Peanut allergy burden survey: Factors associated with health-related quality of life in adolescents.

BACKGROUND: Patients with peanut allergy (PA) experience significant burden of illness, which impacts health-related quality of life (HRQoL), particularly in adolescence. There is a paucity of research evaluating drivers of HRQoL scores. METHODS: A prospective, online survey of adolescents with self-reported, provider-diagnosed PA completed from November 2018 to January 2019 was used to explore drivers of the real-world impact of PA on HRQoL using the Pediatric Quality of Life Inventory 4.0 (PedsQL) and other measures. Univariate and multivariate analyses were used to identify potential factors associated with PedsQL scores and to understand the level of association. RESULTS: A total of 102 adolescents were included. The final model included 10 variables: race, reported strict peanut avoidance, satisfaction with prophylaxis, moderate-to-severe reaction within the past 12 months, touching peanut as cause of most severe reaction, fear of reaction, age, gender, comorbidities, and daily life limitations. In total, three items were shown to be strong predictors of the PedsQL total score including cause of severe reaction was touching peanut (yes), level of agreement with avoiding peanut (completely agree), and satisfaction with prophylaxis (not very much/not at all). CONCLUSIONS: There is substantial heterogeneity in the impact of the burden of PA on PedsQL scores across patients. This indicates the importance of shared and individualized decision making for PA management to optimize outcomes and improve HRQoL.

Perspectives on nonmedical switching and the COVID-19 pandemic: a narrative review.

OBJECTIVES: Nonmedical switching (NMS) is a change in a patient's treatment regimen for reasons other than lack of efficacy, intolerance, adverse effects, or poor adherence. We describe the impact of NMS on patients, health care workers, and health systems, focusing on NMS to in-class biologic alternatives in US patients with chronic, immune-mediated rheumatic and dermatologic conditions. Additionally, we evaluate the ways in which the COVID-19 pandemic may exacerbate the physical, psychological, and economic impacts of NMS. STUDY DESIGN: Narrative review. METHODS: We performed a search of MEDLINE's PubMed database from October 2015 to October 2020, with a repeat search in October 2021. Search terms included relevant keywords pertaining to NMS, biologics, and disease areas. Results were supplemented by a search of key congress abstracts from 2015 to 2021 and a targeted internet search. RESULTS: NMS increases medication abandonment, errors, and adverse effects, and it can lead to longer patient visits, increased follow-up visits, additional laboratory tests and procedures, and greater overall health care resource utilization (HCRU). The increased HCRU associated with NMS increases patients' financial burden due to additional co-pays and out-of-pocket costs. CONCLUSIONS: The decision to switch treatments should result from shared decision-making between health care providers (HCPs) and patients to achieve the best clinical outcomes and optimal HCRU. The issues related to NMS may be compounded by the financial and psychosocial stress on HCPs and patients created by the COVID-19 pandemic. HCPs should advocate for continuous patient treatment and be familiar with continuity of care legislation, appeals processes, and manufacturer assistance programs.

Health care utilization and costs associated with functional status in patients with psoriatic arthritis.

BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) has been validated and widely used in psoriatic arthritis (PsA) clinical trials for the assessment of patient functional status. Significant improvements in the HAQ-DI have been reported in response to therapeutic interventions; however, few US studies have evaluated the economic impact of functional disability in patients with PsA. OBJECTIVE: To evaluate the association of functional status with health care resource utilization (HCRU) and total health care costs in US patients diagnosed with PsA. METHODS: This retrospective study included adult patients with PsA enrolled in FORWARD between July 2009 and June 2019 who completed 1 or more HAQ-DI questionnaires between January 2010 and December 2019. Patient demographics, clinical characteristics, and patient-reported outcomes were collected from the most recent questionnaire. HCRU and total health care costs (2019 US dollars) for all hospitalizations, emergency department (ED) visits, outpatient visits, diagnostic tests, and procedures were assessed for the 6 months prior to survey completion. Negative binomial regression models (HCRU outcomes) and generalized linear models with γ distribution and log-link function (cost outcomes) were used to assess the relationship between HAQ-DI and HCRU and cost outcomes, respectively. RESULTS: A total of 828 patients with PsA who completed HAQ-DI questionnaires were included. The mean (SD) age was 58.5 (13.5) years, 72.3% were female, and 92.3% were White. The mean (SD) disease duration was 17.5 (12.4) years, and the mean (SD) HAQ-DI score at the time of the patients' most recent questionnaire was 0.9 (0.7). More severe functional disability, measured by higher HAQ-DI score, was significantly associated with increased risk (incident rate ratio [95% CI]) of hospitalizations (1.68 [1.11-2.55]), ED visits (2.09 [1.47-2.96]), outpatient visits (1.14 [1.05-1.24]), and diagnostic tests (1.42 [1.16-1.74]). There was also a significant positive association between greater HAQ-DI score and increased total annualized health care costs (incremental amount [95% CI], 1.13 [1.03-1.23]) and medical costs (1.38 [1.13-1.69]), but there was no significant association found with pharmacy costs. Total adjusted average patient medical costs increased with increasing HAQ-DI score. CONCLUSIONS: Among patients with PsA enrolled in FORWARD, more functional disability-as measured by higher HAQ-DI scores-was associated with greater HCRU and increased total health care costs. These results suggest that improving functional status in patients with PsA may reduce economic burden for health care payers and systems. DISCLOSURES: Dr Ogdie has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, CorEvitas (formerly Corrona), Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, National Psoriasis Foundation, Pfizer (University of Pennsylvania), Amgen (FORWARD), and Novartis (FORWARD). Dr Hwang has received consulting fees from Novartis and UCB and has received grant support (5KL2TR003168-03) from the University of Texas Health Science Center at Houston Center of Clinical and Translational Sciences KL2 program. Drs Veeranki and Shafrin were employees of PRECISIONheor at the time of this analysis. Ms Portelli and Mr Sison are employees of PRECISIONheor. Ms Pedro has nothing to disclose. Dr Hass is an employee of H. E. Outcomes, providing consulting services to Novartis. Dr Hur was an employee of Novartis at the time of this analysis. Dr Kim was a postdoctoral fellow at the University of Texas at Austin and Baylor Scott and White Health, providing services to Novartis at the time of this analysis. Dr Yi is an employee of Novartis. Dr Michaud received grant funding from the Rheumatology Research Foundation at the time of this analysis. This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Comparison of Clinical Manifestations in Rheumatoid Arthritis vs. Spondyloarthritis: A Systematic Literature Review.

INTRODUCTION: Misclassification of spondyloarthritis (SpA) as rheumatoid arthritis (RA) may lead to delayed SpA diagnosis and suboptimal therapeutic outcomes. Here, we evaluate the literature on clinical manifestations in patients with SpA and RA, particularly seronegative RA, to understand the potential overlap, distinctions, and most reliable approaches to accurate diagnosis. METHODS: In this systematic literature review, conducted according to PRISMA guidelines, we searched key biomedical databases for English-language publications of original research articles (up to July 23, 2020) and rheumatology conference abstracts (January 1, 2018-July 31, 2020) reporting key SpA clinical presentations in patients with SpA or RA. Publications were assessed for eligibility by two independent reviewers; discrepancies were resolved by a third. Studies were evaluated for publication quality using the Downs and Black checklist. RESULTS: Of 4712 records retrieved, 79 met the inclusion criteria and were included in the analysis. Of these, 54 included study populations with SpA and RA, and 25 with seropositive and/or seronegative RA. Entheseal abnormalities were more frequently reported among patients with SpA than RA and with seronegative vs. seropositive RA. Psoriasis, nail psoriasis, and dactylitis were exclusively seen in SpA vs. RA. In most publications (70 of 79), advanced imaging techniques allowed for more accurate distinction between SpA and RA. Overlapping clinical characteristics occur in SpA and RA, including inflammation and destruction of joints, pain, diminished functional ability, and increased risk for comorbidities. However, of 54 studies comparing SpA and RA populations, only seven concluded that no distinction can be made based on the SpA manifestations and outcomes examined. CONCLUSIONS: Typical SpA-related clinical symptoms and signs were observed in patients with RA, suggesting that misclassification could occur. Availability of advanced imaging modalities may allow for more prompt and comprehensive evaluation of peripheral manifestations in SpA and RA, reducing misclassification and delayed diagnosis.

Spondyloarthritis (SpA) is a group of chronic, inflammatory diseases that includes axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), in addition to other peripheral forms of SpA. AxSpA primarily affects the spine and can cause chronic back pain. PsA occurs in patients with the skin condition psoriasis and patients often experience symptoms including joint pain, stiffness, and swelling. Quick and accurate diagnosis of SpA is necessary to prevent joint damage and physical limitations. Rheumatoid arthritis (RA) is characterized by pain, swelling, and stiffness in multiple joints, and delayed diagnosis and treatment can have lasting effects. However, many patients with SpA and RA who initially seek medical care often experience delayed diagnoses. This study evaluated the literature on symptoms in patients with SpA and RA, particularly patients with RA without antibodies typically associated with the disease, to understand the potential overlap, differences, and most reliable ways to accurately diagnose patients. Data from 79 records were included in the analysis, 54 of which included study populations with SpA and RA. Skin and nail psoriasis, as well as swelling of the fingers and toes, was only seen in patients with SpA. Most studies showed that enhanced imaging allowed for distinguishing between SpA and RA. This study showed that typical signs and symptoms of SpA, including inflammation and joint pain, could also be seen in patients with RA, which suggests that challenges exist for accurately identifying SpA. This highlights the importance of advanced imaging to diagnose and treat patients with SpA in a timely manner.

Medical and nursing home costs: From cognitively unimpaired through dementia.

INTRODUCTION: Efforts to model the cost-effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing-home (NH) costs. METHODS: A stratified-random sample of Olmsted County, MN, residents ages 70-89 years (N = 3545), well-characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider-linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH-use intensity (NH days/follow-up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between-category mean-annual cost differences were adjusted for patient characteristics and follow-up days. RESULTS: Costs/follow-up day distributions differed significantly across cognitive categories. Mean costs/follow-up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted-between-category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired. DISCUSSION: Cost-effectiveness for managing/modifying both MCI and dementia should consider end-of-life costs and NH-use intensity. Results can help inform cost-effectiveness models, predict future-care needs, and aid decision-making by individuals/providers/payers/policymakers.

The Peanut Allergy Burden Study: Real-world impact of peanut allergy on resource utilization and productivity.

BACKGROUND: There is limited research demonstrating the real-world economic burden of peanut allergy (PA) in the United States. The Peanut Allergy Burden Study (PABS) is a cross-sectional quantitative survey designed to determine the real-world experience of patients and caregivers with PA. The objective of the study was to understand the real-world utilization of PA-related healthcare resources and the impact of PA on productivity. METHODS: Participants completed an online survey to examine the real-world 12-month and lifetime healthcare utilization and past week productivity impact of PA in children (as reported by caregiver proxy), adolescents with PA, adults with PA, and caregivers of children with PA. RESULTS: Healthcare resource use over the past 12 months was frequent for adults (n = 153), adolescents (n = 102), and children (as reported by caregivers) (n = 382) with PA. Patients and caregivers reported the following rates of PA-related utilization in the past 12 months: at least 3 regular allergist appointments (28.8%-39.3%), unscheduled allergist appointments (15.6%-18.3%), general practitioner appointments (16.7%-24.2%), over-the-counter (OTC) medication usage (28.5%-35.7%), and epinephrine autoinjector usage (17.7%-26.2%). Additionally, over half of patients and caregivers reported ≥1 PA-related emergency department (ED)/urgent care visit (57.5%-59.9%), overnight hospital admission (36.3%-47.4%), IV epinephrine use (37.2%-52.3%), or intubation (26.2%-39.8%) over the past 12 months for PA. Healthcare resource use was high among all groups. Regarding productivity, PA significantly impacted household work, schoolwork, and employed work for patients and caregivers. PA-related reactions also impacted school attendance of children with PA. CONCLUSION: Many healthcare resources were utilized by patients with PA and there was a loss of productivity associated with PA for patients and caregivers. New treatments to prevent or lower the risk of PA reactions could potentially help reduce healthcare resource utilization and PA-related productivity loss among patients and their families, particularly for patients for whom avoidance as a treatment strategy has not been reliable.

The Peanut Allergy Burden Study: Impact on the quality of life of patients and caregivers.

BACKGROUND: Peanut allergy (PA) places significant burden on peanut-allergic individuals and their families, yet limited research in the United States has quantitatively examined the impact on peanut-allergic individuals and their families' health-related quality of life (HRQoL). The Peanut Allergy Burden Study (PABS) aimed to quantify the impact of PA on the general and disease-specific HRQoL of children, adolescents, and adults with PA, as well as caregivers of children with PA. METHODS: A cross-sectional survey design was employed to examine the real-world impact of PA in children, adolescents, and adults with PA, and caregivers of children with PA. RESULTS: Of 153 adult patients, 102 adolescents, and 382 caregivers of peanut-allergic children (n = 382), 6.8% and 24.8% of participants indicated being dissatisfied or somewhat dissatisfied, respectively, with current approaches to avoid or prevent PA reactions. Approximately two-thirds of patients and caregivers indicated that PA interferes at least somewhat with daily living. In terms of general HRQoL, adolescents, adult patients, and caregivers indicated that mental/psychosocial health was more problematic than physical health. PA patients and caregivers indicated worse HRQoL in all domains compared to healthy samples, and worse overall HRQoL, psychosocial, emotional, and social functioning than a sample of chronically ill patients. Results from the allergy-specific HRQoL measures showed that adolescents experienced greater impairment in overall HRQoL due to PA and in allergen avoidance and dietary restriction than adults. CONCLUSION: PA negatively affects the general and PA-specific HRQoL of both patients and caregivers. The high emotional and psychosocial burden, in particular, demonstrates significant unmet need for patients with PA and their caregivers. Future work on treatment and preventive options to improve HRQoL for PA patients, particularly adolescents and their families, is needed.

Patient Preferences for Device-Aided Treatments Indicated for Advanced Parkinson Disease.

BACKGROUND: Effective treatment for advanced Parkinson disease (PD) uncontrolled with oral medication includes device-aided therapies such as deep brain stimulation (DBS) and continuous levodopa-carbidopa infusion to the duodenum via a portable pump. OBJECTIVE: Our objective was to quantify patient preferences for attributes of these device-aided treatments. METHODS: We administered a Web-enabled survey to 401 patients in the United States. A discrete-choice experiment (DCE) was used to evaluate patients' willingness to accept tradeoffs among efficacy, tolerability, and convenience of alternative treatments. DCE data were analyzed using random-parameters logit. Best-worst scaling (BWS) was used to elicit the relative importance of device-specific attributes. Conditional logit was used to analyze the BWS data. We tested for differences in preferences among subgroups of patients. RESULTS: Improving ability to think clearly was twice as important as a 6-hour-per-day improvement in control of movement symptoms. After controlling for efficacy, treatment delivered via portable infusion pump was preferred over DBS, and both devices were preferred to oral therapy with poor symptom control. Patients were most concerned about device attributes relating to risk of stroke, difficulty thinking, and neurosurgery. Avoiding surgery to insert a wire in the brain was more important than avoiding surgery to insert a tube into the small intestine. Some differences in preferences among subgroups were statistically, but not qualitatively, significant. CONCLUSIONS: This study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions.

Nursing Home Use Across The Spectrum of Cognitive Decline: Merging Mayo Clinic Study of Aging With CMS MDS Assessments.

BACKGROUND/OBJECTIVES: Objective, complete estimates of nursing home (NH) use across the spectrum of cognitive decline are needed to help predict future care needs and inform economic models constructed to assess interventions to reduce care needs. DESIGN: Retrospective longitudinal study. SETTING: Olmsted County, MN. PARTICIPANTS: Mayo Clinic Study of Aging participants assessed as cognitively normal (CN), mild cognitive impairment (MCI), previously unrecognized dementia, or prevalent dementia (age = 70-89 years; N = 3,545). MEASUREMENTS: Participants were followed in Centers for Medicare and Medicaid Services (CMS) Minimum Data Set (MDS) NH records and in Rochester Epidemiology Project provider-linked medical records for 1-year after assessment of cognition for days of observation, NH use (yes/no), NH days, NH days/days of observation, and mortality. RESULTS: In the year after cognition was assessed, for persons categorized as CN, MCI, previously unrecognized dementia, and prevalent dementia respectively, the percentages who died were 1.0%, 2.6%, 4.2%, 21%; the percentages with any NH use were 3.8%, 8.7%, 19%, 40%; for persons with any NH use, median NH days were 27, 38, 120, 305, and median percentages of NH days/days of observation were 7.8%, 12%, 33%, 100%. The year after assessment, among persons with prevalent dementia and any NH use, >50% were a NH resident all days of observation. Pairwise comparisons revealed that each increase in cognitive impairment category exhibited significantly higher proportions with any NH use. One-year mortality was especially high for persons with prevalent dementia and any NH use (30% vs 13% for those with no NH use); 58% of all deaths among persons with prevalent dementia occurred while a NH resident. CONCLUSIONS: Findings suggest reductions in NH use could result from quality alternatives to NH admission, both among persons with MCI and persons with dementia, together with suitable options for end-of-life care among persons with prevalent dementia.

Measuring treatment satisfaction in MS: Is the Treatment Satisfaction Questionnaire for Medication fit for purpose?

BACKGROUND: The Treatment Satisfaction Questionnaire for Medication (TSQM) was designed to assess patient treatment satisfaction in chronic diseases. Its performance has not been examined in multiple sclerosis (MS). The 14 items of the TSQM cover four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. OBJECTIVE: To evaluate performance of the TSQM in patients with relapsing MS, using data collected from the TENERE study (NCT00883337), in which 324 patients received oral teriflunomide or subcutaneous interferon beta-1a for ⩾48 weeks. METHODS: Five measurement properties were examined using traditional psychometric methods: data completeness, scale-to-sample targeting, scaling assumptions, reliability (including test-retest), and construct validity (internal: item-level scaling success, confirmatory factor analysis, and exploratory factor analysis; external: convergence, discrimination, and group differences). RESULTS: There were few (<2%) missing item data; domain scores could be computed for all patients. Score distributions were skewed toward higher satisfaction; two domains had marked ceiling effects. Scaling assumptions were supported. Internal consistency reliability was high (Cronbach's α > 0.90). Internal validity tests supported item groupings. Correlations supported convergent and discriminant construct validity; hypothesis testing supported group differences validity. CONCLUSION: This investigation found the TSQM to be a useful tool, exhibiting good psychometric measurement properties in patients with relapsing MS in the TENERE study.

Comparing outcomes from clinical studies of oral disease-modifying therapies (dimethyl fumarate, fingolimod, and teriflunomide) in relapsing MS: Assessing absolute differences using a number needed to treat analysis.

Dimethyl fumarate (DMF), fingolimod, and teriflunomide are oral disease-modifying therapies (DMTs) indicated for the treatment of relapsing-remitting multiple sclerosis. Despite well-established limitations of cross-trial comparisons, DMTs are still frequently compared in terms of relative reductions in specific endpoints, most commonly annualized relapse rate. Consideration of absolute risk reduction and number needed to treat (NNT) provides an alternative approach to assess the magnitude of treatment effect and can provide valuable additional information on therapeutic gain. Using data from pivotal studies of DMF (DEFINE, NCT00420212; CONFIRM, NCT00451451), fingolimod (FREEDOMS, NCT00289978; FREEDOMS II, NCT00355134), and teriflunomide (TEMSO, NCT00134563; TOWER, NCT00751881), we calculated NNTs to prevent any relapse, more severe relapses (such as those leading to hospitalization or requiring intravenous corticosteroids), and disability worsening. Higher relative reductions were reported for DMF and fingolimod vs placebo on overall relapse and relapses requiring intravenous corticosteroids in both individual and pooled studies (pooled data unavailable for fingolimod). However, NNTs for each outcome were similar for DMF and teriflunomide, with marginally lower NNTs observed with fingolimod. By contrast, for relapses requiring hospitalization, relative reductions were higher and NNTs were substantially lower for teriflunomide compared with DMF. For fingolimod, there were inconsistent outcomes between the two studies for relapses requiring hospitalization; thus, comparative conclusions against DMF or teriflunomide cannot be clearly established. The risk of disability worsening was significantly reduced in both teriflunomide studies, but only in a single study for DMF (DEFINE) and fingolimod (FREEDOMS). NNTs to prevent one patient from experiencing disability worsening were similar in DEFINE, FREEDOMS, and TEMSO and TOWER but were higher in CONFIRM and FREEDOMS II. This NNT analysis demonstrates broadly comparable effects for DMF, fingolimod, and teriflunomide across key clinical outcomes. These observations are clinically relevant and may help to inform treatment decisions by providing additional information on therapeutic gain beyond informal assessments of relative reductions alone.

Direct medical costs and source of cost differences across the spectrum of cognitive decline: a population-based study.

BACKGROUND: Objective cost estimates and source of cost differences are needed across the spectrum of cognition, including cognitively normal (CN), mild cognitive impairment (MCI), newly discovered dementia, and prevalent dementia. METHODS: Subjects were a subset of the Mayo Clinic Study of Aging stratified-random sampling of Olmsted County, MN, residents aged 70 to 89 years. A neurologist reviewed provider-linked medical records to identify prevalent dementia (review date = index). Remaining subjects were invited to participate in prospective clinical/neuropsychological assessments; participants were categorized as CN, MCI, or newly discovered dementia (assessment date = index). Costs for medical services/procedures 1-year pre-index (excluding indirect and long-term care costs) were estimated using line-item provider-linked administrative data. We estimated contributions of care-delivery site and comorbid conditions (including and excluding neuropsychiatric diagnoses) to between-category cost differences. RESULTS: Annual mean medical costs for CN, MCI, newly discovered dementia, and prevalent dementia were $6042, $6784, $9431, $11,678, respectively. Hospital inpatient costs contributed 70% of total costs for prevalent dementia and accounted for differences between CN and both prevalent and newly discovered dementia. Ambulatory costs accounted for differences between CN and MCI. Age-, sex-, education-adjusted differences reached significance for CN versus newly discovered and prevalent dementia and for MCI versus prevalent dementia. After considering all comorbid diagnoses, between-category differences were reduced (e.g., prevalent dementia minus MCI (from $4842 to $3575); newly discovered dementia minus CN (from $3578 to $711)). Following the exclusion of neuropsychiatric diagnoses from comorbidity adjustment, between-category differences tended to revert to greater differences. CONCLUSIONS: Cost estimates did not differ significantly between CN and MCI. Substantial differences between MCI and prevalent dementia reflected high inpatient costs for dementia and appear partly related to co-occurring mental disorders. Such comparisons can help inform models aimed at identifying where, when, and for which individuals proposed interventions might be cost-effective.

Levodopa-carbidopa intestinal gel in advanced Parkinson's disease open-label study: interim results.

Levodopa-carbidopa intestinal gel (LCIG) delivered continuously via percutaneous endoscopic gastrojejunostomy (PEG-J) tube has been reported, mainly in small open-label studies, to significantly alleviate motor complications in Parkinson's disease (PD). A prospective open-label, 54-week, international study of LCIG is ongoing in advanced PD patients experiencing motor fluctuations despite optimized pharmacologic therapy. Pre-planned interim analyses were conducted on all enrolled patients (n = 192) who had their PEG-J tube inserted at least 12 weeks before data cutoff (July 30, 2010). Outcomes include the 24-h patient diary of motor fluctuations, Unified Parkinson's Disease Rating Scale (UPDRS), Clinical Global Impression-Improvement (CGI-I), Parkinson's Disease Questionnaire (PDQ-39), and safety evaluations. Patients (average PD duration 12.4 yrs) were taking at least one PD medication at baseline. The mean (±SD) exposure to LCIG was 256.7 (±126.0) days. Baseline mean "Off" time was 6.7 h/day. "Off" time was reduced by a mean of 3.9 (±3.2) h/day and "On" time without troublesome dyskinesia was increased by 4.6 (±3.5) h/day at Week 12 compared to baseline. For the 168 patients (87.5%) reporting any adverse event (AE), the most common were abdominal pain (30.7%), complication of device insertion (21.4%), and procedural pain (17.7%). Serious AEs occurred in 60 (31.3%) patients. Twenty-four (12.5%) patients discontinued, including 14 (7.3%) due to AEs. Four (2.1%) patients died (none deemed related to LCIG). Interim results from this advanced PD cohort demonstrate that LCIG produced meaningful clinical improvements. LCIG was generally well-tolerated; however, device and procedural complications, while generally of mild severity, were common.

Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study.

OBJECTIVE: The aim of this study was to estimate the efficacy of elagolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of endometriosis-associated pelvic pain. METHODS: This was a phase II, randomized, placebo-controlled parallel group study conducted at 37 US centers, consisting of an 8-week double-blind period followed by a 16-week open-label period. Patients were 137 women aged 18 to 49, with laparoscopically confirmed endometriosis and moderate to severe nonmenstrual pelvic pain and dysmenorrhea, who were administered elagolix 150 mg daily or placebo. The primary outcomes of the study were the daily assessment of dysmenorrhea, nonmenstrual pelvic pain and dyspareunia using a modified Biberoglu-Behrman scale. RESULTS: During the double-blind period, there were significantly greater mean reductions from baseline to week 8 in dysmenorrhea (-1.13 ± 0.11 vs. -0.37 ± 0.11, p<0.0001), nonmenstrual pelvic pain (-0.47 ± 0.07 vs. -0.19 ± 0.07, p = 0.0066), and dyspareunia scores (-0.61 ± 0.10 vs. -0.23 ± 0.10, p = 0.0070) in the elagolix group compared with placebo. Continued improvements were observed during the open-label treatment regardless of initial treatment allocation. Elagolix treatment was also associated with significant improvements in quality-of-life measures during the double-blind and open-label periods. The most common adverse events occurring with elagolix were nausea, headache and hot flush, each in 9.9% of patients. CONCLUSION: Elagolix effectively reduced endometriosis-associated pelvic pain over a 24-week period and was well-tolerated.

Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management.

BACKGROUND: Crohn's disease is a serious and debilitating gastrointestinal disorder with a high, unmet need for new treatments. Biologic agents have the potential to alter the natural course of Crohn's disease but present known risks of potential serious adverse events (SAEs). Previous studies have shown that patients are willing to accept elevated SAE risks in exchange for clinical efficacy. Gastroenterologists and patients may have similar goals of maximizing treatment benefit while minimizing risk; however, gastroenterologists may assess the relative importance of risk differently than patients. OBJECTIVE: To (a) understand how gastroenterologists caring for patients with Crohn's disease balance benefits and risks in their treatment decisions and (b) compare their treatment preferences with those of adult patients with Crohn's disease. METHODS: Both patient and gastroenterologist treatment preferences were elicited using a web-based, choice-format conjoint survey instrument. The conjoint questions required subjects to choose between 2 hypothetical treatment options with differing levels of treatment attributes. Patients evaluated the treatment options for themselves, and gastroenterologists evaluated the treatment options for each of 3 hypothetical patient types: (a) female aged 25 years with no history of Crohn's disease surgery (young), (b) male aged 45 years with 1 Crohn's disease surgery (middleaged), and (c) female older than 70 years with 4 Crohn's disease surgeries (older). Treatment attributes represented the expected outcomes of treatment: severity of daily symptoms, frequency of flare-ups, serious disease complications, oral steroid use, and the risks of 3 potentially fatal SAEs - lymphoma, serious or opportunistic infections, and progressive multifocal leukoencephalopathy (PML) - during 10 years of treatment. Maximum acceptable risk (MAR), defined as the highest level of SAE risk that subjects would accept in return for a given improvement in efficacy (i.e., the increase in treatment risk that exactly offsets the hypothetical increase in treatment benefit), was calculated using preference weights (parameter marginal log odds ratios) that were estimated with conjoint analysis (random parameters logit models). Gastroenterologists' and patients' mean MARs for 3 SAE risks were calculated for 6 improvements in Crohn's disease symptoms, and gastroenterologists' preference weights for each of the 3 patient profiles were compared. Gastroenterologists' MARs for a hypothetical middle-aged patient were then compared with predicted MARs derived using data from the patient study for male patients aged 40 to 50 years with 1 surgery. RESULTS: After exclusion of nonrespondents (n = 4,021 of 4,422 gastroenterologists; n = 681 of 1,285 patients) and nonevaluable respondents (n = 86 gastroenterologists; n = 24 patients), 315 gastroenterologists and 580 patients were included in the final analytic samples. There were no statistically significant differences in gastroenterologists' preference weights for the middle-aged versus young patient profiles. However, preference weights indicated that gastroenterologists are more concerned about 5% side-effect risks for the older patient profile than for the middle-aged patient profile. For symptomatic improvements from severe symptoms to remission, gastroenterologists' highest MARs were for lymphoma: 6.21%, 8.99%, and 25.00% for the young, middle-aged, and older patient types, respectively. In analyses of improvements from severe to moderate symptoms and from moderate symptoms to remission for hypothetical middle-aged patients, gastroenterologists' 10-year risk tolerance ranged between 1.96% lymphoma risk in return for an improvement from moderate symptoms to remission and 4.93% lymphoma risk for an improvement from severe to moderate symptoms; patients' 10-year risk tolerance for middle-aged patients ranged between 1.52% PML risk in return for an improvement from severe to moderate symptoms and 5.86% infection risk for an improvement from moderate symptoms to remission. On average, gastroenterologists and patients disagreed about how much risk is tolerable for improvements in efficacy. In exchange for improvements from severe to moderate symptoms for the middle-aged patient profile, gastroenterologists were significantly more tolerant than patients of treatment risks of PML (P < 0.001) and serious infection (P = 0.001) but not lymphoma (P = 0.230). In contrast, in exchange for improvements from moderate symptoms to remission for the same patient profile, patients were significantly more tolerant than gastroenterologists of treatment risks for serious infection (P < 0.001) and lymphoma (P < 0.001) but not PML (P = 0.158). CONCLUSIONS: Gastroenterologists and patients have well-defined preferences among treatment attributes and are willing to accept tradeoffs between efficacy and treatment risks. However, risk tolerance varies depending on the type of patient for whom gastroenterologists are being asked to consider treatment. In rating treatment preferences for patients with a middle-aged profile, gastroenterologists are less tolerant of SAE risks than patients in exchange for improvement from moderate symptoms to remission.

Are adult patients more tolerant of treatment risks than parents of juvenile patients?

Understanding patient-specific differences in risk tolerance for new treatments that offer improved efficacy can assist in making difficult regulatory and clinical decisions for new treatments that offer both the potential for greater effectiveness in relieving disease symptoms, but also risks of disabling or fatal side effects. The aim of this study is to elicit benefit-risk trade-off preferences for hypothetical treatments with varying efficacy and risk levels using a stated-choice (SC) survey. We derive estimates of "maximum acceptable risk" (MAR) that can help decisionmakers identify welfare-enhancing alternatives. In the case of children, parent caregivers are responsible for treatment decisions and their risk tolerance may be quite different than adult patients' own tolerance for treatment-related risks. We estimated and compared the willingness of Crohn's disease (CD) patients and parents of juvenile CD patients to accept serious adverse event (SAE) risks in exchange for symptom relief. The analyzed data were from 345 patients over the age of 18 and 150 parents of children under the age of 18. The estimation results provide strong evidence that adult patients and parents of juvenile patients are willing to accept tradeoffs between treatment efficacy and risks of SAEs. Parents of juvenile CD patients are about as risk tolerant for their children as adult CD patients are for themselves for improved treatment efficacy. SC surveys provide a systematic method for eliciting preferences for benefit-risk tradeoffs. Understanding patients' own risk perceptions and their willingness to accept risks in return for treatment benefits can help inform risk management decision making.

Health-related quality of life during natalizumab maintenance therapy for Crohn's disease.

OBJECTIVES: We evaluated the effects of treatment on health-related quality of life (HRQoL) during a randomized controlled trial of natalizumab maintenance therapy (ENACT-2) using both disease-specific and generic measures. METHODS: Crohn's disease patients who received natalizumab as induction therapy in ENACT-1 (N=724) and responded (N=339) were re-randomized to ENACT-2 in which they received natalizumab 300 mg (N=168) or placebo (N=171) every 4 wk for 48 additional wk. Outcome measures were the change from baseline on the inflammatory bowel disease questionnaire (IBDQ), the short form-36 (SF-36), the EuroQol-5D (EQ-5D), and a subject global assessment. RESULTS: At entry into ENACT-1, scores indicated substantially impaired HRQoL for both the disease-specific and general measures. Natalizumab responders showed clinically meaningful improvement in HRQoL over the course of the ENACT-1 study. During maintenance therapy, IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-randomized to receive the drug in ENACT-2 (N=168) remained stable, while those re-randomized to placebo (N=171) worsened. At week 60, 48 wk after the initiation of maintenance therapy, the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab (P<0.001 for all scales). The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36. CONCLUSIONS: The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy.

Crohn's disease patients' risk-benefit preferences: serious adverse event risks versus treatment efficacy.

BACKGROUND & AIMS: Regulatory assessments of drug risks do not routinely consider patient preferences, despite evidence that some patients are willing to accept increased side-effect risk in exchange for therapeutic benefits. The aim of this study is to estimate the willingness of Crohn's disease (CD) patients to accept life-threatening adverse event risks in exchange for CD symptom relief. METHODS: Patients with CD completed choice-format conjoint trade-off tasks involving hypothetical treatments with varying efficacy and risk levels. The treatment features included daily symptoms and activity limitations, serious complications (fistulas, abscesses, bowel obstructions), time between flare-ups, oral steroid use and risk of 3 serious adverse events (SAEs) known to be associated with CD treatment (progressive multifocal leukoencephalopathy (PML), serious infections, and lymphoma). The mean maximum acceptable annual risk (MAR) for each of the SAEs was calculated for various levels of clinical benefit. RESULTS: Daily symptom severity was the most important factor in treatment preferences. Higher MAR was observed for trade-off tasks involving higher levels of clinical benefit. The MAR was similar across the 3 SAEs. For improvements from severe daily symptoms to remission and from moderate daily symptoms to remission, the MARs ranged from 0.69% to 0.81% and from 0.39% to 0.55%, respectively. CONCLUSIONS: Patients with CD have well-defined preferences among treatment attributes and are willing to accept tradeoffs among attributes. The patients indicated they are willing to accept elevated SAE risks in exchange for clinical efficacy. The perspective of the patients on the benefit versus risk balance can assist in making treatment and regulatory decisions.

The association of consumer expectations, experiences and satisfaction with newly prescribed medications.

OBJECTIVE: To examine the association between medication expectations and subsequent experience on treatment satisfaction and intention to continue using the medication. METHODS: A longitudinal study with two surveys administered to each patient. Patients prescribed a new medication were recruited in pharmacies within Michigan. Medication-related expectations were evaluated at baseline. Experiences, satisfaction and intent to continue were evaluated a month later. Analyses used included factorial ANOVA models, multiple linear regressions and structural equation modeling (SEM). Impact of satisfaction on intention to continue was evaluated using correlation analysis and SEM. RESULTS: A total of 344 usable responses were obtained. SEM showed that expectation scores were not associated with both experience (path coefficient = 0.10) and satisfaction (path coefficient = 0.02, NS). On the other hand, experience was strongly associated with satisfaction (path coefficient = 0.89) and satisfaction was strongly associated with intent to continue using the new medication (path coefficient = 0.81). CONCLUSIONS: This study empirically supports the value of the patient's experience and its contribution to satisfaction, which in turn is associated with intended continued use mainly due to greater effectiveness of the newly prescribed medication. Satisfied consumers should be more adherent, thus enhancing the probability of positive therapeutic outcomes.