Dupilumab, an anti–IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab ...reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists.
To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR).
A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L).
Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, −5.98; 95% CI, −10.45 to −1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, −0.60; 95% CI, −0.96 to −0.25; runny nose, −0.67; 95% CI, −1.04 to −0.31; sneezing, −0.55; 95% CI, −0.89 to −0.21; postnasal discharge, −0.49; 95% CI, −0.83 to −0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (−1.82; 95% CI, −6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo.
Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.
Conducting and analyzing clinical studies of cough and cold medications is challenging due to the rapid onset and short duration of the symptoms. The use of Internet-based surveillance tools is a new ...approach in clinical studies that is gradually becoming popular and may become a useful method of recruitment. As part of an initiative to assess the safety and efficacy of cough and cold ingredients in children 6-11 years of age, a surveillance program was proposed as a means to identify and recruit pediatric subjects for clinical studies.
The objective of the study was to develop an Internet-based surveillance system and to assess the feasibility of using such a system to recruit children for common cold clinical studies, record the natural history of their cold symptoms, and determine the willingness of parents to have their children participate in clinical studies.
Healthy potential subjects were recruited via parental contact online. During the 6-week surveillance period, parents completed daily surveys to record details of any cold symptoms in their children. If a child developed a cold, symptoms were followed via survey for 10 days. Additional questions evaluated the willingness of parents to have their children participate in a clinical study shortly after onset of symptoms.
The enrollment target of 248 children was reached in approximately 1 week. Children from 4 distinct geographic regions of the United States were recruited. Parents reported cold symptoms in 163 children, and 134 went on to develop colds. The most prevalent symptoms were runny nose, stuffed-up nose, and sneezing. The most severe symptoms were runny nose, stuffed-up nose, and sore/scratchy throat. The severity of most symptoms peaked 1-2 days after onset. Up to 54% of parents expressed willingness to bring a sick child to a clinical center shortly after the onset of symptoms. Parents found the Internet-based surveys easy to complete.
Internet-based surveillance and recruitment can be useful tools to follow colds in children and enroll subjects in clinical studies. However, study designs should account for a potentially high dropout rate and low rate of adherence to study procedures.
Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions.
The prospective, observational EUROSTAD study ...enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics.
A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean standard deviation disease severity/burden measures were high: Investigator's Global Assessment (3.1 0.8), Eczema Area and Severity Index (16.2 10.9), Peak Pruritus Numerical Rating Scale (5.5 2.5), sleep impairment Visual Analog Scale (49.8 31.6) scores, and time lost from work (4.1 13.7 days/year) or usual activities (16.8 38.7 days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale.
Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies.
The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of ...patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting.
Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months.
288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled.
The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.
IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disease often associated with atopic comorbidities and has significant impact on children and their families. There is a lack of ...robust and longitudinal long-term data on disease characteristics and typical clinical practice with currently available treatments in children with moderate-to-severe AD. Hence, an observational study is needed to evaluate AD characteristics and progression in paediatric patients with moderate-to-severe AD.Methods and analysisPediatric Study in Atopic Dermatitis (PEDISTAD) is a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe AD who are currently receiving systemic or topical treatment and whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not medically advisable. 1300 children at 100–150 sites in approximately 20 countries worldwide will be enrolled and followed for 5 years. AD therapy is at the discretion of the investigator. Data collected will include: AD disease characteristics and comorbidities; current therapy for AD and initiation of new treatments/changes in current treatment; patient-reported/caregiver-reported outcomes; days missed from school/work for the patient/caregiver; healthcare professional visits; safety and biomarkers.Ethics and disseminationThis study is conducted in accordance with the principles established by the 18th World Medical Assembly and all subsequent amendments and the guidelines for Good Epidemiology Practice. Each individual country assures that ethics approval has been received and local regulatory requirements are met. Ethics approval has been obtained in all countries currently participating in PEDISTAD. Study data will be disseminated in manuscripts submitted to peer-reviewed medical journals as well as in abstracts submitted to congresses and in the resulting posters and presentations.Trial registration numberNCT03687359; pre-results.
Analgesic effects of ibuprofen immediate‐release/extended‐release (IR/ER) 600‐mg tablets were evaluated in 2 randomized, double‐blind, placebo‐controlled dental pain studies. Patients 16–40 years old ...with moderate–severe pain following third‐molar extraction received single‐dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation SD) time‐weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0–12 hours and ‐0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8–12 hours (all P < .001 vs placebo). In study 2 (n = 106), mean (SD) time‐weighted sum of pain relief and pain intensity difference scores were 18.2 (20.0) versus 41.5 (21.0) at 0–12 hours and 10.3 (12.0) versus 18.4 (12.1) at 8–12 hours for placebo versus ibuprofen IR/ER, respectively (P < .001 for both); efficacy was sustained over each of the four 12‐hour dosing intervals with ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses.
Two blinded single-dose studies randomized children 6 months to 11 years old with fever to receive ibuprofen (IBU) pediatric suspension 7.5 mg/kg or acetaminophen (APAP) suspension 10 to 15 mg/kg. ...The primary efficacy parameter was time-weighted sum of temperature differences (TWSTD) from baseline through 8 hours for each study. Secondary end points included TWSTD from baseline through 6 hours, time to onset and duration of temperature control, and proportion with temperature control. Studies were pooled for post hoc analyses of efficacy and adverse event end points. The primary efficacy parameter significantly favored IBU over APAP in study 1 and the pooled analysis (both P < .001), but was not significant in study 2. Onset of temperature control significantly favored IBU in study 2 (P = .007). Individual and pooled secondary efficacy outcomes supported significant advantages (P < .05) of IBU over APAP. IBU pediatric suspension provided greater temperature reduction versus acetaminophen in febrile children, with a comparable safety profile.
Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, ...was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, C
was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CL
and V
/F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t
existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar C
and AUC.
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