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Ionis Pharmaceuticals, Inc. Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that markedly increases plasma triglycerides (TG), causing pancreatitis, abdominal pain, and other symptoms that profoundly impact patients' quality of life. In a randomized, placebo-controlled phase 3 study (Balance; NCT04568434), olezarsen significantly reduced TGs among adults with FCS. To further explore the FCS patient experience during olezarsen treatment, including perceptions of meaningful changes in FCS symptoms and impacts. Patients with FCS (US, Canada, Spain, Italy) continuing olezarsen treatment in an open-label extension (OLE) of the Balance study participated in 1-hour semistructured qualitative interviews via telephone. Thematic analysis was conducted. Eighteen of 60 OLE participants completed interviews (10 female; 55.6%); mean age at interview was 43.5 (range, 23-73) years. (See Table 1 for participant characteristics.) When interviewed, participants randomized to active drug in Balance had received olezarsen for 67-113 weeks, whereas participants randomized to placebo had received olezarsen for 16-47 weeks. Seventeen of 18 participants reported a history of pancreatitis, including 14 with pancreatitis events in the 10 years prior to enrollment in the Balance study (13/14 requiring hospitalization). Moreover, all participants reported experiencing at least 1 FCS-related symptom prior to enrollment, such as abdominal pain (n=17; 94.4%), physical fatigue (n=12; 66.7%), diarrhea (n=10; 55.6%), vomiting (n=9; 50.0%), nausea (n=6, 33.3%), and difficulty thinking (n=5, 27.8%). Fifteen participants reported being symptomatic in the absence of pancreatitis, most commonly experiencing abdominal pain (n=12). All participants reported FCS-related impacts, including dietary restrictions (n=18; 100%), mood/emotions (n=17; 94.4%), hospitalizations (n=14; 77.8%), and social activities (n=14; 77.8). Participant feedback on treatment-related improvements was based on their experiences and belief of starting olezarsen, either within Balance or OLE. Fifteen of 18 participants (83.3%) reported improvements, including reductions in FCS-related symptoms (abdominal pain [n=14/17; 82.4%], physical fatigue [n=7/12; 58.3%], diarrhea [n=6/10; 60.0%], vomiting [n=7/8; 87.5%], nausea [n=3/5; 60.0%], difficulty thinking [n=3/5; 60.0%]) and impacts (relationships [n=6/7; 85.7.0%], hospital admittances [n=11/14; 78.6%], finances [n=3/4; 75.0%], mood/emotions [n=12/17; 70.6%]). All 14 participants with pancreatitis events in the past 10 years reported pancreatitis-related improvements, including 11 (78.6%) with no pancreatitis events and 3 (21.4%) with less frequent and/or less severe events since they believed they started olezarsen treatment. Overall, most participants (15/18; 83.3%) reported meaningful improvements and indicated they were satisfied with olezarsen treatment. Results of this qualitative study both underscore the significant burden of FCS and support the efficacy of olezarsen from the patient perspective. [ABSTRACT FROM AUTHOR]

Background: Treatment of schizophrenia and major depressive disorder (MDD) with atypical antipsychotics (AAPs) show improved efficacy and reduced side effect burden compared with older antipsychotic medications. However, a risk of treatment-emergent adverse events (TEAEs) remains. TEAEs are hard to quantify and perspectives on the importance of TEAEs differ across patients and between patients and physicians. The current study is a qualitative assessment that investigates TEAEs of AAPs from both patient and physician perspectives to provide better understanding of the occurrence and burden of TEAEs associated with these medications. Methods: Focus groups comprised of patients with MDD and interviews with patients with schizophrenia were conducted at two qualitative research facilities, along with a physician focus group at one of the facilities. Information collected from patients included an exhaustive list of TEAEs experienced, and the frequency and level of bother of each TEAE; from psychiatrists, information included an exhaustive list of TEAEs based on personal observations and patient report, frequency of TEAEs, clinically important TEAEs, and levels of patient-perceived bother. Standard qualitative analysis methods were used to identify, quantify, characterize, and summarize patterns found in the data collected. Results: A total of 42 patients (25 with MDD and 17 with schizophrenia) and 4 psychiatrists participated in the study. TEAEs reported as bothersome across both patients groups included cognitive issues, weight gain and/or increased appetite, low energy, extrapyramidal symptoms (EPS), and need to sleep/excessive sleep/excessive sleepiness. TEAEs considered more bothersome by patients with schizophrenia were weight gain, low energy, EPS, mental anxiety, and increased positive symptoms; those considered more bothersome by patients with MDD were cognitive issues, somnolence/sedation, and flat/restricted affect. TEAEs considered most clinically important by psychiatrists included metabolic syndrome, weight gain, neutropenia, hyperglycemia, and QT prolongation; those TEAEs considered most bothersome to patients from physicians' perspectives included weight gain, reduced sexual desire or performance, EPS, akathisia, and hormonal issues. Conclusions: The wide range of TEAEs that are both frequent and bothersome and the variation in perceived burden according to diagnosis highlight the need for a tailored TEAE-awareness approach when choosing an AAP. [ABSTRACT FROM AUTHOR]

Background: Moderate to severe plaque psoriasis (with or without psoriatic arthritis) places significant burden on patients’ lives.Objective: Explore and document patients’ experiences of living with psoriasis, including symptoms, treatments, impact on daily lives and patient-reported functioning.Methods: In a US-based, non-interventional study, narrative interviews were conducted at baseline and again within 16 weeks. In interviews, patients with moderate to severe psoriasis indicated symptoms, ranked symptoms according to level of bother and indicated areas of their lives affected by psoriasis. Transcripts of interviews were coded for themes. Measurements of psoriasis severity including BSA, PGA and PASI were recorded.Results: Symptoms reported most frequently included flaking/scaling (non-scalp areas), itching/scratching and rash, while the most bothersome symptoms were itching/scratching, flaking/scaling (non-scalp areas) and skin pain. Frequently reported impact areas were social and emotional.Conclusion: Broad-reaching interviews with patients with psoriasis show that these patients suffer in many aspects of their lives and in ways not indicated by typical psoriasis severity measures. Patients with psoriatic arthritis reported symptoms and disease-related complications at higher rates than those without arthritis. Physicians’ explorations of the effect of psoriasis on patients’ life events could aid in managing these patients. [ABSTRACT FROM AUTHOR]

Objective The office time required for primary care physicians (PCPs) to diagnose, treat and manage fibromyalgia (FM) patients can be extensive. The study objective was to determine if PCPs can positively impact practice economics by requiring fewer patient visits and less office time, while still achieving an acceptable quality of life, as reported by the physician. Study design Survey of PCPs who diagnose, manage and treat FM patients. Methods Surveys were administered to US private practice PCPs, obtaining information on the number of office visits, and time spent with FM patients. PCPs were allotted into two groups: FM-efficient (FME; n = 40) and FM usual care (FMUC; n = 54), based on their reported ability to achieve an acceptable quality of life for ≥50% of their FM patients in less than four office visits post FM diagnosis. An economic model estimated the monetary value of each PCP cohorts' time spent with a newly diagnosed FM patient over a 2-year timeframe. Results Significant office time cost differences across 2 years exist between FME PCPs and FMUC PCPs ($840 vs. $1117, P < 0.05). FME PCPs had a significantly lower cost of scheduled time to confirm diagnosis ($243 vs. $339, P < 0.05) and time to find right treatment ($264 vs. $365, P < 0.05) than FMUC PCPs. Both groups incurred costs related to excess visit time, but it was less for FME PCPs ($119, 29 minutes) than FMUC PCPs ($182, 44 minutes, P < 0.01), driven by quicker diagnosis confirmation ( P < 0.01) and treatment initiation ( P < 0.01). Conclusions Research suggests that efficient FM care delivery during diagnosis and treatment can be associated with improved practice economics. [ABSTRACT FROM AUTHOR]

Background: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder that impacts physical, emotional, social, and cognitive functioning. The FCS-Symptom and Impact Scale (FCS-SIS) patient-reported outcome (PRO) measure assesses common symptoms and impacts of FCS. This study was conducted to evaluate cross-sectional psychometric properties of the FCS-SIS and its scoring method., Methods: This multisite, cross-sectional, observational study of individuals with FCS was conducted in the United States and Canada. Participants completed a survey composed of 7 PRO measures, including the FCS-SIS, and questions about clinical characteristics and demographics. The structure of the FCS-SIS was evaluated using inter-item and item-scale correlations and internal consistency reliability. Construct, known-groups, and criterion validity were evaluated by examining associations between FCS-SIS item and composite scores and other measures included within the survey., Results: Most of the 33 participants were female (63.6%) and White (78.1%). On average, participants reported first noticing FCS symptoms at ~16 years, with abdominal pain the most frequently reported initial symptom (n=20). Participants reported 2.5 acute pancreatitis attacks on average over the past year. Average FCS-SIS symptom item scores ranged from 1.8 to 3.9 (on a 0-to-10 scale [none-to-worst-possible]) within the 24-hour recall period, with an average Symptom composite score of 2.7. The average impact item scores on the FCS-SIS ranged from 1.6 to 3.0 (on a 0-to-4 scale), with an average Impact composite score of 2.1. Inter-item correlations between the FCS-SIS Symptom items ranged from 0.32 to 0.78. Corrected item-total correlations were highly satisfactory for Impact items, ranging from 0.62 to 0.85. All a priori validity hypotheses were supported by observed correlations and score differences between known groups., Conclusion: The results of this study support the structure, reliability, and validity of the FCS-SIS, laying the psychometric groundwork for longitudinal evaluation of its utility in assessing treatment benefit in FCS clinical studies., Competing Interests: TMB and SF are full-time employees of RTI Health Solutions, an independent nonprofit research organization, which was retained by Ionis Pharmaceuticals to conduct the research which is the subject of this manuscript. Their compensation is unconnected to the studies on which they work. CK was an employee of RTI Health Solutions at the time the research was conducted. MVL, ASK, and AY are employees of Ionis Pharmaceuticals and hold shares and/or stock options in the company. The authors report no other conflicts of interest in this work., (© 2024 Brown et al.)

Background: Metachromatic leukodystrophy (MLD) is a rare disease with three forms based on the age at onset of signs and symptoms. The objective of this study was to develop a caregiver-reported clinical outcome assessment that measures impairments in physical functioning related to activities of daily living in patients with juvenile MLD., Methods: A targeted literature review and exploration of proprietary research, including a conceptual model, were conducted. Concept elicitation interviews were conducted to elicit additional concepts related to impairments in patients' physical functioning with caregivers of five individuals with juvenile MLD. Based on the research review and concept elicitation interviews, the conceptual model was updated and the Impact of Juvenile Metachromatic Leukodystrophy on Physical Activities (IMPA) scale draft items were created. Cognitive debriefing interviews were conducted with six additional caregivers to finalize the conceptual model and to refine the IMPA scale., Results: Initially, 17 potentially important concepts were identified and addressed in the draft IMPA scale. Following the cognitive debriefing interviews, 15 activities/items remained: brush teeth, comb/brush hair, bathe/shower, dress self, eat, drink, use pencil/crayon, sit upright, use toilet, get on/off toilet, walk, use stairs, get in/out of bed, get in/out of chair/wheelchair, and get in/out of vehicle. Items that did not uniquely contribute to the purpose of the instrument were removed., Conclusion: The IMPA scale, developed according to regulatory standards, provides a means of detecting changes in activities of daily living in individuals with juvenile MLD and can hence be used in future studies to measure benefits of therapeutic interventions., Competing Interests: This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki 2008 and reviewed and approved by the RTI International Institutional Review Board. Informed consent was obtained before participation.All authors approved this manuscript and provided consent for publication.The authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article. This study was conducted by RTI Health Solutions under the direction and funding of Shire Development LLC. RTI Health Solutions was contracted by Shire to design and implement this project. T.M.B., S.M., and S.E.F. are employees of RTI Health Solutions. L.S.D. is currently at Pfizer, Inc. but was employed at Shire Development LLC during the conduct of this project and is currently a shareholder of Shire stock. Shire develops and manufactures treatments for rare diseases, including metachromatic leukodystrophy. The authors have no additional financial relationships or otherwise to declare.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.