Healthcare utilization of patients with hereditary angioedema treated with lanadelumab and subcutaneous C1-inhibitor concentrate.

Background: New hereditary angioedema (HAE) treatments have become available in recent years for the treatment of HAE due to C1-inhibitor (C1-INH) deficiency, including two subcutaneous (SC) options: a monoclonal antibody (lanadelumab) and a plasma-derived C1-INH concentrate (SC-C1-INH). Limited real-world data on these therapies have been reported. Objective: The objective was to describe new users of lanadelumab and SC-C1-INH, including demographics, healthcare resource utilization (HCRU), costs, and treatment patterns before and after beginning treatment. Methods: This was a retrospective cohort study that used an administrative claims data base. Two mutually exclusive cohorts of adult (ages ≥18 years) new users of lanadelumab or SC-C1-INH with ≥180 days of continuous use were identified. HCRU, costs, and treatment patterns were assessed in the 180-day period before the index date (new treatment use) and up to 365 days after the index date. HCRU and costs were calculated as annualized rates. Results: Forty-seven patients who used lanadelumab and 38 patients who used SC-C1-INH were identified. The most frequently used on-demand HAE treatments at baseline were the same for both cohorts: bradykinin B2 antagonists (48.9% of the patients on lanadelumab, 52.6% of the patients on SC-C1-INH) and C1-INHs (40.4% of the patients on lanadelumab, 57.9% of the patients on SC-C1-INH). More than 33% of the patients continued to fill on-demand medications after treatment initiation. Annualized angioedema-associated emergency department visits and hospitalizations decreased after initiation of treatment, from 1.8 to 0.6 for the patients on lanadelumab and from 1.3 to 0.5 for the patients on SC-C1-INH. Annualized total healthcare costs after treatment initiation in the database were $866,639 and $734,460 for the lanadelumab and SC-C1-INH cohorts, respectively. Pharmacy costs accounted for >95% of these total costs. Conclusion: Although HCRU decreased after the initiation of treatment, angioedema-associated emergency department visits and hospitalizations and on-demand treatment fills were not completely eliminated. This indicates ongoing disease and treatment burden despite use of modern HAE medicines.

Early real-world experience with emicizumab and concomitant factor VIII replacement products in adult males with Hemophilia A without inhibitors.

AIMS: To assess real-world use of emicizumab in adult people with hemophilia A (PwHA) without inhibitors including healthcare resource utilization (HCRU) and costs. MATERIALS AND METHODS: Adult, male PwHA without inhibitors initiating emicizumab (index date) were identified using IBM MarketScan after 4 October 2016. Patients were required to have continuous health insurance coverage for ≥180 days prior to and ≥90 days after index date and have ≥90 days of continuous use of emicizumab. Patients were followed until treatment gap, disenrollment, or end of data. Results were reported overall and among a subgroup with prior factor VIII (FVIII) prophylaxis. Emicizumab use, concomitant FVIII treatment use, HCRU, and costs were assessed separately over baseline, the emicizumab induction period, emicizumab maintenance period, and annualized. RESULTS: Among the 71 emicizumab patients (FVIII prophylaxis subgroup: 52) included in the study, the mean age was 35 (subgroup: 34) years and mean follow-up was 12 (subgroup: 11.1) months. At baseline, the annualized mean total healthcare cost was $532,948 (subgroup: $645,727). After emicizumab initiation, per-patient-per-month (PPPM) HCRU was higher in the emicizumab induction period compared to the maintenance period with higher monthly FVIII fills/in-office administrations (0.37 vs 0.17), non-FVIII outpatient visits (2.23 vs 1.55), and emergency department visits (0.06 vs 0.03). The FVIII prophylaxis subgroup yielded similar HCRU trends. Hemophilia treatment costs accounted for over 95% of total healthcare costs. The annualized mean cost was $50,491 (subgroup: $61,512) for concomitant FVIII treatment and $777,171 (subgroup: $793,168) for emicizumab and concomitant FVIII treatment for the first year of emicizumab treatment. CONCLUSION: This study represented experience with emicizumab after the approval for PwHA without inhibitors. The study cohort may not be representative of all PwHA taking emicizumab. The findings highlight the continued burden of treatment and healthcare cost for PwHA without inhibitors despite advances in treatment options.

Treatment effectiveness in a rare oncology indication: Lessons from an external control cohort study.

Real-world data (RWD) reflecting patient treatment in routine clinical practice can be used to develop external control groups for single-arm trials. External controls can provide valuable benchmark results on potential comparator drug effectiveness, particularly in rare indications when randomized controlled trials are either infeasible or unethical. This paper describes lessons learned from a descriptive real-world external control cohort study conducted to provide benchmark data for a single-arm clinical trial in a rare oncology biomarker driven disease. Conducting external control cohort studies to evaluate treatment effectiveness in rare indications likely will present data and analysis challenges as seen in the example study. However, there are mitigating measures that can be applied in the study design, identification of RWD sources, and data analysis. The lessons learned and reported here with a proposal of an external control study framework can provide guidance for future research in this area, and may be applicable as well in other rare indications. Taking these learnings into consideration, the use of real-world external controls to contextualize treatment effectiveness in rare indications is a valuable approach and warrants further application in the future.

Economic burden of joint analysis in psoriasis: US claims analysis.

OBJECTIVES: Few studies have assessed the economic burden of concomitant joint disease in patients with psoriasis (PSO). This analysis compared health care resource utilization (HCRU) and health care costs in patients with PSO vs those with psoriatic arthritis (PsA). STUDY DESIGN: This was a retrospective database analysis of US commercially insured patients with PSO or PsA. METHODS: Electronic health records (EHRs) and claims in Optum's deidentified Integrated Claims-Clinical data set from 2007 to 2018 were analyzed. Patients were followed up from the first PSO or PsA diagnosis for up to 5 years. Patients with claims or diagnosis codes in EHR data for PSO ("PSO only") were propensity score matched to patients with claims/diagnosis codes for both PSO and PsA ("PSO-PsA"). RESULTS: The matching algorithm generated 4418 matched patient pairs. During follow-up, PSO-PsA patients had greater HCRU than PSO-only patients, including more cumulative all-cause outpatient claims (P ≤ .05 at each year of follow-up). Mean total annual health care costs per patient were higher in PSO-PsA patients than PSO-only patients (PSO only: $14,546-$15,800 vs PSO-PsA: $21,581-$22,868; P < .05 at each year of follow-up). All-cause outpatient and pharmacy costs were also higher in the PSO-PsA cohort (P < .05 at each year of follow-up). CONCLUSIONS: Comorbid joint disease in PSO is associated with greater costs and use of health care resources than PSO alone. These findings underscore the need for dermatologists to be vigilant about detection and treatment of joint symptoms. Early PsA diagnosis and therapy are crucial to improve patient outcomes and reduce the potential economic burden.

Clinical Burden of Concomitant Joint Disease in Psoriasis: A US-Linked Claims and Electronic Health Records Database Analysis.

BACKGROUND: Few studies have evaluated the clinical burden of concomitant joint disease in patients with psoriasis (PSO). The objective of this study was to assess comorbidity rates in patients with psoriatic arthritis (PsA) compared with PSO alone. METHODS: This was a retrospective study of US patients with prevalent PSO. Linked medical claims and electronic health records (EHR) in Optum's de-identified Integrated Claims-Clinical dataset were analyzed from 2007 to 2018. Patients were followed for up to 5 years after the first claim/diagnostic code for PSO (index date). Baseline comorbidity prevalence and follow-up rates (cases per 1000 person-years) were assessed using descriptive statistics. Comorbidity rate analysis included patients with the respective comorbidity at baseline. RESULTS: Baseline demographics and comorbidity prevalence were numerically similar between patients with concomitant joint disease (PSO-PsA) and those with PSO alone (PSO-only). During follow-up, comorbidity rates were higher in patients in the PSO-PsA group than patients in the PSO-only group. Ratios of PSO-PsA comorbidity rates relative to PSO-only ranged from 1.1 for allergies and infections to 1.7 for fatigue, diabetes, and obesity. Comorbidity rate ratios increased from year 1 to year 5 for hypertension (1.05-1.34), hyperlipidemia (0.94-1.13), diabetes (1.00-1.49), cardiovascular disease (1.03-1.66), depression (0.97-1.19), and anxiety (0.87-0.98). CONCLUSIONS: Patients with PsA have a larger clinical burden, characterized by higher comorbidity rates, than those with PSO. Future research should explore PsA risk factors and how physicians can monitor and treat patients with PSO to reduce the risk of PsA and the associated clinical burden.

Psoriasis is a disease that causes scaly, red skin patches that are itchy or painful. About one-third of people who have psoriasis also develop joint pain. This combination of skin symptoms and joint disease is known as psoriatic arthritis. Having psoriatic arthritis can have a greater effect on people's quality of life than having psoriasis alone. People with psoriasis or psoriatic arthritis often have other medical conditions that are not related to their skin or joints. We know that some conditions, such as obesity and high blood pressure, are more common in people with psoriatic arthritis than in those who only have psoriasis. However, more evidence is needed to understand if this pattern is also seen with other medical conditions. We used a large database of medical insurance claims and electronic health records to see what other medical conditions people with psoriatic arthritis or psoriasis had. We found that people with psoriatic arthritis were more likely to have other medical conditions than those with only psoriasis, including high blood pressure, obesity, diabetes, heart disease, and mental health conditions. These differences became larger over the years covered by this study (2007­2018). The results of this study show that people with psoriatic arthritis are more likely to have additional medical conditions than those who have psoriasis alone. Therefore, it is very important that doctors understand how to reduce the risk of joint disease in their patients with psoriasis.

Spiritual Well-Being in Hispanic and Non-Hispanic Survivors of Allogeneic Hematopoietic Stem Cell Transplantation.

Research suggests that spiritual well-being positively contributes to quality of life during and following cancer treatment. This relationship has not been well-described in ethnically diverse survivors of allogeneic transplantation.  This study compares spiritual well-being and quality of life of Hispanic (n = 69) and non-Hispanic (n = 102) survivors. Hispanic participants were significantly younger and reported significantly greater spiritual well-being than non-Hispanic survivors. Survivors with higher spiritual well-being had significantly better quality of life. Meaning and Peace significantly predicted quality of life. Although Hispanic survivors report greater spiritual well-being, Meaning and Peace, irrespective of ethnicity, have a salutary effect on quality of life.

A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation.

The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale-transplant and Brief Symptom Inventory-18. Active caregivers reported improvements in self-efficacy (p < 0.05) and distress (p < 0.01) post-problem-solving education; caregiver responders also reported better health outcomes such as fatigue. The effect of problem-solving education on self-efficacy and distress in hematopoietic stem cell transplantation caregivers supports its inclusion in future interventions to meet the multifaceted needs of this population.

Symptom distress predicts long-term health and well-being in allogeneic stem cell transplantation survivors.

The number of survivors after allogeneic hematopoietic stem cell transplantation (HSCT) continues to increase, yet their survivorship experience has not been fully characterized. This study examines the health status and health-related quality of life (HRQL) of HSCT survivors. The aims of the study were to: (1) explore the baseline and change over time in these health outcomes, and (2) characterize subgroups experiencing adverse outcomes. In this longitudinal study, adults who survived >3 years from date of allogeneic HSCT completed a series of patient-reported outcome measures annually, including measures of health status, HRQL, and symptoms. Data were analyzed using hierarchical linear modeling. Subjects (N = 171) were on average 44 (±13.5) years of age and primarily male (62.6%); 40% were Hispanic. Mean scores for physical and mental health and HRQL were preserved relative to population norms. Hierarchical linear modeling revealed no significant change in the mean trajectories of these outcomes, although significant between-individual variability was observed. When controlling for demographic and clinical factors, physical symptom distress negatively affected all outcomes. The impact of symptom distress on physical health varied based on time since HSCT; impairment in physical health was greatest in survivors experiencing high symptom distress and who were within the first decade post transplantation. Extended treatment with systemic immunosuppressive therapy also predicted inferior physical health. These findings suggest that patient-centered outcomes are preserved relative to normative values and are generally stable after allogeneic HSCT, although survivors with persistent symptoms and those receiving systemic immunosuppression experience impairments in health status and HRQL.

Function, adjustment, quality of life and symptoms (FAQS) in allogeneic hematopoietic stem cell transplantation (HSCT) survivors: a study protocol.

BACKGROUND: The population of survivors following allogeneic HSCT continues to increase, and yet their experiences of recovery and long-term survivorship have not been fully characterized. This paper presents a study protocol examining over time the functional status, psychosocial adjustment, health-related quality of life, and symptom experience of survivors who have undergone allogeneic transplantation. The aims of the study are to: 1) explore the patterns of change in these health outcomes during the survivorship phase; 2) characterize subgroups of survivors experiencing adverse outcomes; and 3) examine relationships among outcomes and demographic and clinical factors (such as age, graft-versus-host disease (GVHD), and disease relapse). METHODS: In this longitudinal observational study, adults who survive a minimum of 3 years from date of allogeneic transplantation complete a series of questionnaires annually. Demographic and clinical data are collected along with a series of patient-reported outcome measures, specifically: 1) Medical Outcomes Study SF- 36; 2) Functional Assessment of Chronic Illness Therapy (FACIT) - General, 3) FACIT-Fatigue; 4) FACIT- Spiritual; 5) Psychosocial Adjustment to Illness Scale; 6) Rotterdam Symptom Checklist-Revised; and 7) Pittsburgh Sleep Quality Index. CONCLUSIONS: This study will provide multidimensional patient-reported outcomes data to expand the understanding of the survivorship experience across the trajectory of allogeneic transplantation recovery. There are a number of inherent challenges in recruiting and retaining a diverse and representative sample of long-term transplant survivors. Study results will contribute to an understanding of outcomes experienced by transplant survivors, including those with chronic GVHD, malignant disease relapse, and other late effects following allogeneic transplantation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00128960.

An individualized dyadic problem-solving education intervention for patients and family caregivers during allogeneic hematopoietic stem cell transplantation: a feasibility study.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) generates multiple problems that vary in complexity and create significant distress for both patients and their caregivers. Interventions that address patient and family caregiver distress during allogeneic hematopoietic stem cell transplantation (HSCT) have not been tested. OBJECTIVE: To evaluate the feasibility of conducting an individualized dyadic problem-solving education (PSE) intervention during HSCT and estimate a preliminary effect size on problem-solving skills and distress. METHODS: The PSE intervention consisted of 4 sessions of the Prepared Family Caregiver PSE model. Data were collected with an interventionist log, subject interviews and standardized questionnaires. RESULTS: Of the 34 adult dyads screened, 24 were ineligible primarily because of being non-English-speaking (n = 11) and inconsistent caregivers (n = 10). Ten dyads (n = 20) were enrolled, and 8 dyads (n = 16) completed the intervention. Of the 31 sessions, 29 were completed (94%). Worsening patient condition was the primary reason for sessions to be incomplete. Patients attended 90% of the sessions; caregivers attended 74%. Reasons for missed sessions included patient symptom distress and limited caregiver availability. Dyads reported being very satisfied (mean, 4.8 [SD, 1.8]; range, 1-5), stating "an opportunity to talk" and "creative thinking" were most beneficial. CONCLUSION: Results suggest that dyads can participate in PSE during HSCT and view it as beneficial. Participants identified the active process of solving problems as helpful. IMPLICATIONS FOR PRACTICE: Targeted interventions that promote effective, meaningful behaviors are needed to guide patients and caregivers through HSCT. Future research recommendations include testing a version of PSE with fewer sessions, including spousal and nonspousal caregivers and those who are non-English speaking.

The effect of weather on headache.

OBJECTIVES: To assess headache patients' beliefs about how strongly weather affects their headaches; To objectively investigate the influence of multiple weather variables on headache. DESIGN AND METHODS: Our sample consisted of 77 migraineurs seen in a headache clinic, who provided headache calendars for a period ranging from 2 to 24 months. Our study was divided into two phases. First, each patient was given a questionnaire assessing their beliefs about how strongly (if so) weather affected their headaches. Second, weather data were collected from the National Weather Service, from three reporting stations central to the residences of the study participants. Analysis was performed on 43 variables to generate three meteorological factors. Linear regression was used to assess the relationship between headache and these three factors. Factor 1 represents a function of absolute temperature and humidity. Factor 2 represents a changing weather pattern. Factor 3 represents barometric pressure. RESULTS: Of the 77 subjects in the study, 39 (50.6%), were found to be sensitive to weather, but 48 (62.3%) thought they were sensitive to weather conditions (P < 0.05). Thirty (38.9%) were sensitive to one weather factor and 9 (11.7%) to two factors. Twenty-six (33.7%) were sensitive to factor 1; 11 (14.3%) to factor 2; 10 (12.9%) to factor 3. CONCLUSIONS: Our study supports the influence of weather variables on headache. We showed that patients are susceptible to multiple weather variables and that more patients thought weather was a trigger than was the case.