easyhaler. Errors in priming the device were the most common with Turbuhaler. Spiromax, Easyhaler and Turbuhaler were rated as the 'easiest device to use' by 73.1%, 12.6% and 14.3% of participants, respectively. The HCP instructions clearly improved the use of all devices. CONCLUSION: Higher levels of device mastery, including intuitive/ease of use, were reported by naïve users when using Spiromax compared with Easyhaler and Turbuhaler.

Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance.

OBJECTIVE: To identify the impact of delivery device of inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA) on asthma medication compliance, and investigate other factors associated with compliance. MATERIALS AND METHODS: We conducted a retrospective and multicenter study based on a review of medical registries of asthmatic patients treated with ICS/LABA combinations (n=2,213) whose medical devices were either dry powder inhalers (DPIs, such as Accuhaler(®), Turbuhaler(®), and NEXThaler(®)) or pressurized metered-dose inhalers (pMDI). Medication compliance included persistence outcomes through 18 months and medication possession ratios. Data on potential confounders of treatment compliance such as asthma exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also explored. RESULTS: The probability of asthma medication compliance in case of DPIs was lower compared to pMDIs, which suggests that inhaler devices influence inhalation therapies. There were additional confounding factors that were considered as explanatory variables of compliance. A worse measure of airflow obstruction (forced expiration volume in 1 second), comorbidities and general practitioner (GP) consultations more than once per month decreased the probability of compliance. Within comorbidities, alcoholism was positively associated with compliance. Patients of 29-39, 40-50, and 51-61 age groups or suffering from more than two exacerbations during the study period were more likely to comply with their medication regime. The effects of DPIs toward compliance varied with the different DPIs. For instance, Accuhaler(®) had a greater negative effect on compliance compared to Turbuhaler(®) and Nexthaler(®) in cases of patients who suffered exacerbations. We found that GP consultations reduced the probability of medication compliance for patients treated with formoterol/budesonide combination. For retired patients, visiting the GP increased the probability of medication compliance. CONCLUSION: We concluded that inhaler devices influence patients' compliance for long-term asthma medication. The impact of Accuhaler(®), Turbuhaler(®), and NEXThaler(®) on medication compliance was negative. We also identified some confounders of medication compliance such as patient's age, severity of asthma, comorbidities, and health care costs.

The importance of inhaler devices: the choice of inhaler device may lead to suboptimal adherence in COPD patients.

OBJECTIVE: This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC) of inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA), focusing on the importance of inhaler devices. METHODS: We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263) treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDI). Medication adherence included persistence outcomes through 18 months and medication possession ratios. Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence. RESULTS: The analyses revealed that COPD patients whose medication was delivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients. Younger groups of patients were less likely to be adherent compared to the oldest group. Smoker men were less likely to be adherent compared to women and non-smokers. Comorbidities decreased the probability of treatment adherence. Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor. We also found that worsening of COPD is negatively associated with adherence. CONCLUSION: According to this study, inhaler devices influence patients' adherence to long-term COPD medication. We also found that DPIs delivering ICS/LABA FDC had a negative impact on adherence. Patients' clinic and socioeconomic characteristics were associated with adherence.

Expert Nordic perspectives on the potential of novel inhalers to overcome unmet needs in the management of obstructive lung disease.

The effective self-management of obstructive lung disease is dependent upon the patient achieving good inhaler technique. However, many current inhalers are complicated to use, which may lead to handling difficulties. These difficulties can cause clinically relevant errors, whereby pharmacotherapy fails to achieve adequate lung deposition and therapeutic effect. In this report, the potential of novel inhaler devices to overcome unmet needs in the management of obstructive lung disease is considered by a panel of Nordic experts. The panel concludes that innovative inhalers can contribute to good disease management and better use of healthcare resources.

A review of the value of innovation in inhalers for COPD and asthma.

BACKGROUND: Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. METHODS: In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. CONCLUSIONS: The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms.

Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise.

OBJECTIVES: the study aims to estimate the clinical-impact and cost-effectiveness value of adding human papillomavirus 16/18 vaccination against cervical cancer among women currently undergoing organised screening in Finland. METHODS: A Markov cohort model evaluating high-risk HPV infections and cervical cancer (CC) cases combined with screening has been customised to the Finnish setting. The model outcome for a cohort of 30,000 girls aged 10 years was calibrated to age-specific annual number of Pap smears, CC incidence and mortality. RESULTS: The observed age-specific incidence and mortality rates of CC closely match the data replicated by the model. The model predicts that with a 90% vaccine coverage rate, CC cases and mortality would be reduced by 70%. In the base-case analysis with a discount rate of 3% the incremental cost per quality-adjusted life-years (QALY) gained, from a healthcare perspective, was €17,294. Without discounting this value is €2,591/QALY gained. CONCLUSIONS: The analysis suggests that implementing prophylactic CC vaccination within the current screening system would substantially reduce CC cases and deaths, as well as the overall disease burden expressed in pre-cancer lesions averted. Vaccination could be a cost-effective intervention in Finland despite the fact that the number of CC cases and deaths are currently relatively low. Conservative estimates of the cost effectiveness of the vaccination were provided since it was not possible to assess herd protection induced by vaccination using this Markov model.