Longitudinal patterns of intermittent oral corticosteroid therapy for asthma in the United Kingdom.

Background: Increasing frequency of intermittent oral corticosteroid (OCS) prescription and cumulative OCS exposure increase the risk of OCS-related adverse outcomes. Objective: We sought to describe the evolution and trajectory of intermittent OCS prescription patterns in patients with asthma and investigate risk factors independently associated with transitioning to a frequent prescription pattern. Methods: This historical cohort study included patients with active asthma managed in UK primary care and included in the Optimum Patient Care Research Database (OPCRD; opcrd.co.uk). Intermittent OCS prescription patterns were categorized as sporadic, infrequent, moderately frequent, or frequent. Prescription pattern sequences were described for those who had a frequent sequence in their final year of prescribing. We examined associations between OCS prescription pattern and the hazard of transitioning into a frequent intermittent OCS prescription pattern using multivariable Cox regression with a 10-year look-back period. Results: Of 105,229 patients with intermittent OCS prescriptions, 57.1% (n = 60,083) had a frequent OCS prescription pattern at some point. Irrespective of baseline pattern, most patients transitioned to frequent prescription during the look back. The strongest risk factors were a more frequent prescription pattern at the start of look-back period, a lower percentage peak expiratory flow rate, and higher Global Initiative for Asthma treatment step. Older age, female sex, obesity, and active smoking were also associated with a higher risk of transitioning. Conclusion: Our findings help identify those most at risk of transitioning to frequent intermittent OCS receipt and encourage earlier intervention with OCS-sparing treatments.

Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. METHODS: We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. RESULTS: Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90 days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5 mg/day), patients on high-dose SCS (≥ 7.5 mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. CONCLUSIONS: Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Healthcare Resource Use and Costs Associated with Organ Damage in Newly Diagnosed Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis compared healthcare resource use (HCRU) and costs associated with incident organ damage in a cohort of adult patients with systemic lupus erythematosus (SLE). METHODS: Incident SLE cases were identified (Clinical Practice Research Datalink [CPRD] and Hospital Episode Statistics-linked healthcare databases; January 1, 2005-June 30, 2019). Annual incidence of 13 organ damage domains was calculated from SLE diagnosis through follow-up. Annualized HCRU and costs were compared between organ damage and non-organ damage patient groups using generalized estimating equations. RESULTS: A total of 936 patients met the inclusion criteria for SLE. Mean age was 48.0 (standard deviation [SD] 15.7) years and 88% were female. Over a median follow-up period of 4.3 (interquartile range [IQR] 1.9-7.0) years, 59% (315/533) had evidence of post-SLE diagnosis incident organ damage (≥ 1 type), which was greatest for musculoskeletal (146/819 [18%]), cardiovascular (149/842 [18%]), and skin (148/856 [17%]) domains. Patients with organ damage had greater resource use for all organ systems, excluding gonadal, versus those without it. Overall, mean (SD) annualized all-cause HCRU was greater in patients with organ damage versus those without it (inpatient, 1.0 versus 0.2; outpatient, 7.3 versus 3.5; accident and emergency, 0.5 versus 0.2 days; primary care contacts, 28.7 versus 16.5; prescription medications, 62.3 versus 22.9). Adjusted mean annualized all-cause costs were significantly greater in both post- and pre-organ damage index periods for patients with organ damage versus those without it (all P < 0.05, excluding gonadal). Overall organ damage was associated with significantly increased adjusted mean annualized per-patient cost (£4442 greater [P < 0.0001]) ranging between £2709 and £7150 greater depending on the organ damage type. CONCLUSION: Organ damage was associated with higher HCRU and healthcare costs, before and after SLE diagnosis. More effective SLE management may slow disease progression, prevent organ damage onset, improve clinical outcomes, and reduce healthcare costs.

Cost-effectiveness of tezepelumab in Canada for severe asthma.

AIMS: To assess the cost-effectiveness of tezepelumab as add-on maintenance therapy compared with standard of care (SoC) for the treatment of patients with severe asthma in Canada. MATERIAL AND METHODS: A cost utility analysis was conducted using a Markov cohort model with five health states ("controlled asthma", "uncontrolled asthma", "previously controlled asthma with exacerbation", "previously uncontrolled asthma with exacerbation", and "death"). Tezepelumab plus SoC was compared to SoC (high-dose inhaled corticosteroids plus long-acting beta agonist) using efficacy estimates derived from the NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) trials. The model included the costs of therapy, administration, resource use for disease management, and adverse events. Utility estimates were calculated using a mixed-effects regression analysis of the NAVIGATOR and SOURCE trials. A Canadian public payer perspective was used with a 50-year time horizon, a 1.5% annual discount rate, and the base case analysis was conducted probabilistically. A key scenario analysis assessed the cost-effectiveness of tezepelumab compared with currently reimbursed biologics informed by an indirect treatment comparison. RESULTS: The base case analysis suggested that tezepelumab plus SoC was associated with a quality-adjusted life-year (QALY) gain of 1.077 compared with SoC alone at an incremental cost of $207,101 (2022 Canadian dollars), resulting in an incremental cost-utility ratio of $192,357/QALY. The key scenario analysis demonstrated that tezepelumab was dominant against all currently reimbursed biologics, with higher incremental QALYs (ranging from 0.062 to 0.407) and lower incremental costs (ranging from -$6,878 to -$1,974). Additionally, when compared against currently reimbursed biologics in Canada, tezepelumab had the highest probability of being cost-effective across all willingness-to-pay (WTP) thresholds. CONCLUSION: Tezepelumab provided additional life years and QALYs at additional cost compared with SoC in Canada. In addition, tezepelumab dominated (i.e. more effective, less costly) the other currently reimbursed biologics.

Healthcare costs associated with short-acting ß2-agonists in asthma: observational UK SABINA study.

BACKGROUND: Poor asthma control is associated with high short-acting ß2-agonist (SABA) use. AIM: To assess asthma-related healthcare resource utilisation (HCRU) and medication costs associated with high versus low SABA prescriptions in the UK. DESIGN & SETTING: Analysis of SABINA I (SABA use IN Asthma I), a retrospective longitudinal study using UK electronic health records (Clinical Practice Research Datalink GOLD 2008-2019 and Hospital Episode Statistics database). METHOD: Eligible patients were ≥12 years old with SABA prescriptions in the past year. SABA prescriptions (number of canisters per year) were defined as high (≥3) or low (1-2). Association of SABA prescriptions with HCRU was assessed by negative binominal model adjusted for covariates. The UK unit costs from the NHS were applied to estimate total healthcare costs (2020). Medication costs were based on the annual average number of canisters per year per patient. RESULTS: Overall, 186 061 patients with SABA prescriptions were included, of whom 51% were prescribed high SABA. Total annual average costs (HCRU and medication) were 52% higher in the high SABA group versus the low SABA group (£2 256 091 per 1000 patients/year versus £1 480 640 per 1000 patients/year). Medication costs accounted for the majority of asthma-related costs. Across both groups, most HCRU costs were for non-exacerbation-related primary care or hospital outpatient visits. The annual average HCRU cost difference for high SABA versus low SABA was the greatest for hospitalisations (+230%; £15 521 per 1000 patients/year versus £4697 per 1000 patients/year) and exacerbation-related primary care visits (+162%; £18 770 per 1000 patients/year versus £7160 per 1000 patients/year). Asthma-related HCRU extrapolated to the broader UK asthma population was £108.5 million per year higher with high SABA versus low SABA. CONCLUSION: High SABA versus low SABA prescriptions are associated with higher asthma-related HCRU costs.

The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK.

BACKGROUND: As-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting ß2-agonist (SABA). METHODS: A probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 µg or twice-daily budesonide 200 µg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses. RESULTS: On average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates. CONCLUSIONS: From a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.

Cost-effectiveness of roflumilast as an add-on to triple inhaled therapy vs triple inhaled therapy in patients with severe and very severe COPD associated with chronic bronchitis in the UK.

Purpose: Patients with severe COPD are at high risk of experiencing disease exacerbations, which require additional treatment and are associated with elevated mortality and increased risk of future exacerbations. Some patients continue to experience exacerbations despite receiving triple inhaled therapy (ICS plus LAMA plus LABA). Roflumilast is recommended by the Global Initiative for Chronic Obstructive Lung Disease as add-on treatment to triple inhaled therapy for these patients. This cost-effectiveness analysis compared costs and quality-adjusted life-years for roflumilast plus triple inhaled therapy vs triple inhaled therapy alone, using data from the REACT and RE2SPOND trials. Patients and methods: Patients included in the analysis had severe to very severe COPD, FEV1 <50% predicted, symptoms of chronic bronchitis and ≥2 exacerbations per year. Our model was adapted from a previously published and validated model, and the analyses conducted from a UK National Health Service perspective. A scenario analysis considered a subset of patients who had experienced at least one COPD-related hospitalization within the previous year. Results: Roflumilast as add-on to triple inhaled therapy was associated with non-significant reductions in rates of both moderate and severe exacerbations compared with triple inhaled therapy alone. The incremental cost-effectiveness ratio (ICER) for roflumilast as add-on to triple inhaled therapy was £24,976. In patients who had experienced previous hospitalization, roflumilast was associated with a non-significant reduction in the rate of moderate exacerbations, and a statistically significant reduction in the rate of severe exacerbations. The ICER for roflumilast in this population was £7,087. Conclusions: Roflumilast is a cost-effective treatment option for patients with severe or very severe COPD, chronic bronchitis, and a history of exacerbations. The availability of roflumilast as add-on treatment addresses an important unmet need in this patient population.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population.

BACKGROUND: Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. AIMS: We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. METHODS: This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting ß2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. RESULTS: Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). CONCLUSIONS: Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

What can we learn from Italian lessons?

Italy is well-known for its creative flair and contemporary design, but does this creativity translate to the healthcare sector? Having recently visited several Italian hospitals, Danny Gibson, technical director at international healthcare consultancy MJ Medical, contrasts the Italian healthcare system's use of equipment and technology with the UK approach, considers Italian hospital planners' attitude to future-proofing their buildings, and asks what lessons, if any, the UK can learn.