Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma.

BACKGROUND: Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown. METHODS: We randomly assigned 210 patients with oral glucocorticoid-treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed. RESULTS: The percentage change in the glucocorticoid dose was -70.1% in the dupilumab group, as compared with -41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%). CONCLUSIONS: In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214 .).

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

BACKGROUND: Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. METHODS: We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. RESULTS: The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. CONCLUSIONS: In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).

Dupilumab Provides Rapid and Sustained Clinically Meaningful Responses in Adults with Moderate-to-severe Atopic Dermatitis.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.

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.

Reduced Imaging Radiation Exposure and Costs Associated with Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

BACKGROUND: Radiation exposure from diagnostic imaging may increase cancer risk of Crohn's disease (CD) patients, who are already at increased risk of certain cancers. AIM: To compare imaging radiation exposure and associated costs in CD patients during the year pre- and post-initiation of anti-tumor necrosis factor (anti-TNF) agents or corticosteroids. METHODS: Adults were identified from a large US claims database between 1/1/2005 and 12/31/2009 with ≥ 1 abdominal imaging scan and 12 months of enrollment before and after initiating therapy with anti-TNF or corticosteroids. Imaging utilization, radiation exposure, and healthcare costs pre- and post-initiation were examined. RESULTS: Anti-TNF-treated patients had significantly fewer imaging examinations the year prior to initiation than corticosteroid-treated patients. Cumulative radiation doses before initiation were significantly higher for corticosteroid patients compared to anti-TNF patients (22.3 vs. 17.7 millisieverts, P = 0.0083). After therapy initiation, anti-TNF-treated patients had significantly fewer imaging examinations (2.9 vs. 5.2, P < 0.0001) and less radiation exposure (7.4 vs. 15.4 millisieverts, P <0.0001) than corticosteroid-treated patients in the follow-up period. Reductions in imaging costs adjusted for 1000 patient-years after initiation of therapy were - $275,090 and - $121,960 (P = 0.0359) for anti-TNF versus corticosteroid patients, respectively. CONCLUSIONS: This analysis demonstrated that patients treated with anti-TNF agents have fewer imaging examinations, less radiation exposure, and lower healthcare costs associated with imaging than patients treated with corticosteroids. These benefits do not account for additional long-term benefits that may be gained from reduced radiation exposure.

Healthcare Providers Underestimate Patients' Glucocorticoid Use in Crohn's Disease.

BACKGROUND: One of the therapy goals for Crohn's disease (CD) is glucocorticoid-free remission. Studies have shown care setting-specific variations in inflammatory bowel disease (IBD) management. AIMS: The principal objective of this study was to assess concordance between patient-reported and physician-reported outcomes in two different care settings (IBD centers and community practices). METHODS: Data of overall and long-term (≥ 3 months) glucocorticoid, immunosuppressant, and biologics use in participants ≥ 18 years old with a confirmed diagnosis of CD were collected. HCPs were grouped by IBD centers and community practices. Quality of life (using EuroQol 5D [EQ-5D]) and work/activity days lost were assessed. Agreement between patients' and HCPs' responses to survey questions was tested using kappa statistics. RESULTS: Data from 812 patients were examined. Significantly more patients versus HCPs reported oral glucocorticoid use (25.9% vs. 20.8%, κ = 0.735, P < 0.0001). Long-term use of oral glucocorticoids was similar for patients versus HCPs (67.7% vs. 63.8%, κ = 0.598, P = 0.53). Immunosuppressant use was 52.4% vs. 51.1% (κ = 0.784) and biologics use was 49.5% vs. 47.0% (κ = 0.909) for patients vs. HCPs. Patients and HCPs reported greater rates of symptom improvement with vs without biologic therapy (patients: 33.3% vs 16.8%; HCPs: 29.3% vs 13.5%, both P < 0.001). Patients with versus without routine follow-up were less likely to be treated with long-term glucocorticoid monotherapy (10.3% vs. 20.7%, P < 0.01) and had fewer lost work/activity days (5 vs. 8 days, P < 0.05). CONCLUSIONS: Patients reported more oral glucocorticoid use than physicians thought. Routine follow-up and higher rates of biologic use are associated with improvement in disease symptoms and general health among patients with CD.

Risk of Ocular Complications in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis.

PURPOSE: Noninfectious uveitis results in vision loss and ocular complications without adequate treatment. We compared the risk of developing ocular complications between patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis (NIIPPU) and matched controls. DESIGN: Retrospective analysis of insurance claims data (OptumHealth, Eden Prairie, MN; January 1, 1998-March 31, 2012). PARTICIPANTS: Cases 18 to 64 years of age with 2 or more NIIPPU diagnoses (International Classification of Diseases, 9th Revision, Clinical Modification codes) were matched 1:1 by sex, age, region, company, employment status, and index date with controls without uveitis. Patients with an ocular complication during baseline were excluded. METHODS: Continuous eligibility for 6 months or more before the first NIIPPU diagnosis date was required. Risks of ocular complications developing during patients' continuous eligibility in the study period were compared using unadjusted Kaplan-Meier survival analysis to estimate risk of and time to complications and adjusted Cox regression analysis to estimate hazard ratios (HRs). MAIN OUTCOME MEASURES: Percentages of cases and controls who demonstrate ocular complications and 1-, 5-, and 10-year risks and HRs for each complication. RESULTS: Mean age of the 1769 cases and matched controls was 47 years and 47% were men; 302 cases had persistent NIIPPU. During the study period, NIIPPU cases had a higher risk of any ocular complication (P < 0.001); the 5-year risk of any ocular complication was 66% for patients versus 24% for controls. Specifically, NIIPPU patients had greater 5-year risks of glaucoma (20% vs. 9%), cataract (35% vs. 13%), visual disturbance (29% vs. 9%), blindness or low vision (5% vs. 0.5%), retinal detachment (11% vs. 0.8%), and retinal disorder (28% vs. 2%) compared with controls. Hazard ratios indicated greater risks of ocular complications in cases versus controls during the overall observation period (HR, 5.2 for any ocular complication; HR, 4.8 for visual disturbance; HR, 3.2 for cataract; and HR, 2.7 for glaucoma; all P < 0.001). Hazard ratios for persistent cases indicated even greater risks. CONCLUSIONS: Noninfectious intermediate uveitis, posterior uveitis, or panuveitis, particularly persistent disease, is associated with a substantial risk of ocular complications. Optimal treatment initiatives remain imperative to reduce the ocular complication-related burden of NIIPPU.

Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease.

BACKGROUND & AIMS: We investigated whether treatment of active inflammatory bowel disease with biologic agents is associated with a reduced risk of venous thromboembolic events (VTEs) compared with corticosteroid therapy. METHODS: We performed a retrospective analysis of 15,100 adults with inflammatory bowel disease who were identified from the Truven Health MarketScan databases. We analyzed data from patients who received 6 months of continuous medical and prescription coverage before and 12 months after their first diagnosis and had no VTE during the 6 months before they first received biologic or corticosteroid therapy. The outcome assessed was any VTE that occurred during the 12-month follow-up period. A multivariate logistic regression model was used to evaluate the effects of biologic, corticosteroid, and combination therapies (biologics and corticosteroids) on VTE risk. RESULTS: Three hundred twenty-five VTEs occurred during the study period (in 2.25% of patients receiving only corticosteroids, in 0.44% of patients receiving biologics, and in 2.49% of patients receiving combination therapy). Compared with patients receiving only corticosteroids, the odds ratio for VTE in patients receiving only biologics was 0.21 (95% confidence interval, 0.05-0.87) in the multivariate model, and the odds ratio for VTE in patients on combination therapy was 1.01. CONCLUSIONS: Compared with treatment with only a biologic agent, corticosteroid therapy is associated with a nearly 5-fold increase in risk for VTE. Combination therapy with corticosteroids and biologic agents was associated with the same risk for VTE as that of corticosteroids alone. Corticosteroids therefore appear to increase risk for VTE.

Adalimumab therapy is associated with reduced risk of hospitalization in patients with ulcerative colitis.

BACKGROUND & AIMS: Adalimumab is effective for induction and maintenance of remission in patients with moderate to severe ulcerative colitis (UC). We assessed whether adalimumab, in addition to standard UC therapy, reduced the risk for hospitalization (from all causes, from complications of UC, or from complications of UC or the drugs used to treat it) and colectomy in patients with moderate to severe UC compared with placebo. METHODS: Data were combined from patients that received induction therapy (a 160-mg dose followed by an 80-mg dose of adalimumab) or placebo in 2 trials (ULTRA 1 and ULTRA 2; n = 963). The risks of hospitalization and colectomy were compared between groups using unadjusted rates during the 8-week induction period, and patient-year-adjusted rates during 52 weeks. Statistical differences between groups were determined using the χ(2) method and Z score normal approximations. Numbers of hospitalizations were compared using Poisson regression with time offset. RESULTS: Significant reductions in risk of all-cause, UC-related, and UC- or drug-related hospitalizations (by 40%, 50%, and 47%, respectively; P < .05 for all comparisons) were observed within the first 8 weeks of adalimumab therapy compared with placebo. Significantly lower incidence rates for all-cause (0.18 vs 0.26; P = .03), UC-related (0.12 vs 0.22; P = .002), and UC- or drug-related (0.14 vs 0.24; P = .005) hospitalizations were observed during 52 weeks of adalimumab therapy compared with placebo. Rates of colectomy did not differ significantly between patients given adalimumab vs placebo. CONCLUSIONS: In patients with moderate to severe UC, the addition of adalimumab to standard of care treatment reduced the number of hospitalizations for any cause, as well as for UC-related and UC- or drug-related complications, compared with placebo. ClinicalTrials.gov numbers, NCT00385736 and NCT00408629.

Adalimumab induces deep remission in patients with Crohn's disease.

BACKGROUND & AIMS: Patients with moderate to severe ileocolonic Crohn's disease (CD) who received adalimumab induction and maintenance therapy had greater rates of mucosal healing than patients who received placebo after adalimumab induction therapy in a 52-week trial (EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing). We investigated whether this treatment also induced deep remission-a composite clinical and endoscopic end point. METHODS: Rates of deep remission, defined as the absence of mucosal ulceration and CD Activity Index scores less than 150, were compared between patients given continuous adalimumab and those given only induction therapy followed by placebo. We assessed the relationships between deep remission and other outcomes among patients who received adalimumab. The outcomes of patients with deep remission were compared with those of patients with only the absence of mucosal ulceration or only clinical remission. RESULTS: Rates of deep remission were 16% in patients given adalimumab vs 10% in those given placebo (P = .34) at week 12, and 19% vs 0% (P < .001) at week 52. Rates of deep remission were greatest among patients who received adalimumab and had CD for 2 years or less (33% at weeks 12 and 52). At week 52, patients who achieved deep remission at week 12 required significantly fewer adalimumab treatment adjustments, hospitalizations, and CD-related surgeries; had significantly less activity impairment; and had better quality of life and physical function compared with patients not achieving deep remission. Deep remission generally was associated with better outcomes than only an absence of mucosal ulceration; outcomes of patients with deep remission vs only clinical remission were similar. Deep remission was associated with estimated total cost savings of $10,360 (from weeks 12 through 52) compared with lack of deep remission. CONCLUSIONS: In an exploratory study of patients with moderate to severe ileocolonic CD who received adalimumab induction and maintenance therapy, patients achieving deep remission appeared to have better 1-year outcomes than those not achieving deep remission. These findings should be validated in large, prospective trials. ClinicalTrials.gov number: NCT00348283.

Long-Term Effectiveness of Dupilumab in Patients with Atopic Dermatitis: Results up to 3 Years from the RELIEVE-AD Study.

INTRODUCTION: Atopic dermatitis (AD) can require long-term therapy. Few real-world studies have evaluated long-term effectiveness from the patients' perspective. The aim of this study was to evaluate patient-reported outcomes (PROs) during long-term dupilumab treatment. METHODS: Adults with moderate-to-severe AD who initiated dupilumab through the US manufacturer patient support program and participated in RELIEVE-AD (a prospective patient survey study with a 12-month follow-up) were recontacted 30-36 months post-initiation regardless of current dupilumab use. The online questionnaire consisted of PROs, including the Atopic Dermatitis Control Tool (ADCT), use of concomitant AD therapies, satisfaction with current therapy, global change in itch relative to before dupilumab initiation, non-itch skin symptoms (skin pain/soreness, hot/burning feeling, and sensitivity to touch), flares, Dermatology Life Quality Index, sleep problems, and the AD-specific Work Productivity and Activity Impairment Questionnaire. RESULTS: Of 698 patients who initiated dupilumab (baseline) and were recontacted, 425 completed the 30-36-month survey. Significant reductions from baseline were reported in concomitant AD therapy use (P < 0.05); 54.4% reported not using other AD medications vs. 12.8% at baseline. At 30-36 months, all results (non-itch skin symptoms, flares, sleep problems, health-related quality of life work/activity impairment, disease control, and treatment satisfaction) were similar to or incrementally better than the 12-month timepoint, with significant improvements vs. baseline (P < 0.001). Global change in itch was reported as "very much better" by 75.3% of respondents. Adequate disease control (score < 7 on ADCT) was reported by 80.7% of respondents, and 86.8% were satisfied with the treatment. CONCLUSIONS: In clinical practice settings, patient-reported benefits of dupilumab were maintained in survey respondents during long-term treatment up to 36 months while the use of concomitant AD therapies reduced.

Atopic dermatitis (also known as eczema) is a chronic skin disease that can have a profoundly negative effect on patients' quality of life. To control disease symptoms, patients often need long-term treatment. Dupilumab is a treatment that has shown benefits in adults with moderate-to-severe atopic dermatitis (AD) when used in long-term (under 4 years) clinical trials; however, few studies have evaluated patients' experiences of long-term dupilumab treatment outside of a clinical trial setting. This study was conducted to do so: 425 adults with moderate-to-severe AD who received dupilumab through a US manufacturer patient support program filled in an online questionnaire 30­36 months after starting treatment. The questionnaire included items on use of additional AD therapies, AD symptoms, quality of life, disease control, and satisfaction with treatment. Patients' responses showed that, at 30­36 months after starting dupilumab treatment, 54% of patients reported not using any other medications for AD vs. 13% of patients when starting dupilumab treatment. In addition, since starting dupilumab, 75% of patients reported one of the most burdensome AD symptoms, itch, as being "very much better" vs. before starting treatment; 81% reported control of AD symptoms; 85% reported a meaningful improvement in quality of life; and 76% were "extremely" or "very" satisfied with the treatment. In summary, this study showed that long-term dupilumab treatment provides continued improvement in symptoms, treatment satisfaction, disease control, and quality of life in adults with moderate-to-severe AD while reducing the need for other AD treatments. Video abstract: How do patients with atopic dermatitis perceive long-term dupilumab treatment in the real world? (MP4 31888 kb).

Adherence to and Persistence with Adalimumab Therapy among Swedish Patients with Crohn's Disease.

OBJECTIVES: (1) to determine the adherence and persistence rates of adalimumab therapy among Swedish patients with Crohn's disease (CD), and (2) to compare self-administration devices to predict the medication adherence and persistence. METHODS: We conducted a retrospective analysis of the Swedish National Board of Health and Welfare database during a unique time period, when both the pen and the syringe were available. The pen was proposed to indicate a larger extent of internal control, according to health locus of control. Medication adherence was defined as a medication possession ratio (MPR) ≥ 0.8. A patient was considered nonpersistent if the time between any two dispensing records, minus the days of supply dispensed exceeded 180 days. The predictors of adherence were evaluated using a logistic regression, and the predictors of persistence were evaluated using a Cox proportional hazards model. RESULTS: Among the 1083 patients studied, 89% were adherent and 77% were persistent. The patients using the pen and the patients treated in gastroenterology centers were more likely to be adherent and less likely to be nonpersistent. CONCLUSIONS: The adherence rate to adalimumab therapy was 89% and the one-year persistence rate was 70%. The pen and treatment in a gastroenterology center had a positive impact on the adherence and persistence among Swedish patients with CD.

Content validity of a newly developed observer-reported measure for pediatric asthma in children aged 2-5 years.

BACKGROUND: An observer-reported outcome (ObsRO) measure assessing both symptom control and health-related quality of life (HRQoL) in children with asthma younger than 6 years is lacking. The objective of this study was to evaluate the content validity of the Pediatric Asthma Questionnaire (PAQ), a newly developed 6-item ObsRO measure for caregivers of children aged 2-5 years diagnosed with asthma. RESULTS: In-depth, qualitative interviews were conducted with 15 parents or caregivers. The first part of the interview was an open-ended discussion whereby participants were asked to describe their observations of their child's asthma symptoms and HRQoL impacts followed by a cognitive debriefing of a draft version of the PAQ. The most frequently reported symptoms were coughing (n = 15, 100%), wheezing (n = 14, 93%), and trouble breathing (n = 10, 67%). Overall, participants found the PAQ easy to complete and relevant to their child's experience with asthma, with most reporting the instructions, response scales, and recall period for the items to be appropriate. The majority of participants (93%) believed they could accurately report on the items included in the PAQ based on their observations of their child's asthma symptoms and impacts, or reliably get the information from the child's teacher, school, or caregiver when their child was not in their presence. One item was modified based on feedback about the phrase "oral steroids" to clarify modes of administration. A few other minor changes were incorporated into the PAQ following suggestions from participants, including replacing the phrase "how often" with "how many days" in one of the items to improve clarity and overall consistency with the response options. CONCLUSION: Qualitative data support the content validity of the PAQ as a fit-for-purpose and well-understood 6-item observer-reported outcome measure to evaluate both symptoms and asthma-specific HRQoL impacts experienced by pediatric asthma patients aged 2-5 years for use in clinical and real-world studies.

Patient Preferences for Attributes of Biologic Treatments in Moderate to Severe Asthma: A Discrete Choice Experiment Study.

Purpose: Multiple biologics are available for moderate to severe asthma. Given the important relationship between patient engagement in healthcare decision-making and health outcomes, patient preference is an increasingly important consideration. This study elicited patients' preferences for attributes of biologic therapies for moderate to severe asthma. Patient and Methods: A discrete choice experiment (DCE) questionnaire was designed to collect data from an existing survey panel of adults with moderate to severe asthma in the United States. Patients were asked to select their preferred hypothetical treatment from profiles with varying attributes related to efficacy, safety, and administration convenience. Conditional logit regression models were used to quantify patient preferences. Results: Of 301 eligible patients who completed the survey, the mean age was 46.7±15.1 years and 71.8% were female. Patients had asthma for 22.5±16.3 years on average, and most (97.3%) had experienced ≥1 asthma attack in the past 12 months. Among treatment attributes examined, patients most valued the absence of a black box warning for the risk of a life-threatening allergic reaction, effectiveness of reducing severe asthma exacerbations, and improvement in lung function (all p < 0.001). Home administration setting for subcutaneous injections (vs doctor's office/clinic) (p = 0.009) and ability of a biologic to treat additional chronic condition(s) (p < 0.05) were also considered important. Dosing frequency and type of injection device were not significant factors. Conclusion: Patients with moderate to severe asthma valued efficacy and safety over convenience attributes when selecting biologic treatments. Awareness of these preferences can facilitate patient-physician shared decision-making when managing moderate to severe asthma in clinical practice.

Baseline Demographics and Severity and Burden of Atopic Dermatitis in Adult Patients Initiating Dupilumab Treatment in a Real-World Registry (PROSE).

INTRODUCTION: Dupilumab was initially approved in 2017 as the first biologic therapy for atopic dermatitis (AD). We characterized adults with AD initiating dupilumab in a real-world setting in the USA/Canada. METHODS: PROSE is an ongoing, longitudinal, prospective, observational, multicenter registry of patients with AD initiating dupilumab per country-specific prescribing information. We report baseline data (day of first dupilumab injection) for patients enrolled from April 2018 through July 2019. RESULTS: Among 315 patients (mean age 42.5 years, 55.2% female), the median AD duration was 17.0 years; 65.4% reported a history of type 2 inflammatory comorbidities (e.g., allergic rhinitis, asthma), and 93.3% reported treatment(s) for AD in the previous year, including topical corticosteroids (90.8%), systemic corticosteroids (36.2%), and nonsteroidal systemic therapies (14.0%). In total, 89.2% had an Overall Disease Severity score of 3 (moderate) or 4 (severe). Other mean disease severity scores included the following: Eczema Area and Severity Index 16.9 (range 0-72), body surface area affected 26.8%, Patient-Oriented Eczema Measure 18.5 (range 0-28), Dermatology Life Quality Index 12.7 (range 0-30), and pruritus Numerical Rating Scale score 6.9 (range 0-10). CONCLUSION: Patients initiating dupilumab have longstanding moderate-to-severe AD with significant disease burden and frequent type 2 comorbidities. GOV IDENTIFIER: NCT03428646.

Dupilumab Treatment Reduces Hospitalizations in Adults With Moderate-to-Severe Atopic Dermatitis.

BACKGROUND: Refractory disease, flares, or infections in atopic dermatitis (AD) can lead to hospitalizations. OBJECTIVE: To compare hospitalization rates among adults with moderate-to-severe AD treated with dupilumab versus control. METHODS: Data from 7 randomized, placebo-controlled trials of dupilumab (300 mg every 2 weeks [q2w] and/or weekly [qw]; with or without topical corticosteroids) were analyzed. RESULTS: Patients in the dupilumab 300 mg q2w, qw, and combined dupilumab (q2w and qw; n = 1,841) groups compared with patients in the control group (n = 1,091) had lower rates of all-cause hospitalizations (5.8, 2.7, and 3.8 events, respectively, vs 9.0 events per 100 patient-years [PY]; all P < .05 [49%, 71%, and 62% risk reduction, respectively]); AD-related hospitalizations (2.0, 0.4, 1.0 events vs 4.1 events per 100 PY; P < .05 for qw and dupilumab combined [91% and 79% risk reduction, respectively]); as well as reduced overall duration of AD-related hospitalization (10.9, 7.3, and 8.6 d vs 38.9 d per 100 PY). CONCLUSIONS: Among adults with moderate-to-severe AD, treatment with dupilumab versus control was associated with significant reductions in all-cause and AD-related hospitalization rates, and shorter duration of AD-related hospitalization.

Development, Psychometric Validation and Responder Definition of Worst Itch Scale in Children with Severe Atopic Dermatitis.

INTRODUCTION: Itch associated with atopic dermatitis (AD) has a profoundly negative effect on patients of all ages. Therefore, itch is a main target for AD therapeutic approaches, and treatments are perceived as beneficial when they achieve an itch reduction. In the absence of a validated scale for children aged 6-11 years that is suitable for assessing itch intensity in clinical trial settings, the Worst Itch Scale was developed. METHODS: Qualitative interviews, comprising concept elicitation and cognitive debriefing, were conducted to develop and evaluate the content validity of the Worst Itch Scale. Psychometric assessments used data from the LIBERTY AD PEDS phase 3 trial of dupilumab in patients aged 6-11 years with severe AD. These included test-retest reliability, construct validity, known-groups validity and responsiveness. Thresholds for clinically meaningful change were defined using anchor- and distribution-based methods. RESULTS: The Worst Itch Scale consisted of two items asking about 'worst itching' experienced 'last night' and 'today'. Worst Itch Scale scores showed large, positive correlations with existing patient-reported outcome (PRO) measures of itch, and weaker correlations with clinician-reported outcome (ClinRO) measures assessing objective signs of AD. Improvements in Worst Itch Scale scores were highly correlated with improvements in other itch PROs and moderately correlated with improvements in ClinROs. The responder definition based on the primary anchor, a 1-point improvement in the Patient Global Impression of Disease, was 2.84. Supportive anchors produced response estimates ranging from 2.43 to 4.80 points. CONCLUSIONS: The Worst Itch Scale is a fit-for-purpose (e.g. well-defined, reliable, responsive and valid) scale for evaluating worst itch intensity in children aged 6-11 years with severe AD. The within-patient threshold for defining a clinically meaningful response was a ≥ 3-4-point change in the Worst Itch Scale score. TRIAL REGISTRATION: NCT03345914. Video: How can we reliably assess itch intensity in children 6-11 years with severe atopic dermatitis in clinical trial settings?