Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior (forgetfulness or carelessness). Our objectives were to: (1) study the prevalence and ...predictors of unintentional non-adherence; and (2) explore the interrelationship between intentional and unintentional non-adherence in relation to patients' medication beliefs.
We conducted a cross-sectional survey of adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, or depression from the Harris Interactive Chronic Illness Panel. The analytic sample for this study included 24,017 adults who self-identified themselves as persistent to prescription medications for their index disease. They answered three questions on unintentional non-adherence (forgot, ran out, being careless), 11 questions on intentional non-adherence, and three multi-item scales assessing perceived need for medication (k = 10), perceived medication concerns (k = 6), and perceived medication affordability (k = 4). Logistic regression was used to model predictors of each unintentional non-adherence behavior. Baron and Kenny's regression approach was used to test the mediational effect of unintentional non-adherence on the relationship between medication beliefs and intentional non-adherence. Bootstrapping was employed to confirm the statistical significance of these results.
For the index disease, 62% forgot to take a medication, 37% had run out of the medication, and 23% were careless about taking the medication. Common multivariate predictors (p < .001) of the three behaviors were: (1) lower perceived need for medications; (2) more medication affordability problems; (3) worse self-rated health; (4) diabetes or osteoporosis (relative to hypertension); and (5) younger age. Unique statistically-significant predictors of the three behaviors were: (a) 'forgot to take medications' - greater concerns about the index medication and male gender; (b) 'run out of medications' - non-white race, asthma, and higher number of total prescription medications; (c) 'being careless' - greater medication concerns. Mediational tests confirmed the hypothesis that the effect of medication beliefs (perceived need, concerns, and affordability) on intentional non-adherence is mediated through unintentional non-adherence.
For our study sample, unintentional non-adherence does not appear to be random and is predicted by medication beliefs, chronic disease, and sociodemographics. The data suggests that the importance of unintentional non-adherence may lie in its potential prognostic significance for future intentional non-adherence. Health care providers may consider routinely inquiring about unintentional non-adherence in order to proactively address patients' suboptimal medication beliefs before they choose to discontinue therapy all together.
Background Given its public health impact, there is need for broad and representative data on the humanistic burden of atopic dermatitis (AD). Objective To establish the humanistic burden of AD in US ...adults. Methods Data were from the 2013 US National Health and Wellness Survey; AD self-reports were propensity-matched with non-AD controls and with psoriasis controls. Bivariate analyses were conducted on burden outcomes between the AD and control groups. Results Demographics and baseline characteristics were comparable between matched groups. Subjects with AD (n = 349) versus non-AD controls (n = 698) had significantly higher rates of anxiety, depression, and sleep disorders (29.8%, 31.2%, and 33.2% vs 16.1%, 17.3%, and 19.2%, respectively all P < .001); a lower Short Form-36 v2 mental component summary score (44.5 vs 48.0, respectively P < .001); a lower physical component summary score (47.6 vs 49.5, respectively P = .004), and lower health utilities (0.67 vs 0.72, respectively P < .001) in addition to a higher work absenteeism rate (9.9% vs 3.6%, respectively P < .001) and activity impairment rate (33.6% vs 25.2%, respectively P < .001). Subjects with AD and psoriasis controls (n = 260 each) showed similar impairment in health-related quality of life and productivity. Limitations Data were self-reported. Conclusion AD is associated with a substantial humanistic burden that is similar in magnitude to that of psoriasis, which is also recognized for its debilitating symptoms, indicating the need for more effective treatments for AD.
Summary Background Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic ...diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. Methods In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov , NCT02260986. Findings Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% 125 patients who received dupilumab plus topical corticosteroids qw and 39% 41 patients who received dupilumab q2w plus topical corticosteroids vs 12% 39 patients who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% 204 and 69% 73 vs 23% 73; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids. Interpretation Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety. Funding Sanofi and Regeneron Pharmaceuticals Inc.
•In this pooled analysis dupilumab significantly improved signs and symptoms of AD.•Dupilumab treatment alleviated pain/discomfort on the EuroQoL-5D.•Patient distribution within responder categories ...improved over time with dupilumab.•No new safety signals were observed with dupilumab.•Dupilumab had an overall favorable benefit-risk profile.
Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD).
To report a pooled analysis of these trials to further explore dupilumab’s effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety.
A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo.
Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator’s Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–<90%/≥50–<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1–3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo.
Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
There is a lack of data on the burden of atopic dermatitis (AD) in adults relative to the general population.
To characterize the AD burden in adult patients relative to both matched non-AD controls ...and matched patients with psoriasis in terms of comorbidities, health care resource utilization (HCRU), and costs.
Adults (≥18 years) who self-reported a diagnosis of AD or psoriasis and adult non-AD controls were identified from the 2013 US National Health and Wellness Survey. Patients with AD were propensity score–matched with non-AD controls and patients with psoriasis on demographic variables. Patient-reported outcomes were analyzed between matched cohorts.
Patients with AD had a significantly greater risk for atopic comorbidities, as well as significantly greater HCRU and total cost compared with non-AD controls. The burden of AD was generally comparable to that of psoriasis, although patients with AD reported increased use of emergency room visits compared with patients with psoriasis.
Patient-reported data are susceptible to recall bias and erroneous classification.
Adult patients with AD reported a substantial disease burden, suggesting an unmet need for more effective AD treatment options.
Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general ...population. Japanese adults (≥18 years) with a self‐reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity‐score matched with non‐atopic dermatitis controls (1:2 ratio) on demographic variables. Patient‐reported outcome data on comorbidities, mood and sleep disorders, health‐related quality of life, work productivity and activity impairment, and health‐care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as “moderate/severe” and 348 (54.5%) as “mild”. The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health‐related quality of life, higher overall work and activity impairment, and higher health‐care resource utilization (all P < 0.001). Self‐rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.
Background Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies. Objective We sought to evaluate dupilumab treatment on patient-reported ...outcomes in adults with moderate to severe AD. Methods Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol. Results Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale ( P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol ( P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms ( P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns. Limitations There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points. Conclusion Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits.
Objectives: The Atopic Dermatitis Control Tool (ADCT) was designed to evaluate patient-perceived AD control and facilitate patient-physician discussion on long-term disease control.
Methods: The ...study was performed in adult patients with AD. Development of the ADCT followed US Food and Drug Administration (FDA) guidelines on patient-reported outcome measures (PROMs). Qualitative research, including targeted literature review, interviews with clinical experts, and combined concept elicitation/cognitive debriefing with patients with AD, was conducted to provide a list of comprehensive concepts capturing AD control per physician and patient perspectives. Quantitative methods assessed psychometric properties of the instrument and defined the threshold for AD control.
Results: The resulting pilot six-item ADCT, reflecting key concepts related to AD control, had 7-day recall and assessed symptoms and impacts on patients' everyday lives by severity and/or frequency. The ADCT showed good content validity (well understood by adult patients with AD), and quick completion time (<2 min). Psychometric analysis indicated no floor/ceiling effects for response distributions, particularly strong (r ≥ 0.80) inter-item correlations for the six ADCT items, robust construct validity (r > 0.50), and item-level discriminating ability (p < .03); this supported the derivation of a total score based on responses to all items. ADCT total score showed evidence of strong internal consistency reliability (Cronbach's alpha >0.80). A score ≥7 points was identified as an optimum threshold to identify patients whose AD is "not in control."
Conclusions: No single validated instrument has been available to holistically evaluate patient-perceived AD control. The newly developed ADCT displays good-to-excellent content validity, construct validity, internal consistency, reliability, and discriminating ability.
To evaluate the impact of atopic dermatitis on families of pediatric patients.
This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with atopic dermatitis and ...their parents and caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children and adolescents with atopic dermatitis and their parents and caregivers were identified by the International Study of Asthma and Allergies in Childhood criteria and ever being told by a physician that they had “eczema”. Atopic dermatitis severity was assessed using the Patient-Oriented Eczema Measure and the Patient Global Assessment. Atopic dermatitis impact on families’ lives was evaluated using the Dermatitis Family Impact questionnaire and stand-alone questions on hours of atopic dermatitis-related care (past week) and missed work days (past 4 weeks) owing to their child’s atopic dermatitis.
A total of 7465 pairs of pediatric participants with atopic dermatitis and their parents or caregivers were surveyed. Across age groups, the Dermatitis Family Impact questionnaire total score for all regions ranged from 7.1 to 8.6, 13.2 to 14.9, and 17.0 to 17.2 for Patient-Oriented Eczema Measure mild, moderate, and severe atopic dermatitis, respectively. Subscale scores showed that greater atopic dermatitis severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with atopic dermatitis severity.
Across pediatric age groups and geographic regions, greater atopic dermatitis severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life.
Abstract
Background:
The literature on nonfulfillment of prescription medications spans over three decades of work. There is a wide variation in reported nonfulfillment rates, but no previous study ...has systematically reviewed this literature to explore the reasons behind this variation.
Objective:
The objective of this study was to review estimates of medication nonfulfillment rates and published reasons for nonfulfillment and explore whether nonfulfillment rates vary by study variables.
Methods:
Articles were identified through searches conducted on MEDLINE, CINAHL, Psych Info, and EMBASE, and review of relevant reference citations. Methodological variables, nonfulfillment rate, and unit of analysis (i.e., patient or prescription) were abstracted from each article selected for review. Mean and median nonfulfillment rates for groups categorized by unit of analysis and selected methodological variables (method for assessing nonfulfillment, sample characteristics, disease subgroup, sample size, country of data collection, recall period or time allowed before classifying as nonfulfillment, and year of study) were calculated. Reasons for nonfulfillment were abstracted from all articles that included a relevant discussion.
Findings:
A total of 79 studies reporting pure nonfulfillment rates (59 at the patient level and 20 at the prescription level) and six studies reporting nonfulfillment rates in combination with nonpersistence rates were included. There was a wide variation in nonfulfillment rates reported by the studies - from 0.5% to 57.1%. The three primary reasons for nonfulfillment identified from this review were perceived concerns about medications, lack of perceived need for medications, and medication affordability issues.
Conclusion:
To the best of the authors’ knowledge, this study is the first narrative systematic review on nonfulfillment of prescription medications. Despite the wide variation in individual study rates, the mean and median rates across different modes of data collection and sources of data were in a relatively narrow range (11% to 19%) and surprisingly close to the overall mean (16.4%) and median (15%.0) rates for all studies. The reasons for nonfulfillment identified through this review address barriers to nonfulfillment at the patient, physician, and health system level and thus bear important implications for policy makers.
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