Long-term health care resource and cost savings with allergy immunotherapy: REACT study results.

Background: Allergy immunotherapy (AIT) can be administered as subcutaneous immunotherapy (SCIT) injections in the clinic or as sublingual immunotherapy (SLIT) tablets at home after initiation under medical supervision. To achieve long-term, sustained effects, a 3-year treatment duration is recommended. Objective: Our aim was to assess the association of AIT (SCIT and SLIT tablets) with long-term health care resource use (HRU) and costs in subjects with allergic rhinitis. Methods: REACT was a retrospective propensity score-matched cohort study using claims data from a German health insurance database (2007-2017), with up to 9 years of follow-up after AIT initiation. HRU and costs were evaluated for hospitalizations, ambulatory care visits, and prescriptions, in subjects who received AIT versus in matched controls with allergic rhinitis who had not received AIT, as well as for SCIT and SLIT tablets. Results: Across all 9 years, the subjects who received AIT had a significantly lower incidence of hospitalization than the controls did. Generally, proportions of subjects with ambulatory care visits and hospitalizations were lower, and length of hospitalization was shorter, for those receiving SLIT tablets than those who received SCIT. Total costs were significantly higher with AIT versus for the controls during the treatment period (years 1 to 3), driven by prescriptions and ambulatory care visits, but they were lower in years 4 to 9. During years 1 to 3, prescription costs were generally higher for SLIT tablets than for SCIT, whereas ambulatory care costs were numerically lower. In most years, hospitalization costs were numerically lower for SLIT tablets than for SCIT. Conclusion: Initial higher HRU and costs of AIT during the expected treatment period are offset in the long term. At-home administration of SLIT tablets may further reduce ambulatory care costs.

High baseline prevalence of atopic comorbidities and medication use in children treated with allergy immunotherapy in the REAl-world effeCtiveness in allergy immunoTherapy (REACT) study.

Background: Respiratory allergy, commonly manifesting as allergic rhinitis (AR) and asthma, is a chronic progressive disease that frequently starts in childhood. Allergy immunotherapy (AIT) is the only causal treatment for respiratory allergy with the potential to modify the underlying cause of allergy and, ultimately, prevent disease progression. This analysis aimed to determine if AIT is received sufficiently early to halt the progression of allergic disease, by characterizing the burden and progression of disease in children prior to AIT initiation in real-life clinical practice. Methods: The REAl-world effeCtiveness in allergy immunoTherapy (REACT) study was a large retrospective cohort study using German claims data between 2007 and 2017. Characteristics of two pre-defined AIT age cohorts from the REACT study - children (aged <18 years) and adults (aged ≥18 years) - were evaluated during the 1-year period before the first AIT prescription. For comparison, a control group of all subjects with a confirmed diagnosis of AR and without prescriptions for AIT was included. Burden of disease was assessed using diagnostic codes for atopic comorbidities [e.g., atopic dermatitis (AD), asthma, and acute allergic conjunctivitis] and non-atopic comorbidities (e.g., migraine, headache); medication use, recorded as prescriptions for symptom-relieving AR medication and reliever/controller medication for asthma, was also assessed. Data were analyzed descriptively, using summary statistics. Results: Both children (n = 11,036) and adults (n = 30,037) showed a higher prevalence of atopic comorbidities and a greater drug burden prior to AIT initiation compared to AR patients not treated with AIT (n = 1,003,332). In the two age-specific AIT cohorts, children consistently showed the highest prevalence of atopic comorbidities compared to adults (AIT children, AIT adults - asthma: 41.4%, 34.5%; AD: 19.9%, 10.2%; acute allergic conjunctivitis: 13.6%, 10.2%). Generally, prescriptions per year for symptom-relieving AR and asthma treatments were also higher for children initiating AIT vs. adults (AIT children, AIT adults - AR prescriptions per subject: 1.72, 0.73; asthma prescriptions per subject: 1.42, 0.79). Conclusions: Children with AR who are offered AIT in real-life show considerable disease burden prior to initiation. As AIT may alleviate the burden and halt the progression of allergic disease, considering AIT earlier in the disease course may be warranted.

Real-world, long-term effectiveness of allergy immunotherapy in allergic rhinitis: Subgroup analyses of the REACT study.

BACKGROUND: Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet. OBJECTIVE: We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet. METHODS: The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects. RESULTS: Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite-specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets. CONCLUSIONS: These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.

Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study.

BACKGROUND: Allergen immunotherapy (AIT) is the only causal treatment for respiratory allergy. Long-term real-life effectiveness of AIT remains to be demonstrated beyond the evidence from randomised controlled trials (RCTs). METHODS: REACT (Real world effectiveness in allergy immunotherapy) is a retrospective cohort study using claims data between 2007 and 2017. Study eligibility was a confirmed diagnosis of allergic rhinitis (AR), with or without asthma, and AIT. To ensure comparable groups, AIT-treated subjects were propensity score matched 1:1 with control subjects, using characteristic and potential confounding variables. Outcomes were analysed as within (pre vs post AIT) and between (AIT vs control) group differences across 9 years of follow-up (ClinicalTrial.gov: NCT04125888). FINDINGS: 46,024 AIT-treated subjects were matched with control subjects and 14,614 were included in the pre-existing asthma cohort. AIT-treated subjects were 29·5 (16·3) years and 53% were male. Compared to pre-index year, AIT was consistently associated with greater reductions compared to control subjects in AR and asthma prescriptions, including both asthma controller and reliever prescriptions. Additionally, the AIT group had significantly greater likelihood of stepping down asthma treatment (P <0·0001). In addition to the reduction in asthma treatment in the AIT group, a greater reduction in severe asthma exacerbations was demonstrated (P<0·05). Reductions in pneumonia with antibiotic prescriptions, hospitalisations, and duration of inpatients stays were all in favour of AIT. INTERPRETATION: The study extends the existing RCT evidence for AIT by demonstrating longer-term and sustained effectiveness of AIT in the real world. Additionally, in patients with concurrent asthma, AIT was associated with reduced likelihood of asthma exacerbations and pneumonia. FUNDING: The study was funded by ALK A/S.

The impact of moderate and severe asthma exacerbations on quality of life: a post hoc analysis of randomised controlled trial data.

BACKGROUND: This paper reports the duration of moderate and severe exacerbations in patients with house dust mite induced allergic asthma and the impact on patients' quality of life. METHODS: Post-hoc analyses were conducted using data collected during a phase III multi-national trial (MT-04) that investigated time to moderate or severe asthma exacerbation among 485 patients during withdrawal from inhaled corticosteroids. Patient diaries were analysed to ascertain duration of exacerbations. The impact on patients' quality of life was measured by calculating utilities for five health states using the EuroQol-5 Dimension (EQ-5D-3L) and Asthma Quality of Life Questionnaire (AQL-5D). A regression analysis predicted the disutility of moving from 'well controlled asthma' to the other four health states: 'partially controlled asthma', 'uncontrolled asthma', 'moderate exacerbation' and 'severe exacerbation'. RESULTS: Two hundred four patients experienced exacerbations. Moderate and severe exacerbations involved statistically significant reductions in lung function compared to the constant peak expiratory flow observed for patients without exacerbations. Lung function decline occurred for 28 days, decreasing approximately 14 days before an exacerbation followed by a return to baseline over 14 days. Asthma symptoms, the use of short-acting ß2-agonists, and frequency of nocturnal awakening all increased, starting 10-14 days before an exacerbation, and returned to baseline within 10-28 days following exacerbations. Compared to 'well controlled asthma', the disutility of having a 'moderate exacerbation' ranged from - 0.0834 to - 0.0921 (EQ-5D-3L) and from - 0.114 to - 0.121 (AQL-5D); and of having a 'severe exacerbation' from - 0.115 to - 0.163 (EQ-5D-3L) and from - 0.153 to - 0.217 (AQL-5D), depending on the length of the observation period. CONCLUSIONS: The impact of moderate and severe exacerbations in house dust mite induced allergic asthma extends 14 days before and 28 days after the peak exacerbation event. The impact of exacerbations on patients' health-related quality of life (HRQoL) continues long after their occurrence.

A quality-of-life mapping function developed from a grass pollen sublingual immunotherapy trial to a tree pollen sublingual immunotherapy trial.

Aims: Allergic rhinitis is caused by sensitivity to environmental allergens that can significantly impact quality-of-life. The objective of this analysis was to estimate health state utilities and quality-adjusted life days (QALDs) for a tree allergy immunotherapy trial, TT-04 (EudraCT No.2015-004821-15). Health-state utilities are a measure of patient preference for health states and are necessary to derive QALDs for cost-utility analysis. Preference-based utilities were not collected in the TT-04 trial, so a mapping algorithm was developed based on a similar grass allergy immunotherapy trial, GT-08 (EudraCT No. 2004-000083-27), to estimate utilities.Methods: A two-part model was developed to predict utilities for the GT-08 trial and applied to the TT-04 trial to estimate the difference in mean utility and QALDs between SQ tree sublingual immunotherapy (SLIT)-tablet and placebo.Results: Mean utility difference between SQ tree SLIT-tablet and placebo was 0.030 [95% CI = 0.015-0.046] during the birch pollen season (BPS), 0.019 [95% CI = 0.007-0.030] during the tree pollen season (TPS) and 0.018 [95% CI = 0.007-0.030] during the full trial. The treatment showed a QALD benefit of 1.26 [95% CI = 0.619-1.917] during the BPS, 1.90 [95% CI = 0.692-3.047] during the TPS, and 2.47 [95% CI = 0.930-4.101] during the full trial.Limitations: The generalizability of this algorithm is limited to allergy trials containing the same covariates as those present in the model. The analysis also assumes that grass and tree pollen allergy have the same relationship with EQ5D utilities, which is supported by the fact that both grass and tree pollen induce similar symptoms.Conclusions: Application of the mapping function enabled the calculation of QALDs associated with the treatment, with the caveat that data were extrapolated from grass seasonal allergy to tree seasonal allergy. The results showed a significant QALD benefit of the treatment over placebo in treatment of tree pollen-induced rhinoconjunctivitis.

The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.

Timing of Insulin Injections, Adherence, and Glycemic Control in a Multinational Sample of People with Type 2 Diabetes: A Cross-Sectional Analysis.

INTRODUCTION: We investigated the association of bolus insulin dose timing with demographics, adherence, diabetes education program participation, experience with hypoglycemic events, glycemic control, and patient preference among respondents with type 2 diabetes. METHODS: Adults with type 2 diabetes from 12 countries were recruited to a Web-based self-reported patient preference survey. Adherence was measured using an adapted Morisky Medication Adherence Scale questionnaire. RESULTS: In total 1483 respondents reported using bolus insulin with 58% (n = 864) dosing bolus insulin before meals (pre-meal cohort), 354 (24%) during or after meals (post-meal cohort), and 265 (18%) before, during, or after meals (mixed cohort). The mixed cohort was excluded, thus 1218 respondents were included in the analysis. Respondent distribution across HbA1c category differed significantly depending on insulin dose timing (p = 0.0006); more respondents in the post-meal cohort (40%) had HbA1c ≥ 9% (74.9 mmol/mol) than in the pre-meal cohort (29%). The post-meal cohort was significantly more likely to report non-adherence than the pre-meal cohort (OR = 1.50, p = 0.01) and significantly more often reported participating in diabetes education programs (p < 0.05). Seventy-eight percent of all respondents reported preferring bolus insulin administrable whenever convenient. CONCLUSIONS: Approximately 24% of respondents never comply with guidelines for insulin dose timing, with higher risk of non-adherence and increased participation in diabetes care programs. Respondents dosing insulin post-meal are more likely to have poor glycemic control (HbA1c ≥ 9%, 74.9 mmol/mol). Given that many respondents had high HbA1c and were non-adherent, a treatment which satisfies patient preference for bolus insulin with flexible dose timing could be considered. FUNDING: Novo Nordisk.

Projected long-term outcomes in patients with type 1 diabetes treated with fast-acting insulin aspart vs conventional insulin aspart in the UK setting.

AIM: To assess the impact of faster aspart vs insulin aspart on long-term clinical outcomes and costs for patients with type 1 diabetes mellitus (T1DM) in the UK setting. METHODS: The QuintilesIMS CORE Diabetes Model was used to project clinical outcomes and costs over patient lifetimes in a cohort with data on baseline characteristics from the "onset 1" trial. Treatment effects were taken from the 26-week main phase of the onset 1 trial, with costs and utilities based on literature review. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: Projections indicated that faster aspart was associated with improved discounted quality-adjusted life expectancy (by 0.13 quality-adjusted life-years) vs insulin aspart. Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset with faster aspart. Faster aspart was found to be associated with reduced costs vs insulin aspart (cost savings of £1715), resulting from diabetes-related complications avoided and reduced treatment costs. CONCLUSIONS: Faster aspart was associated with improved clinical outcomes and cost savings vs insulin aspart for patients with T1DM in the UK setting.

Maintenance of weight loss or stability in subjects with obesity: a retrospective longitudinal analysis of a real-world population.

OBJECTIVES: Characterize patterns of weight change among subjects with obesity. METHODS: A retrospective observational longitudinal study of subjects with obesity was conducted using the General Electric Centricity electronic medical record database. Subjects who were ≥18 years old with BMI ≥30 kg/m2 (first defining index BMI), had no medical conditions associated with unintentional weight loss, and had ≥4 BMI measurements/year for ≥2.5 years were included and categorized into groups (stable weight: within <5% of index BMI; modest weight loss: ≥5 to <10% of index BMI lost; moderate weight loss: ≥10 to <15% of index BMI lost; and high weight loss: ≥15% of index BMI lost) based on weight change during 6 months following index. No interventions were considered. Patterns of weight change were then assessed for 2 years. RESULTS: A total of 177,743 subjects were included: 85.1% of subjects were in the stable weight, 9.3% in the modest, 2.3% in the moderate, and 3.3% in the high weight loss groups. The proportion of subjects who maintained or continued to lose weight decreased over the 2 year observation period; 11% of those with high weight loss continued to lose weight and 19% maintained their weight loss. This group had the lowest percentage of subjects who regained ≥50% of lost weight and the lowest proportion of subjects with weight cycling (defined as not continuously losing, gaining, or maintaining weight throughout the 2 year observation period relative to its beginning). This trend persisted in subgroups with class II-III obesity, pre-diabetes, and type 2 diabetes. CONCLUSION: Weight cycling and regain were commonly observed. Subjects losing the most weight during the initial period were more likely to continue losing weight.

Budget impact of treating commercially insured type 1 and type 2 diabetes patients in the United States with insulin degludec compared to insulin glargine.

OBJECTIVE: To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal-bolus therapy (T1DMBBT), type 2 diabetes mellitus patients on basal-oral therapy (T2DMBOT), and type 2 diabetes mellitus patients on basal-bolus therapy (T2DMBBT) switched from insulin glargine (IGlar) to insulin degludec (IDeg). METHODS: A short-term (1 year) budget impact model was developed to evaluate the costs of IDeg vs. IGlar in three treatment groups (T1DMBBT, insulin-naïve T2DMBOT, and T2DMBBT) through a simulation for a potential US health plan population of 35 million. The analysis captured direct medical costs associated with insulin treatment (insulin, needles, and self-monitored glucose testing) and costs related to managing hypoglycemic episodes. There were a total of 59,780 T1DMBBT patients, 383,145 T2DMBOT patients, and 171,325 T2DMBBT patients expected to be using long-acting insulin. A sensitivity analysis on the entire US population was also conducted. RESULTS: Among T1DMBBT patients, IDeg was associated with an annual cost savings of -$357.13 per patient per year (PPPY), driven primarily by reduced insulin utilization. IDeg was also found to be cost saving among T2DMBOT patients (-$1206.61 PPPY), driven primarily by reductions in the cost of treating severe hypoglycemic episodes. Among T2DMBBT patients, IDeg was associated with an additional cost to the plan of $1420.04 PPPY; however, this result was driven by a higher insulin dose for IDeg compared to IGlar. Overall, IDeg demonstrated cost savings of $240 million per year, which accounted for total cost savings of 3.5% vs. IGlar. CONCLUSIONS: The results of this analysis suggest that the reduced insulin utilization and fewer hypoglycemic episodes associated with IDeg may translate into reduced costs for payers. The model is limited by simplification of a complex disease state and assumptions surrounding disease state, treatment patterns, and costs. Therefore, results may not accurately reflect actual health plans or real-world practice patterns.