The Family Impact of Atopic Dermatitis in the Pediatric Population: Results from an International Cross-sectional Study.

OBJECTIVE: To evaluate the impact of atopic dermatitis on families of pediatric patients. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health-related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient-reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. METHODS: Following a 4-week mometasone furoate nasal spray run-in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires. RESULTS: Following 16 weeks of treatment, the proportion of patients with moderate-to-severe CRSwNP (VAS > 3-10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT-22, SF-36, and EQ-5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P = .015) and significantly greater improvement (vs placebo) in the SNOT-22 item "reduced productivity." CONCLUSIONS: In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity.

Dupilumab improves symptoms, quality of life, and productivity in uncontrolled persistent asthma.

BACKGROUND: In a pivotal, phase 2b study (NCT01854047) in patients with uncontrolled persistent asthma, despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2 agonists, dupilumab improved lung function, reduced severe exacerbations, and showed an acceptable safety profile. OBJECTIVE: To assess the impact of dupilumab on asthma control, symptoms, quality of life (QoL), and productivity. METHODS: Data are shown for the intention-to-treat population receiving dupilumab 200/300 mg every 2 weeks (doses being assessed in phase 3; NCT02414854), or placebo. Predefined analyses of total scores were conducted at week 24 for the 5-item Asthma Control Questionnaire (ACQ-5), patient-reported morning/evening (AM/PM) asthma symptoms, Asthma Quality of Life Questionnaire (AQLQ), and asthma-related productivity loss. Responder rate analyses for these measures, subgroup analyses by baseline characteristics, and asthma-related productivity loss analyses were conducted post hoc. RESULTS: Data from 465 patients were analyzed (158 placebo; 307 dupilumab). Both dupilumab doses significantly improved scores through week 24 (all outcomes, overall population). The proportion of patients meeting or exceeding the minimal clinically important difference for the overall population were significantly greater vs placebo (P < .05) for ACQ-5 (range, 72.6%-76.7% vs 61.4%), for AM/PM asthma symptoms score (48.7%-54.1% vs 34.2% and 52.7%-53.5% vs 34.2%, respectively) and for AQLQ (64.0%-65.0% vs 51.3%). The effect of dupilumab was consistent across most subgroups. Productivity loss was significantly higher in placebo- vs dupilumab-treated patients (P < .0001). CONCLUSION: Dupilumab produced significant, clinically meaningful improvements in asthma control, symptoms, QoL, and productivity. REGISTRATION: ClinicalTrials.gov Identifier: NCT01854047.

Burden of illness in adults with atopic dermatitis: Analysis of National Health and Wellness Survey data from France, Germany, Italy, Spain, and the United Kingdom.

BACKGROUND: The disease burden of atopic dermatitis (AD) in European populations is not well known. OBJECTIVE: To establish the disease burden in European adult patients with AD. METHODS: Data were from the 2016 National Health and Wellness Survey conducted in France, Germany, Italy, Spain, and the United Kingdom. Bivariate analyses were conducted on outcomes between controls without AD matched to patients with self-reported AD (both n = 1860). RESULTS: Patients with AD and a subset of patients with inadequately controlled AD (IC-AD) versus controls without AD, respectively, reported significantly higher (P < .001) 36-Item Short Form Health Survey Physical and Mental Component Summaries (PCS, MCS), and anxiety (31.9% and 51.7% vs 14.4%), depression (25.8% and 36.2% vs 12.9%), and sleep disorder (22.7% and 39.7% vs 12.6%) prevalences. Patients with IC-AD versus controls without AD reported significantly greater (P < .001) overall work (57.1% vs 23.7%) and activity impairment (51.7% vs 26.5%). In addition, 21.6% of patients with AD and 37.9% of patients with IC-AD reported ≥1 emergency department visit in the previous 6 months versus 16.5% of controls without AD, and 93.1% of patients with AD versus 84.2% of those without AD had ≥1 clinician visit (both P < .001). Of these, patients with IC-AD showed greater burden on most outcomes than patients with controlled AD. LIMITATIONS: Low response rate, possible selection bias due to survey technology availability, and patient-reported data susceptible to recall bias. CONCLUSION: Patients with AD reported significant burden on health, health-related quality of life, productivity, activities, and health care.

Validation of the Atopic Dermatitis Control Tool (ADCT©) using a longitudinal survey of biologic-treated patients with atopic dermatitis.

BACKGROUND: The Atopic Dermatitis Control Tool (ADCT©) is a brief patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control; six AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions. This study assessed the reliability, validity, and responsiveness of the ADCT in a longitudinal context, and provided thresholds to identify meaningful within-person change. METHODS: Data were from a prospective, longitudinal patient survey study of real-world effectiveness of dupilumab in patients with AD. Eligible patients completed a baseline survey before starting dupilumab and were followed at Months 1, 2, 3, and 6 post-initiation as they became eligible. RESULTS: Psychometric analyses confirmed internal consistency; Cronbach's α coefficients were consistently above the threshold of 0.70 across each follow-up; item-to-total correlations were above the threshold of r ≥ 0.50. High correlations between the ADCT and the Dermatology Life Quality Index (DLQI) and skin pain supported construct validity, while known-group validity was shown on Patient Global Assessment of Disease (PGAD) overall well-being subgroups with worse AD-related overall well-being having higher mean ADCT total scores at all time points. The ability of the ADCT to detect change was confirmed; the threshold for meaningful within-person change was estimated to be 5 points. Finally, test-retest reliability was confirmed in subgroups of patients with stable PGAD responses. CONCLUSIONS: Our findings confirm that the ADCT is a valid and reliable tool for assessing AD control.

The burden of atopic dermatitis in US adults: Health care resource utilization data from the 2013 National Health and Wellness Survey.

BACKGROUND: There is a lack of data on the burden of atopic dermatitis (AD) in adults relative to the general population. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Patient-reported data are susceptible to recall bias and erroneous classification. CONCLUSIONS: Adult patients with AD reported a substantial disease burden, suggesting an unmet need for more effective AD treatment options.

Impact of atopic dermatitis on health-related quality of life and productivity in adults in the United States: An analysis using the National Health and Wellness Survey.

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.

Prevalence and morphological analysis of isthmuses in mandibular molars of the Indian population: A micro-computed tomographic study.

Objectives: This study evaluated the prevalence, configurations, and correlation of isthmuses at coronal, middle, and apical root 3rd in mandibular molars of the Indian population using micro-computed tomography µCT). Materials and Methods: One hundred and five permanent mandibular molar teeth were scanned under µCT. The axial sections were analyzed at the coronal, middle, and apical thirds of the root for isthmus types and classified according to Hsu and Kim's classification. Descriptive statistics for each isthmus type were calculated. The correlations between the apical, middle, and coronal thirds of the root were determined using Pearson's correlation coefficient. Results: Type IV isthmus was the most common in the coronal third of the mesial root of mandibular 1st molar (42.9%), while Type V was prevalent in the coronal third of the mesial root of 2nd molar (42.9%). Type I isthmus was found to be highly prevalent in the middle 3rd (71.4%) and apical 3rd (61.9%) of mesial roots of 1st molars, and in the middle 3rd (71.4%) and apical 3rd (42.9%) of mesial roots of 2nd molars. Type V isthmus was the most prevalent in all the thirds of the distal roots of both 1st and 2nd molars, ranging from 40% to 50%. Furthermore, a strong correlation of 0.965 (P < 0.01) was found between the isthmuses in the apical and middle thirds of roots. Conclusion: There are variations in the prevalence and type of isthmuses across different sections of the root, including the presence of atypical isthmuses. Micro-CT with high-resolution imaging and three-dimensional reconstruction is crucial for investigating root canal morphology. Clinicians could benefit from considering demographic characteristics to better predict the presence of isthmus variations. Clinical Relevance: The isthmus configurations and frequency differ at each section of mandibular teeth.

Influence of hyperpolarization caused by high salt diet on ß-adrenoceptor-mediated responses in rat pulmonary artery.

The effect of high salt diet on ß-adrenoceptor-mediated response was assessed in rat-isolated pulmonary arteries. Isoprenaline-induced relaxations were not different in tissues from rats on either, high salt or regular diets. However, acidic buffer (pH 6.4) alone and in combination with Ba2+ or Nω-nitro-L-arginine methyl ester (L-NAME) significantly attenuated isoprenaline-induced relaxations in tissues from rats on high salt compared with those on a regular diet. Also, Ba2+ and ouabain together produced a significantly greater inhibition of isoprenaline-induced relaxation in tissues from rats on high salt when compared with those on the regular diet. The resting membrane potential of smooth muscle cells of pulmonary arteries of rats on high salt diet compared with regular diet was more negative (ie, hyperpolarized) than that on the regular diet. This hyperpolarization was reversed on exposure of blood vessels to acidic buffer and/or Ba2+ and ouabain combined but not L-NAME. Treatment with isoprenaline did not cause further hyperpolarization of smooth muscle cells of arteries from rats on the high salt diet. Taken together, the electrical changes due to the high salt diet can be attributed to the opening of K+ channels (2 pore acid-sensitive K+ channels and K(ir2.1)) and the activation of Na+/K+-ATPase. Furthermore, hyperpolarization observed after consumption of high salt diet seems to preserve ß-adrenoceptor-mediated vasorelaxation.

Lifelong Impact of Severe Atopic Dermatitis on Quality of Life: A Case Report.

Severe, uncontrolled atopic dermatitis (AD) persisting from childhood to adulthood can have enduring quality of life (QoL) impacts on daily functioning, academics, career, family and social life, and mental health. In addition, AD has an impact on direct and indirect healthcare resource utilization. Several studies have attempted to quantify the quality of life and direct/indirect economic burden of AD. However, these estimates may not capture the more intangible disease-related burden and associated economic burden. This was a qualitative case report that aimed to investigate the full lifetime impact of severe, uncontrolled AD on all aspects of a single patient's life. This case report emphasizes the enormous cumulative lifetime impact of severe, uncontrolled AD and where the qualitative indirect impact may not be fully captured. After obtaining consent, a patient, diagnosed with severe AD since birth, was asked close- and open-ended questions about AD history, direct and indirect healthcare resource utilization, and impact of AD on work, home, family, social life, daily functioning, and mental health over the course of her lifetime. Our patient attributed her severe, uncontrolled AD since birth to causing poor sleep quality, depression, anxiety, and difficulty with social connections and to her choosing an alternative, less physically demanding career. Early effects on sleep and school performance, along with impact on social connections, likely contribute to weaker career opportunities and further social isolation with age.

Comparative Evaluation of Dentinal Microcrack Formation before and after Root Canal Preparation Using Rotary, Reciprocating, and Adaptive Instruments at Different Working Lengths-A Micro-computed Tomographic Study.

INTRODUCTION: This study aimed to compare root dentinal microcrack formation after root canal shaping using rotary, reciprocating, and adaptive instruments at different working lengths using micro-computed tomographic imaging. METHODS: One hundred eighty extracted mature mandibular molar mesial roots with 2 separate canals were selected. The mesial roots were resected at the cementoenamel junction and randomly divided into 4 groups (n = 45) based on the nickel-titanium file system used: ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Gold (Dentsply Maillefer), Twisted File Adaptive (SybronEndo, Orange, CA), and Reciproc Blue (VDW, Munich, Germany). Each of the 4 groups were then subdivided into 3 groups (n = 15) depending on the working length used for root canal preparation (ie, instrumentation 1 mm short, flush, and 1 mm beyond the major apical foramen). The roots were imaged with micro-computed tomographic scanning before and after root canal preparation. The cross-sectional images generated were screened to detect the presence of new microcracks. RESULTS: The ProTaper Universal system significantly increased the number of postinstrumentation microcracks at all working lengths (P ≤ .05). No significant increase (P > .05) in postinstrumentation microcracks was observed in the ProTaper Gold, Twisted File Adaptive, or Reciproc Blue groups. CONCLUSIONS: Rotary instrumentation induced a higher number of dentinal microcracks compared with reciprocating and adaptive instruments. Instrumentation at different working lengths did not significantly influence the formation of dentinal microcracks.

The Use of Real-World Data to Evaluate the Association Between Atopic Dermatitis and Cardiovascular Disease: A Retrospective Claims Analysis.

INTRODUCTION: Atopic dermatitis (AD) is a systemic inflammatory condition that may increase the risk of cardiovascular disease (CVD); however, ongoing debate exists surrounding its direct association. We aimed to elucidate whether AD contributes to a higher incidence of CVD and major adverse cardiovascular events (MACE) in adult patients with AD, independent of metabolic disorders. METHODS: We retrospectively analyzed a large US-based population of patients with AD (≥ 18 years of age). Logistic regression estimated the risk of CVD and MACE in adult patients with AD, independent of metabolic disorders (including diabetes, hypertension, and obesity). RESULTS: The odds ratio (OR; 95% confidence interval [CI]) for patients without metabolic disorders was 1.25 (1.13, 1.39) for CVD and 1.22 (1.01, 1.47) for MACE. The OR (95% CI) for AD patients with metabolic disorders was 1.09 (1.07, 1.12) for CVD and 1.14 (1.09, 1.18) for MACE. This trend was even more pronounced after long-term follow-up (≥ 3 years). Lifestyle and health behavioral factors of the subjects were not available in the dataset. The lack of control for these factors could potentially confound our results. CONCLUSIONS: Atopic dermatitis may contribute to the risk of developing CVD and MACE in adults, independent of metabolic disorders.

Data Mining of Free-Text Responses: An Innovative Approach to Analyzing Patient Perspectives on Treatment for Chronic Rhinosinusitis with Nasal Polyps in a Phase IIa Proof-of-Concept Study for Dupilumab.

PURPOSE: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. PATIENTS AND METHODS: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. RESULTS: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. CONCLUSION: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https://www.clinicaltrials.gov/ct2/show/NCT01920893.

Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease.

Vitamin D insufficiency is common in patients with chronic kidney disease (CKD) and may contribute to mineral bone disease. In a prospective interventional study, we estimated the prevalence of vitamin D insufficiency (serum 25-hydroxyvitamin D3 [25OHD] < 30 ng/ml), and examined the effect of high-dose (600,000 IU) cholecalciferol supplementation after 6 weeks on serum 25OHD and parathyroid hormone (PTH) levels in children with CKD stages 2-4. Forty-two children (86% boys) with a mean age of 7.7 ± 3.8 (range 2--5) years were studied. Thirty-seven children (82.1%) had vitamin D insufficiency; 18 (42.8%) had 25OHD < 16 ng/ml. The median 25OHD increased significantly from 16.7 (95% CI 11.3, 19.8) to 46.2 (34.5, 44.6) ng/ml in patients with vitamin D insufficiency (P <0.001). The median PTH decreased significantly from 51.3 (95% CI 46.7, 71.5) to 37.1 (29.0, 54.6) pg/ml (P = 0.003). Nineteen patients (47.5%) had >30% reduction in the PTH after supplementation. Serum calcium, phosphorus, and estimated GFR did not change significantly. We conclude that vitamin D insufficiency is highly prevalent in children with CKD stages 2-4. High-dose cholecalciferol is safe and effective in correcting vitamin D insufficiency and results in a significant reduction in PTH levels in vitamin D-insufficient children.

Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns Among Rheumatologists in Europe and Japan.

INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) are commonly used as first-line therapy (biologic disease-modifying antirheumatic drug [bDMARD] and targeted synthetic DMARD [tsDMARD]: defined as targeted therapy) for patients with moderate-to-severe rheumatoid arthritis (RA), usually combined with conventional synthetic DMARDs (csDMARDs) but sometimes as monotherapy. If treatment fails, patients cycle to another TNFi (cycling) or switch to a targeted therapy with a different mode of action (MOA; switching). The study aimed to examine prescribing patterns and reasons for current RA treatment practice in Europe (EU5: France, Germany, Italy, Spain, UK) and Japan. METHODS: Data were collected from the Adelphi Disease Specific Programme™ (DSP; Q1-Q2 2017). Rheumatologists seeing ≥ 10 (EU5) and ≥ 5 (Japan) patients with RA a month completed Patient Record Forms. Patients ≥ 18 years old, with RA diagnosis and complete RA-targeted therapy history were included. Patients were grouped based on first-line targeted therapy class, and on whether first-line targeted therapy was monotherapy (targeted therapy alone) or combination therapy (targeted therapy and csDMARD). Those patients receiving TNFi at first-line and with ≥ 1 targeted therapy were classified as TNFi cyclers or MOA switchers. Univariate analysis compared factors across groups. Patient demographics and characteristics compared across groups; physician reasoning for targeted therapy change; and time to discontinuation of targeted therapy. RESULTS: In EU5 and Japan, respectively, 1741 and 147 patients were included; at first-line, 80.8% and 64.6% received TNFi and 76.0% and 77.6% received combination therapy. Overall in EU5, more combination therapy than monotherapy patients reached maximum csDMARD dose before first-line targeted therapy (P < 0.05); disease severity was higher in patients initiating TNFi versus non-TNFi (P < 0.05). In Japan, trends were similar but not significant. The most common reason physicians gave for changing therapy following first-line targeted therapy was 'secondary lack of efficacy' (EU5: 46.2%; Japan: 53.8%). In EU5 and Japan, respectively, of 365 and 22 patients who received second-line targeted therapy, 52.1% and 54.5% were MOA switchers. In EU5, TNFi cyclers had longer time from diagnosis to second-line targeted therapy initiation than MOA switchers (P = 0.04). CONCLUSIONS: TNFis were the most commonly prescribed targeted therapy at first-line. Between 10 and 20% of patients prescribed a TNFi as first-line targeted therapy did so without concomitant csDMARD. Almost half of patients cycled to another TNFi at second-line.

Evaluating patient-perceived control of atopic dermatitis: design, validation, and scoring of the Atopic Dermatitis Control Tool (ADCT).

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.

Outcomes of tumor necrosis factor inhibitor cycling versus switching to a disease-modifying anti-rheumatic drug with a new mechanism of action among patients with rheumatoid arthritis.

OBJECTIVES: To examine treatment patterns, treatment effectiveness, and treatment costs for 1 year after patients with rheumatoid arthritis switched from a tumor necrosis factor inhibitor (TNFi) (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab), either cycling to another TNFi ("TNFi cyclers") or switching to a new mechanism of action (abatacept, tocilizumab, or tofacitinib) ("new MOA switchers"). METHODS: This retrospective cohort study used administrative claims data for a national insurer. Treatment persistence (without switching again, restarting, or discontinuing), treatment effectiveness (defined below), and costs were assessed for the 12-month post-switch period. Patients were "effectively treated" if they satisfied all six criteria for a treatment effectiveness algorithm (high adherence, no dose increase, no new conventional synthetic disease-modifying anti-rheumatic drug, no subsequent switch in therapy, no new/increased oral glucocorticoids, and <2 glucocorticoid injections). Multivariable logistic models were used to adjust for baseline factors. RESULTS: The database included 581 new MOA switchers and 935 TNFi cyclers. New MOA switchers were 39% more likely than TNFi cyclers to persist after the switch (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.12-1.74; p = .003) and 36% less likely to switch therapy again (OR = 0.64; 95% CI = 0.51-0.81; p < .001). New MOA switchers were 43% more likely than TNFi cyclers to be effectively treated (OR = 1.43; 95% CI = 1.11-1.85; p = .006). New MOA switchers had 16% lower drug costs than TNFi cyclers (cost ratio = 0.84; 95% CI = 0.79-0.88; p < .001) and 11% lower total costs of rheumatoid arthritis-related medical care (cost ratio = 0.89; 95% CI = 0.84-0.94; p < .001). LIMITATIONS: Claims payments may not reflect rebates or other cost offsets. Medical and pharmacy claims do not include clinical end-points or reasons that lead to new MOA switching vs TNFi cycling. CONCLUSIONS: These results support switching to a new MOA after a patient fails treatment with a TNFi, which is consistent with recent guidelines for the pharmacologic management of established rheumatoid arthritis.

Economic Evaluation of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults.

INTRODUCTION: Dupilumab significantly improves signs and symptoms of atopic dermatitis (AD), including pruritus, symptoms of anxiety and depression, and health-related quality of life versus placebo in adults with moderate-to-severe AD. Since the cost-effectiveness of dupilumab has not been evaluated, the objective of this analysis was to estimate a value-based price range in which dupilumab would be considered cost-effective compared with supportive care (SC) for treatment of moderate-to-severe AD in an adult population. METHODS: A health economic model was developed to evaluate from the US payer perspective the long-term costs and benefits of dupilumab treatment administered every other week (q2w). Dupilumab q2w was compared with SC; robustness of assumptions and results were tested using sensitivity and scenario analyses. Clinical data were derived from the dupilumab LIBERTY AD SOLO trials; healthcare use and cost data were from health insurance claims histories of adult patients with AD. The annual price of maintenance therapy with dupilumab to be considered cost-effective was estimated for decision thresholds of US$100,000 and $150,000 per quality-adjusted life-year (QALY) gained. RESULTS: In the base case, the annual maintenance price for dupilumab therapy to be considered cost-effective would be $28,770 at a $100,000 per QALY gained threshold, and $39,940 at a $150,000 threshold. Results were generally robust to parameter variations in one-way and probabilistic sensitivity analyses. CONCLUSION: Dupilumab q2w compared with SC is cost-effective for the treatment of moderate-to-severe AD in US adults at an annual price of maintenance therapy in the range of $29,000-$40,000 at the $100,000-$150,000 per QALY thresholds. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.

Treatment effectiveness and treatment patterns among rheumatoid arthritis patients after switching from a tumor necrosis factor inhibitor to another medication.

OBJECTIVES: After treatment failure with a tumor necrosis factor inhibitor (TNFi), patients with rheumatoid arthritis (RA) can switch to another TNFi (TNFi cyclers) or to a targeted disease-modifying antirheumatic drug (DMARD) with a non-TNFi mechanism of action (non-TNFi switchers). This study compared treatment patterns and treatment effectiveness between TNFi cyclers and non-TNFi switchers in patients with RA. METHODS: The analysis included a cohort of patients from the Truven Health Analytics MarketScan Commercial database with RA who switched from a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) either to another TNFi or to a non-TNFi targeted DMARD (abatacept, tocilizumab, or tofacitinib) between January 1, 2010 and September 30, 2014. A claims-based algorithm was used to estimate treatment effectiveness based on six criteria (adherence, no dose increase, no new conventional therapy, no switch to another targeted DMARD, no new/increased oral glucocorticoid, and intra-articular injections on <2 days). RESULTS: The cohort included 5,020 TNFi cyclers and 1,925 non-TNFi switchers. Non-TNFi switchers were significantly less likely than TNFi cyclers to switch therapy again within 6 months (13.2% vs 19.5%; P<0.001) or within 12 months (29.7% vs 34.6%; P<0.001) and significantly more likely to be persistent on therapy at 12 months (61.8% vs 58.2%; P<0.001). Non-TNFi switchers were significantly more likely than TNFi cyclers to achieve all six of the claims-based effectiveness algorithm criteria for the 12 months after the initial switch (27% vs 24%; P=0.011). CONCLUSION: Although the absolute differences were small, these results support switching to a non-TNFi targeted DMARD instead of TNFi cycling when patients with RA require another therapy after TNFi failure.