Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States.

BACKGROUND: Hereditary angioedema (HAE) with C1-inhibitor deficiency is associated with painful, potentially fatal attacks affecting subcutaneous or submucosal tissues. OBJECTIVE: To evaluate HAE burden from the patients' perspective. METHODS: This was a noninterventional survey of patients with HAE in the United States, conducted from March 17 to April 28, 2017. Patients were recruited through the US Hereditary Angioedema Association. Key eligibility criteria included the following: (1) aged 18 years and older, (2) self-reported physician diagnosis of HAE type I or II, (3) 1 or more HAE attacks or prodromal symptoms within the last year, and (4) receipt of HAE medication for an attack within the last 2 years. Descriptive analyses were conducted. RESULTS: A total of 445 patients completed the survey. Most patients (92.8%) were aged 18 to 64 years with HAE type I (78.4%) and had a positive family history (78.4%). Mean (SD) ages at symptom onset and diagnosis were 12.5 (9.1) and 20.1 (13.7) years, respectively. Most patients (78.7%) experienced an attack within the past month. The abdomen (58.0%) and extremities (46.1%) were commonly affected sites; pain (73.9%) and abdominal (57.0%) and nonabdominal (55.1%) swelling were frequently reported symptoms. Most patients (68.5%) had received or were currently receiving long-term prophylaxis. Most patients (88.8%) reported visiting allergists or immunologists, whereas 9.2% visited emergency departments or urgent care clinics. Per the Hospital Anxiety and Depression Scale, 49.9% and 24.0% of respondents had anxiety and depression, respectively. Mean Hereditary Angioedema-Quality of Life scores were generally lower with higher attack frequency. General health was "poor" or "fair" for 24.8% of patients. Mean (SD) percentage impairments were 5.9% (14.1%) for absenteeism, 23.0% (25.8%) for presenteeism, 25.4% (28.1%) for work productivity loss, and 31.8% (29.7%) for activity impairment. CONCLUSION: Despite treatment advances, patients with HAE in the United States continue to have a high burden of illness.

Evaluation of Risk-Minimization Activities for Cyproterone Acetate 2 mg/Ethinylestradiol 35 µg: A Cross-Sectional Physician Survey.

BACKGROUND: Cyproterone acetate 2 mg/ethinylestradiol 35 µg, an estrogen/progestogen treatment with anti-androgenic properties, shares a thromboembolism risk with combined hormonal contraceptives. Educational materials (i.e., direct healthcare professional communication, patient information card, prescriber checklist) were distributed to physicians to increase risk awareness. OBJECTIVE: The objective of this study was to measure physician knowledge of thromboembolism risk of cyproterone acetate 2 mg/ethinylestradiol 35 µg and ascertain whether physicians received the educational materials. METHODS: A cross-sectional web-based physician survey of recent prescribers of cyproterone acetate 2 mg/ethinylestradiol 35 µg in Austria, the Czech Republic, France, the Netherlands, and Spain was conducted. Sampling targets for physician specialty were based on country-specific prescribing patterns. Frequency of correct responses was calculated for 14 knowledge questions. RESULTS: Among 759 physician respondents (37% of obstetricians/gynecologists, 42% of general practitioners, 20% of dermatologists), 51% received one or more of three educational materials. Knowledge was highest (≥80%) for symptoms of possible deep vein thrombosis, pulmonary embolism, and cerebrovascular accident; most important risk factors for thrombosis; use in smokers; indication for moderate-to-severe acne; and understanding that cyproterone acetate 2 mg/ethinylestradiol 35 µg should not be used for contraception alone. Knowledge varied for contraindications, myocardial infarction symptoms, other risk factors for thrombosis, instructions regarding anticipated prolonged immobilization, and selected concomitant medical conditions. Knowledge was lower regarding prescribing cyproterone acetate 2 mg/ethinylestradiol 35 µg for acne only after failure of topical therapy or systemic antibiotics. Generally, knowledge did not vary by physician specialty, receipt of educational materials, number of patients prescribed cyproterone acetate 2 mg/ethinylestradiol 35 µg in the previous 3 months, and years in practice. CONCLUSIONS: Knowledge was generally high for thromboembolism risk and varied for more complex or infrequent topics.

Quantifying the importance of inhaler attributes corresponding to items in the patient satisfaction and preference questionnaire in patients using Combivent Respimat.

BACKGROUND: Physicians consider ease of use, satisfaction, and preferences when prescribing an inhaler device. These factors may impact appropriate usage and compliance. METHODS: The objectives were to quantify the relative importance of inhaler attributes in patients currently using Combivent Respimat by eliciting preferences for performance and convenience attributes assessed by items in the Patient Satisfaction and Preference Questionnaire (PASAPQ). Using a pharmacy database, 19,964 adults in the United States who filled ≥2 Combivent Respimat prescriptions were identified. Of those, 8150 patients were randomly selected to receive invitation letters. The online cross-sectional survey included the PASAPQ and best-worst scaling (BWS) questions. The PASAPQ measures satisfaction with medication attributes across two domains: performance and convenience. BWS questions asked participants to select the most and least important device attributes. A descriptive statistics analysis of the PASAPQ and a random-parameters logit model of BWS responses were conducted. RESULTS: The survey was completed by 503 participants. Most were female (57.3%), white (88.5%), and 51-70 years old (67.6%). Approximately 47% reported a chronic obstructive pulmonary disease diagnosis, 21.9% asthma, 8.2% other lung disease, and 23.1% more than one lung disease. PASAPQ scores indicated that the majority were satisfied or very satisfied; up to 20% reported being dissatisfied with Combivent Respimat. The three most important inhaler attributes were Feeling that your medicine gets into your lungs, Inhaler works reliably, and Inhaler makes inhaling your medicine easy. The most important attributes corresponded to six of seven items in the PASAPQ performance domain. CONCLUSIONS: Most participants reported satisfaction with Combivent Respimat. Performance attributes were more important than convenience attributes.

The development of a survey to measure completeness of response to migraine therapy.

OBJECTIVE: To assess the psychometric properties of a new patient-reported migraine instrument, the Completeness of Response Survey (CORS), which measures a comprehensive set of factors important to patients' decisions regarding the initiation and continuation of treatment. BACKGROUND: Traditionally, migraine treatments and the instruments used to demonstrate their efficacy have focused on the relief of headache pain. As new treatments emerge with the potential for more complete and consistent migraine relief, more comprehensive tools are needed to demonstrate these benefits. The CORS includes 2 modules, the static CORS, which comprehensively evaluates one treatment at one time point, and the comparative CORS, which provides a more global comparison between 2 treatments at one time point. Together, the 2 modules can measure unmet treatment needs and improvements over the course of a clinical study. METHODS: Data from an 8-site study comparing 147 patients' recent experiences with their current triptan therapy and 2 months of study treatment with a single-tablet formulation of sumatriptan/naproxen sodium were used to conduct a preliminary psychometric evaluation of the CORS. The study included both modules of the CORS, the Headache Impact Test, the revised Patient Perception of Migraine Questionnaire, and a migraine diary. RESULTS: The CORS response categories in both the static and comparative modules demonstrated limited floor or ceiling effects and few missing values (<3%). Inter-item correlations, principal components analysis (component loading range: 0.62 to 0.95), and high estimates of internal consistency (alpha range: 0.88 to 0.94) for each composite score supported the structure and proposed scoring algorithm for the static module. The pattern of correlations between the CORS static and comparative items and composites with the revised Patient Perception of Migraine Questionnaire items and subscales, as well as the relationships between responses to selected static CORS items and the migraine diary, supported the construct validity of the CORS. CONCLUSIONS: The CORS is capable of demonstrating advantages of more comprehensive migraine therapies over traditional therapies, which are primarily focused on the resolution of headache pain, by addressing the frequency and speed with which the most common migraine symptoms are resolved and patients' return to normal functioning. This research shows evidence for the value and utility for the CORS static and comparative items and components, and further evaluation is underway.

Development of a family functioning scale for major depressive disorder.

OBJECTIVE: To better understand depression's impact on family functioning from the perspectives of patients with major depressive disorder (MDD) and their partners; to develop and test patient and partner versions of a new self-reported measure, the Depression and Family Functioning Scale (DFFS), for use in clinical trials. METHODS: Concept elicitation interviews were conducted with 32 adults with clinician-diagnosed moderate-to-severe MDD and their respective partners. Twenty-six items were drafted to address relevant aspects of family functioning and were then tested and refined through two iterative sets of cognitive debriefing interviews, each conducted by the same pair of highly experienced researchers, including a licensed clinical psychologist. RESULTS: Depression negatively affects family functioning through poorer communication, increased conflicts, decreased family interaction, and decreased intimacy. No existing instrument measured all domains of interest, or had been rigorously developed and psychometrically validated in the target populations. The draft DFFS items generally tested well and only minor modifications were made to the items after the second set of interviews. Both patients and partners indicated that the final set of 15 DFFS items addresses all concepts of importance. CONCLUSIONS: The DFFS evaluates the impact of depression on family functioning and has the potential to provide important information that can facilitate a more comprehensive evaluation of new treatments in clinical trial settings. Although MDD severity was not confirmed with a standardized interview, in clinical practice in the US, MDD is generally not diagnosed with the use of a structured clinical interview or clinician-administered tool. In the current study, depression severity had little (if any) impact on the specific concepts elicited as being important to family functioning. In fact, patients with milder depression had more insight and were able to better articulate changes in family functioning with treatment.

Effect of lamotrigine on cognitive complaints in patients with bipolar I disorder.

BACKGROUND: This analysis describes the effects of bipolar I disorder on self-reported neurocognitive measures and remediation of these deficits with lamotrigine therapy. METHOD: Data were derived from 2 clinical trials designed to assess the efficacy of lamotrigine as maintenance therapy for recently manic (N = 349) or depressed (N = 966) patients (DSM-IV criteria). During the 8- to 16-week open stabilization phase, patients received lamotrigine as monotherapy or as adjunctive therapy (target dose = 200 mg/day, minimum dose = 100 mg/day) while other psychotropic drugs were discontinued. The Medical Outcomes Study Cognitive Scale (MOS-Cog) and the AB-Neurological Assessment Scale (AB-NAS) were used to measure cognitive functioning at baseline and at the end of the open-label phase. To examine the relationship between depressive and manic symptomatology, initiation of lamotrigine, and cognitive functioning, correlational analyses and analyses of covariance were conducted. RESULTS: Bipolar patients in both trials had significant cognitive impairment; however, it was much greater in index episode depressed bipolar patients compared with index episode manic patients. In both studies, substitution of lamotrigine for other psychotropic medications significantly improved the mean scores from baseline to the end of the open-label phase on the MOS-Cog and the AB-NAS (p < .0001). Among patients who took lamotrigine as monotherapy, the mean MOS-Cog score also improved significantly versus baseline (+32.2, or 81%, for depressed patients, p < .0001; and +19.9, or 35%, for manic patients, p < .0001). Mean AB-NAS scores (-19.7, or -55%, for depressed patients, p < .0001; and -7.2, or -32%, for manic patients, p = .0062) showed similar improvement. Cognitive impairment was significantly correlated with depression symptom severity based on Hamilton Rating Scale for Depression scores (p < .0001). After controlling for change in mood, age, gender, baseline score, duration of illness, and duration of use of other psychotropics, a significant improvement in cognition was observed during the open-label phase when lamotrigine was used as monotherapy/adjunctive therapy. CONCLUSION: Treatment with lamotrigine as monotherapy and as adjunctive therapy was associated with improved cognitive functioning and reduced neurocognitive side effects, regardless of index mood polarity.

Quality of life in patients with bipolar I depression: data from 920 patients.

OBJECTIVE: To determine the impact of acute depression on quality of life (QOL) in patients with bipolar I disorder and to compare these results with published data on QOL in patients with unipolar depression. METHODS: Quality of life was assessed using the SF-36 in bipolar patients (n = 958) who had recently experienced an episode of acute bipolar depression and participated in a large randomized, double-blind, safety and efficacy trial. Seven studies that included SF-36 data from patients with unipolar depression were identified in the published literature and descriptive comparisons of SF-36 scores were made between the unipolar depression trials and this bipolar depression trial. RESULTS: There were 920 patients who completed the SF-36. Mean transformed scores, which could range from 0 to 100, were very low in bipolar depressed patients for the role-physical (36.7), vitality (22.4), social functioning (29.9), role-emotion (11.4), and mental health (31.0) subscales. Mean SF-36 scores for all subscales were significantly and inversely correlated (p < 0.0001) with the HAM-D indicating that patients with milder depressive symptoms had better QOL. Further, the mean SF-36 scores for the bipolar sample were consistently lower compared with published data on QOL in unipolar depression on four of the eight subscales: general health; social functioning; role-physical, and role-emotional. CONCLUSIONS: While both unipolar and bipolar depression have serious detrimental effects on patient QOL, our results suggest that some aspects of QOL may be worse in bipolar depression.