An expert panel's review on patients with hereditary angioedema switching from attenuated androgens to oral prophylactic therapy.

Background: Hereditary angioedema (HAE) is a rare condition marked by swelling episodes in various body parts, including the extremities, upper airway, face, intestinal tract, and genitals. Long-term prophylaxis (LTP), prescribed to control recurring HAE attacks, is integral to its management. Previously, attenuated androgens (AAs) were the only oral LTP options. However, in 2020, berotralstat, an oral plasma kallikrein inhibitor, was approved in the United States. A 2018 survey of adults with HAE type I or type II showed that almost all the patients who used prophylactic HAE medication preferred oral treatment (98%) and felt that it fit their lifestyle better than injectable treatment (96%). Still, guidelines lack consensus on transitioning patients from AAs to alternative oral prophylactic therapy. Objective: This paper aims to share expert insights and patient feedback on transitioning from AAs to berotralstat, an alternative oral prophylactic therapy, from the perspective of clinicians with extensive experience in treating patients with HAE. Methods: A panel of five HAE specialists convened for a virtual half-day roundtable discussion in April 2023. Results: Discussions about transitioning from AAs to berotralstat were prompted by routine consultations, patient inquiries based on independent research, ineffective current treatment, or worsening AA-related adverse effects. For patients who switched from AAs, the physicians reported that the decision was influenced by the alternative therapy's ability to prevent HAE attacks, its safety, and the once-daily administration schedule. All expert panel members identified fewer AA-related adverse effects; better quality of life; and less severe, shorter, and less frequent HAE attacks as clinical or patient goals they hoped to achieve through the treatment switch. Conclusion: The emergence of new, highly specific LTP drugs for HAE calls for the development of comprehensive recommendations and guidelines for transitioning from AAs to alternative oral prophylactic therapy. The expert panel highlighted key factors to consider during the development of such guidelines.

Healthcare utilization, quality of life, and work productivity associated with primary hyperoxaluria: a cross-sectional web-based US survey.

Primary hyperoxaluria (PH) is a family of ultra-rare, autosomal recessive, metabolic disorders associated with frequent kidney stones, chronic kidney disease and kidney failure, and serious complications due to systemic oxalosis, resulting in significant morbidity. We investigated the burden of PH among affected patients and caregivers. This cross-sectional, web-based survey was used to quantify the burden of PH, in terms of healthcare resource utilization, health-related quality of life, and work productivity and activity impairment among adults (≥ 18 years) with PH and caregivers of children (≤ 17 years) with PH in the US. Among the 20 respondents, there were 7 adults with PH and 13 caregivers of children with PH. Adherence to hyperhydration was noted as the most, or one of the most, difficult aspects of PH by 56% of respondents. Most patients (95%) had experienced painful kidney stone events, one-third had visited the emergency room, and 29% were hospitalized for complications due to PH. Of the 24% of patients on dialysis, all found the procedure burdensome. Adult patients' quality of life was negatively affected across several domains. Most respondents (81%) reported that PH had a negative effect on their finances. Employed adult patients and caregivers, and children with PH, had moderate impairment in work productivity, school attendance, and activity. Anxiety about future PH-related sequelae was moderate to high. These findings highlight the need for improvements in PH medical management. A plain language summary is available in the supplementary information.

The burden associated with thrombocytopenia and platelet transfusions among patients with chronic liver disease.

Background: Thrombocytopenia (TCP), a common complication of chronic liver disease (CLD), can cause uncontrolled bleeding during procedures. As such, CLD patients with TCP and platelet counts <50,000/µL often receive prophylactic platelet transfusions before invasive procedures. However, platelet transfusions are associated with clinical complications, which may result in increased healthcare utilization and costs.Objective: This retrospective database analysis describes the clinical and economic burden in CLD patients with TCP, CLD patients without TCP, and CLD patients with TCP who receive platelet transfusions.Methods: Adult CLD patients with or without TCP were identified in the IBM MarketScan Commercial Claims and Medicare Supplemental data from 1 January 2012 to 31 December 2015. CLD patients with or without TCP were propensity-score matched (1:1) for the analysis of annual healthcare utilization and costs. Platelet transfusions among CLD patients with TCP were identified using procedure codes.Results: Of the 601,626 patients with CLD, 8,292 (1.4%) patients with TCP were matched to patients without TCP. Among CLD patients with TCP, 981 (11.8%) patients received ≥1 platelet transfusions and met inclusion/exclusion criteria. Compared to patients without TCP, CLD patients with TCP had more complications, including higher prevalence of neutropenia (11.4% vs 2.9%) and bleeding events (21.4% vs 10.9%), greater resource utilization including greater average hospital admissions (1.2 vs 0.7, p < .01), greater average ER visits (2.1 vs 1.3, p < .01), higher average outpatient office visits (20.1 vs 18.4, p < .01), and higher average healthcare costs including total costs (p < .01), inpatient costs (p < .01), ER visit costs (p < .01), and outpatient office visit costs (p < .01). The mean annual total costs in CLD and TCP patients with platelet transfusions were $206,396.Conclusions: CLD patients with TCP, and particularly those who received platelet transfusions, experienced significantly greater clinical and economic burden compared to CLD patients without TCP. Safer and more cost-effective treatments to increase platelets are necessary.

Impact of Site of Care on Infection Rates Among Patients with Primary Immunodeficiency Diseases Receiving Intravenous Immunoglobulin Therapy.

PURPOSE: Patients with primary immunodeficiency diseases (PIDD) are at increased risk of infection and may require lifelong immunoglobulin G (IgG) replacement. Infection incidence rates were determined for patients with PIDD receiving intravenously administered IgG (IGIV) in a home or hospital outpatient infusion center (HOIC). METHODS: Data were extracted from a large, US-based, employer-sponsored administrative database. Patients were eligible for analysis if they had ≥1 inpatient or emergency room claim or ≥2 outpatient claims with a PIDD diagnosis between January 2002 and March 2013, 12 months of continuous health plan enrollment prior to index date (i.e., first IGIV infusion date), and 6 months of continuous IGIV at the same site of care after the index date. Incidences of pneumonia (bacterial or viral) and bronchitis (all types) within 7 days of IGIV infusion were retrospectively determined and compared between sites of care. RESULTS: A total of 1076 patients were included in the analysis; 51 and 49% received IGIV at home and at an HOIC, respectively. The event/patient-year of pneumonia was significantly lower in patients receiving IGIV at home compared to an outpatient hospital (0.102 vs. 0.216, p = 0.0071). Similarly, the event/patient-year of bronchitis was significantly lower among patients infusing at home compared to an HOIC (0.150 vs. 0.288, p < 0.0001). CONCLUSIONS: PIDD patients experienced incidence rates for pneumonia and bronchitis that were lower for patients receiving home-based IGIV treatment versus HOIC-based IGIV treatment. The lower infection rates in the home setting suggest that infection risk may be an important factor in site of care selection.

Health-Related Quality of Life and Health Resource Utilization in Patients with Primary Immunodeficiency Disease Prior to and Following 12 Months of Immunoglobulin G Treatment.

PURPOSE: Health-related quality of life (HRQOL) has not been examined in patients with predominant antibody deficiency both pre- and post-immunoglobulin G (IgG) treatment initiation. HRQOL and health resource utilization (HRU) were assessed in newly diagnosed patients with primary immunodeficiency disease (PIDD) pre- and 12 months post-IgG treatment initiation. METHODS: Adults (age ≥18 years) completed the 36-item Short Form Health Survey, version 2; pediatric patients (PP)/caregivers completed the Pediatric Quality of Life Inventory (PedsQL). Scores were compared with normative data from the US general population (GP) and patients with other chronic conditions (OCC). RESULTS: Seventeen adult patients (APs), 8 PPs, and 8 caregivers completed baseline assessments. APs had significantly lower baseline mean physical component summary scores versus GP (37.4 vs 50.5, p < 0.01) adults with chronic back pain (44.1, p < 0.05) or cancer (44.4, p < 0.05) and lower mental component summary scores versus GP (41.6 vs 49.2, p < 0.05). PPs had lower PedsQL total (63.1 vs 82.7), physical summary (64.5 vs 84.5), and psychosocial summary (62.5 vs 81.7) scores versus GP. Post-IgG treatment, 14 APs, 6 PPs, and 8 caregivers completed assessments. Hospital admissions (0.2 versus 1.8, p < 0.01), serious infections (3.3 versus 10.9, p < 0.01) and antibiotic prescriptions (3.0 versus 7.1; p < 0.01) decreased significantly overall. While APs reported significant improvement in role-physical (p = 0.01), general health (p < 0.01), and social functioning (p = 0.02) and caregivers in vitality (p < 0.01), PPs did not. CONCLUSIONS: Pre-IgG treatment, patients with PIDD experienced diminished HRQOL versus GP and patients with OCC; post-treatment, HRU decreased and certain HRQOL aspects improved for APs and caregivers.

Impact of Alzheimer's Disease on Caregiver Questionnaire: internal consistency, convergent validity, and test-retest reliability of a new measure for assessing caregiver burden.

BACKGROUND: There is a lack of validated instruments to measure the level of burden of Alzheimer's disease (AD) on caregivers. The Impact of Alzheimer's Disease on Caregiver Questionnaire (IADCQ) is a 12-item instrument with a seven-day recall period that measures AD caregiver's burden across emotional, physical, social, financial, sleep, and time aspects. Primary objectives of this study were to evaluate psychometric properties of IADCQ administered on the Web and to determine most appropriate scoring algorithm. METHODS: A national sample of 200 unpaid AD caregivers participated in this study by completing the Web-based version of IADCQ and Short Form-12 Health Survey Version 2 (SF-12v2™). The SF-12v2 was used to measure convergent validity of IADCQ scores and to provide an understanding of the overall health-related quality of life of sampled AD caregivers. The IADCQ survey was also completed four weeks later by a randomly selected subgroup of 50 participants to assess test-retest reliability. Confirmatory factor analysis (CFA) was implemented to test the dimensionality of the IADCQ items. Classical item-level and scale-level psychometric analyses were conducted to estimate psychometric characteristics of the instrument. Test-retest reliability was performed to evaluate the instrument's stability and consistency over time. RESULTS: Virtually none (2%) of the respondents had either floor or ceiling effects, indicating the IADCQ covers an ideal range of burden. A single-factor model obtained appropriate goodness of fit and provided evidence that a simple sum score of the 12 items of IADCQ can be used to measure AD caregiver's burden. Scales-level reliability was supported with a coefficient alpha of 0.93 and an intra-class correlation coefficient (for test-retest reliability) of 0.68 (95% CI: 0.50-0.80). Low-moderate negative correlations were observed between the IADCQ and scales of the SF-12v2. CONCLUSIONS: The study findings suggest the IADCQ has appropriate psychometric characteristics as a unidimensional, Web-based measure of AD caregiver burden and is supported by strong model fit statistics from CFA, high degree of item-level reliability, good internal consistency, moderate test-retest reliability, and moderate convergent validity. Additional validation of the IADCQ is warranted to ensure invariance between the paper-based and Web-based administration and to determine an appropriate responder definition.

Patient and parent preferences for immunoglobulin treatments: a conjoint analysis.

OBJECTIVES: The purpose was to quantify patient and parent preferences for administration attributes of immunoglobulin (IG) treatments; and determine which administration attributes were most important to users of IG treatment and whether patients and parents have similar preferences for administration attributes. METHODS: US adult patients and parents of children with a self-reported physician diagnosis of a primary immunodeficiency disorder completed a best-practice web-enabled choice-format conjoint survey that presented a series of 12 choice questions, each including a pair of hypothetical IG-treatment profiles. After reviewing current therapies, each profile was defined by mode of administration, frequency, location, number of needle sticks, and treatment duration. Before answering the choice questions, respondents were told to assume all treatments worked equally well. Choice questions were based on a D-efficient experimental design. Preference weights for attribute levels were estimated using random-parameters logit for each sample (adult patients and parents). Tests were performed to determine potential interactions among the administration attributes. All respondents provided online informed consent. RESULTS: In total, 252 patients and 66 parents completed the choice questions appropriately. Overall, both groups preferred a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations of IG treatment relative to alternative choices (p<0.05). Mode of administration was the least important attribute to both samples; however, parents strongly preferred self-administration to an appointment with a healthcare professional (p<0.05), whereas patients slightly preferred self-administration but were indifferent to the two modes. LIMITATIONS: Respondents evaluate hypothetical treatments and differences can arise between stated and actual choices. CONCLUSIONS: Considering the hypothetical treatments evaluated, IG treatments that provide the option of a home setting, monthly frequency, fewer needle sticks, and shorter treatment durations may address the needs of both patients and parents. Patients and parents have different preferences for administration attributes of IG treatments.

Medical costs and resource utilization for hemophilia patients with and without HIV or HCV infection.

BACKGROUND: Previous research has shown that hemophilia patients infected in the 1980s with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV) from the blood supply have increased morbidity and mortality. Although the possibility of contracting HIV or HCV through contaminated blood products has been virtually eliminated in the United States, approximately one third of hemophiliacs between the ages of 21 and 60 years are HIV infected. OBJECTIVE: To determine the health care resource utilization of adult hemophilia patients with and without HIV and HCV infection in a commercially insured population in the United States. METHODS: This was a retrospective claims analysis of the PharMetrics Patient-Centric database over an approximately 7-year period from January 1997 to April 2004. The database represents about 43 million members in commercial health plans. Male patients continuously enrolled for at least 6 months and >18 years of age were included in the study; female patients were excluded since they were likely to have von Willebrand disease. Hemophilia patients were identified if they had at least 1 claim with a primary diagnosis of hemophilia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 286.XX) and at least 1 claim for a hemophilia drug (identified by National Drug Code number and J codes: J7190-J7199, Q0187 or Q2022). Clotting factor inhibitor patients identified through the dispensation of an activated prothrombin complex concentrate or recombinant factor VIIa were excluded from the study. Virally infected patients were identified as those hemophilia patients with at least 1 claim with a HIV diagnosis (ICD-9-CM codes 042.xx, 079.53) or HCV infection (ICD-9-CM codes 070.41, 070.44, 070.51, 070.54). Four cohorts for analysis were established: hemophilia without HIV or HCV coinfection (H-only); hemophilia + HIV (H + HIV); hemophilia + HCV (H + HCV); and hemophilia + HIV + HCV (H + HIV + HCV). The index date was defined as the first day of enrollment. Follow-up lasted until the end of the patient's enrollment or the end of the study period. The main outcomes of the study were (1) annualized net costs paid by health plans (after subtracting member cost-share) associated with all pharmacy and medical claims and (2) office visit distribution overall and by physician specialty during the study period. RESULTS: A total of 166 patients were identified for the study--73 with H-only, 12 with H + HIV, 44 with H + HCV, and 37 with H + HIV + HCV. The mean (median) annualized total cost of care in 2004 dollars was $90,942 ($63,613) for the H-only cohort versus $108,862 ($64,782, P = 0.512) for the H + HIV cohort; $104,404 ($66,489, P = 0.377) for the H+HCV cohort; and $144,462 ($111,542, P = 0.005) for the H + HIV + HCV coinfected cohort. Clotting factor accounted for 78% - 86% of total health care costs for all 4 groups of patients. Compared with the H-only cohort ($2,136), the H + HIV, H + HCV, and H + HIV + HCV cohorts had significantly higher mean non-hemophilia prescription drug costs ($8,239 [P = 0.001]; $7,275 [P = 0.034]; and $12,360 [P < 0.001], respectively). The H + HIV + HCV cohort had significantly higher hospital inpatient costs than did the H-only cohort ($5,655 vs. $3,360, respectively, P = 0.015). Mean annualized outpatient costs were higher in the H + HIV + HCV cohort ($12,897, P < 0.001) and H + HCV cohort ($7,233, P = 0.016) than in the H-only cohort ($7,216). Mean annualized total numbers of office visits were higher for the H + HCV (11.18, P = 0.003) and H + HIV + HCV (18.33, P < 0.001) cohorts than for the H-only cohort (6.98). Compared with the H-only cohort, the H + HIV + HCV cohort had a greater mean annualized number of visits to infectious disease specialists (3.75 vs. 0.12, P < 0.001) and to gastroenterology specialists (1.22 vs. 0.09, P < 0.001). CONCLUSION: The presence of HIV and HCV coinfection in hemophiliacs is associated with 59% (95% confidence interval, 34.8%, 82.9%) greater annual health care costs compared with costs for hemophilia alone. Coinfection with HIV and HCV is associated with significantly greater component costs for clotting factor, prescription drugs, inpatient services, and outpatient services.