Search

Importance: The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available., Objective: To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks., Design, Setting, and Participants: The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023., Interventions: Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily., Main Outcomes and Measures: Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline., Results: From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose., Conclusions and Relevance: In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks., Trial Registrations: Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.

Introduction: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD., Methods: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up., Results: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab., Conclusions: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab., Trial Registration: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397)., (© 2024. The Author(s).)

Introduction: Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes., Methods: A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation., Results: Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24., Conclusions: For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg., (© 2024. The Author(s).)

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks., Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed., Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo ( p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS., Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Background: In patients with moderate-to-severe atopic Dermatitis® (AD), greater skin clearance and itch reduction are associated with more pronounced improvements in quality of life (QoL). Objective : To characterize the aggregate response benefit with upadacitinib versus dupilumab or placebo in patients with moderate-to-severe AD. Methods : Degree of skin clearance and itch response in 3 phase 3 studies (Heads Up [NCT03738397] and Measure Up 1/2 [integrated; NCT03569293/NCT03607422]) were assessed by the Eczema Area and Severity Index (EASI) and Worst Pruritus Numerical Rating Scale (WP-NRS), respectively, using mutually exclusive categories. The aggregate response benefit with upadacitinib over dupilumab or placebo was determined by summing incremental differences for each EASI or WP-NRS category across the full distribution of patient responses. Results : Comparisons across EASI improvement threshold distributions, EASI severity levels, and WP-NRS categories demonstrated an aggregate response benefit favoring upadacitinib over dupilumab as early as week 4 and continuing at weeks 16 and 24. Similar trends were observed for upadacitinib 15 and 30 mg versus placebo. Conclusions : The aggregate response benefit in skin clearance and itch reduction favored upadacitinib 30 mg over dupilumab and upadacitinib 15 or 30 mg over placebo. These benefits may translate to overall greater improvements in patient QoL.

Introduction: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks., Methods: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment)., Results: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16., Conclusions: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD., Trial Registration: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422., (© 2024. The Author(s).)

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis., Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis., Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16., Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes., Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52., Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018)., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD), a relapsing, inflammatory skin disease, is associated with pruritus that can negatively affect patients' quality of life. Understanding the burden of AD is critical for informing and tailoring treatment and disease management to improve patient outcomes. This study characterized global treatment patterns and the clinical, psychosocial and economic burden of moderate-to-severe AD., Methods: MEASURE-AD was a cross-sectional 28-country study in patients with physician-confirmed moderate-to-severe AD who were either receiving or eligible for systemic therapy for AD. Patients ≥12 years were enrolled between December 2019 and December 2020 while attending routine office or clinic visit. Primary outcomes included Worst Pruritus Numeric Rating Scale (WP-NRS; range: 0-10) and Dermatology Life Quality Index (DLQI; range: 0-30) and Children's DLQI (CDLQI; range: 0-30). Secondary outcomes included physician- and patient-reported clinical, psychosocial and economic burden., Results: Of the 1591 patients enrolled, 1558 (1434 adults and 124 adolescents) fulfilled all patient selection criteria and were included in this analysis. Almost all patients (98.4%) in the total population were using AD medications and more than half (56%) were receiving systemic medication (15% systemic monotherapy). The most used systemic therapies were dupilumab (56.3%), systemic glucocorticoids (18.1%) and methotrexate (16.2%). Mean WP-NRS was 5.3 in the total population, and most patients (≥55%) reported moderate-to-severe pruritus (WP-NRS ≥4). Mean DLQI was 10.8 and mean CDLQI was 9.6. Secondary endpoints demonstrated substantial clinical, psychosocial, and economic burden of disease. Subgroup analysis demonstrated that patients receiving systemic therapy had lower disease burden than those not taking systemic medications., Conclusions: While systemic therapy lowers overall disease burden, patients with moderate-to-severe AD continue to have substantial multidimensional disease burden and uncontrolled disease. Overall, there is a need for effective disease management, including effective treatments that improve patients' psychosocial outcomes and reduce the economic burden of AD., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized., Objectives: Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate-to-severe AD and evaluate the kinetics of recovery on rescue treatment., Methods: Data from a phase 2b randomized, placebo-controlled trial (NCT02925117) of upadacitinib in patients with moderate-to-severe AD were analysed. Patients were randomized 1:1:1:1 to receive upadacitinib 7.5 mg, 15 mg, 30 mg or placebo, and then at Week 16, patients were re-randomized 1:1 to receive the same dose of upadacitinib (upadacitinib 30 mg for patients initialized to placebo) or placebo. From Week 20, those who experienced loss of response defined as Eczema Area and Severity Index <50% improvement from baseline (EASI 50) received rescue treatment with upadacitinib 30 mg., Results: Patients who withdrew from upadacitinib experienced a rapid loss of skin clearance response, while those who switched from placebo to upadacitinib gained response. Loss of skin clearance response occurred within 4 weeks and worsening of itch occurred within 5 days. In patients who originally received placebo or a lower dose of upadacitinib leading to a loss of EASI response, rescue treatment with upadacitinib 30 mg resulted in rapid recovery or improvement of both skin and itch responses; most patients who were re-randomized to placebo achieved EASI 75 and IGA 0/1 by 8 weeks of rescue treatment. No new safety risks were observed., Conclusions: Continuous treatment with upadacitinib is suggested to maintain skin clearance and antipruritic effects., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD., Methods: Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181-1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis., Results: The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes., Conclusions: Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient's personalized treatment plan., (© 2023. The Author(s).)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD., Methods: Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12-75 years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups., Results: Of the 882 participants included in the psychometric analyses, the majority were adults ( n  = 769, 87.2%), male ( n  = 536, 60.8%), and white ( n  = 630, 71.4%). Multi-item scores from the ADerm-SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clinically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD., Conclusions: These results provide evidence that the scores produced by the Worst Pruritus NRS, ADerm-SS, and ADerm-IS are reliable and construct-valid when completed by adults and adolescents with moderate to severe AD in a clinical trial setting. The results presented here expand upon the previous qualitative evidence of these tools and provide further support for their use in future clinical studies. While results are specific to clinical trials, next steps would be to evaluate the use of these questionnaires in clinical practice. This can provide clinicians and dermatologists a window into the patient's disease experience outside of the clinic, aid in shared decision making, and support a patient-centric approach to management of moderate to severe AD.

Background: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib., Objectives: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD., Methods: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated., Results: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin., Conclusions: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients., Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up)., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed., Objective: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab., Methods: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis., Results: Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed., Limitations: Open-label study design., Conclusions: Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed., Competing Interests: Conflicts of interest Dr Blauvelt has served as a speaker (received honoraria) for AbbVie, Arcutis, Bristol Myers Squibb, Eli Lilly, Pfizer, Regeneron, Sanofi, and UCB. He has served as a scientific advisor (received honoraria) for AbbVie, Abcentra, Affibody, Aligos, Almirall, Alumis, Amgen, Anaptysbio, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Dermavant, EcoR1, Eli Lilly, Escient, Evelo, Evommune, Forte, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, LEO Pharma, Merck, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, TLL Pharmaceutical, TrialSpark, UCB Pharma, Vibliome, and Xencor. He has been a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Eli Lilly, Evelo, Evommune, Galderma, Incyte, Janssen, LEO Pharma, and Merck. Dr Prajapati has served as an investigator for AbbVie, Amgen, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, UCB Pharma, and Valeant. He has served as a consultant, advisor and/or speaker for AbbVie, Actelion, Amgen, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, LEO Pharma, L’Oreal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB Pharma, and Valeant. Dr Laquer has received honoraria as a consultant from AbbVie, Allos, Aqua, Biogen, Celgene, Eli Lilly, Galderma, Intraderm, LEO Pharma, Mayne, Novartis, and Pfizer. She has served as an investigator for AbbVie, Aiviva, Amgen, Arcutis, Arena, Bellus, Biofrontera, Bristol Meyers Squibb, Cara, Dermavant, Forte, Galderma, Incyte, Kiniksa, Eli Lilly, LEO Pharma, Novan, Novartis, Ortho Dermatologics, Pfizer, Sun Pharma, and UCB. Dr Fischer has served as a principal investigator for AbbVie, UCB, and Eli Lilly. Dr Eisman has served on the Dermatology Advisory Alopecia Areata Board for Eli Lilly and is or has been an investigator in clinical trials for Pfizer Inc, AbbVie, Arena Pharmaceuticals, Boston Pharmaceuticals, Bristol Myers Squibb, Botanix Pharmaceuticals, Dermira, Eli Lilly, Evelo Biosciences, Immunic Therapeutics, Jansen, Kobiolabs, Kymab Ltd, LEO Pharma, Novartis, TEVA Pharmaceuticals, Tigermed Pharmaceuticals, Suzhou Connect Biopharmaceuticals, and Regeneron Pharmaceuticals. Dr Eyerich has served as a speaker, investigator, and/or advisor for AbbVie, Almirall, Berlin Chemie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Hexal, Galapagos, Janssen, Eli Lilly, Pfizer, Novartis, Sanofi, and UCB Pharma. Drs Ladizinski, Hu, Wu, Calimlim, Kaplan, Y Liu, Teixeira, and J Liu are full-time employees of AbbVie and may hold AbbVie stock or stock options., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population., Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents., Design, Setting, and Participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021., Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up)., Main Outcomes and Measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points)., Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate., Conclusions and Relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile., Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Background: It is not fully understood how different degrees of improvements in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient-reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, anxiety, depression, quality of life (QoL), and work productivity., Objectives: This post hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL., Methods: Data from three randomized, double-blind, placebo-controlled, phase 3 trials in adults and adolescents with moderate to severe atopic dermatitis (Measure Up 1, Measure Up 2, and AD Up) were included. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30 mg) or placebo once daily (alone or in combination with topical corticosteroids). The mean percentage improvement from baseline to week 16 and percentage of patients achieving responses at week 16 were summarized by the Eczema Area and Severity Index (EASI) and validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) response level categories., Results: A total of 2392 patients from the three trials were included in the analysis. Increasingly greater mean percentage improvement and proportion of patients achieving response was observed at higher clinical response levels (i.e., stepwise pattern). Mean percentage improvement and proportion of patients achieving response exceeded 69% and 70% at EASI ≥ 90 and vIGA-AD 0/1, respectively, for most PROs including Worst Pruritus Numeric Rating Scale, Patient Oriented Eczema Measure, and Dermatology Life Quality Index., Conclusions: Greater degrees of clinical responses are related to more robust improvements across multiple dimensions impacted by AD, including itch, skin pain, sleep, anxiety, depression, and QoL., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation., Methods: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate-severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups., Results: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1-2 with minimal, 3 with mild, 4-7 with moderate, and 8-10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3-6 with moderate, and 7-10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0-1 was associated with absent, 2-11 with minimal, 12-22 with mild, 23-47 with moderate, and 48-70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1-3 with minimal, 4-6 with mild, 7-20 with moderate, and 21-30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1-2 with minimal, 3-7 with mild, 8-25 with moderate, and 26-40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1-2 with minimal, 3-8 with mild, 9-22 with moderate, and 23-30 with severe., Conclusions: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice., Trial Registration Number: NCT03568318., (© 2022. The Author(s).)

Introduction: Real-world data on the epidemiology and economic burden of atopic dermatitis (AD) are limited. Here we describe the epidemiology and economic burden of AD using electronic healthcare data from Israel., Methods: A retrospective study was performed using the Maccabi Healthcare Services database. AD incidence in 2008-2017 and point prevalence (AD prev ) on 31 December 2017 were described using diagnosis codes for overall patients, and sex and age subgroups. For AD prev , severity was defined using recently dispensed treatments for AD. Annual healthcare resource utilization in AD prevalent patients was compared with non-AD matched controls using generalized linear modelling. Direct annual costs were estimated also., Results: AD incidence was 7.0/1000 person-years; overall prevalence was 4.4% (female patients 4.5%, male patients 4.3%; age 0 to less than 6 months, 0.9%; 6 months to less than 12 years, 11.0%; 12 to less than 18 years, 5.8%; 18 years or older, 2.2%). Among AD prev (n = 94,483), mild, moderate, and severe AD comprised 57.7%, 36.2%, and 6.1% (adults 43.8%, 46.3%, 9.9%), respectively. Dermatologist and allergist visits and hospitalization rates (at least one) were 40.7%, 6.6%, and 3.8% in 2017. Compared with controls, overall and moderate-to-severe AD were associated with 36% and 52% increases in annual per-person costs (incremental costs $126 and $190)., Conclusions: AD epidemiology in Israel is comparable with other real-world database studies. AD imposes an economic burden that increases with disease severity., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD., Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis., Results: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily., Discussion: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment., Conclusion: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12-16 weeks of therapy in AD., (© 2022. The Author(s).)

Importance: Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown., Objective: To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis., Design, Setting, and Participants: Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2)., Interventions: Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner., Main Outcomes and Measures: Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed., Results: Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals., Conclusions and Relevance: In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks., Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).

Aims: Although pruritus is a hallmark feature of atopic dermatitis, no study has investigated the associated impact of pruritus, due to atopic dermatitis in Japan. The study aimed to evaluate the real-life burden of atopic dermatitis by pruritus severity in adult Japanese patients. The primary objective was to assess the correlation between pruritus severity and work productivity and activity impairment. A secondary objective was to characterize the impact of pruritus on quality of life and to evaluate the burden of symptoms severity and frequency., Materials and Methods: A cross-sectional internet-based survey was conducted. Eligible patients were currently employed and working adults with atopic dermatitis for at least 6 months. Stratification on pruritus severity assessed by the Worst Pruritus Numerical Rating Scale at the screening was performed to ensure that different severity groups are represented. Correlations were assessed using Spearman's rank-order correlation coefficient. Multivariate regression analyses were performed to assess the impact of pruritus severity on work productivity and quality of life., Results: The study analyzed 370 patients. Pruritus severity significantly correlated with work impairment (Rho = 0.622, P value (H0: Rho > 0.5) <.001). A greater pruritus severity was associated with greater work productivity and activity impairment and a greater impact on quality of life, sleep, emotional state, and everyday activities. Patients with a greater pruritus severity carried a higher economic burden of treatment and were more often not satisfied with the received therapy., Limitations: All data were self-reported by patients via an online survey, which is associated with the risk of misclassification for diagnosis, recall bias, and limited participation of patients., Conclusions: The study provides evidence that pruritus is associated with the overall disease burden and impacts many important life aspects of patients with atopic dermatitis in Japan.

Hidradenitis Suppurativa Clinical Response (HiSCR), is a validated tool that has been used to assess the efficacy of adalimumab among patients with hidradenitis suppurativa. We evaluated the clinical meaning of HiSCR by relating it to patient-reported outcomes to give further context to its achievement in a post hoc analysis of integrated data from two phase 3 clinical trials (PIONEER I and II). Pooling placebo and active treatment arms, 39% of patients (245/629) achieved HiSCR at week 12. Irrespective of treatment, significantly (p <0.05) more HiSCR responders than non-responders experienced clinically meaningful improvement in Dermatology Life Quality Index (60.5% vs 30.4%), Pain Numeric Rating Scale (46.9% vs 19.9%), hidradenitis suppurativa quality of life (49.4% vs 26.9%), work-related performance (52.6% vs 37.7%), and non-work-related performance (59.5% vs 33.3%). Clinically meaningful outcomes in hidradenitis suppurativa are more likely to be attained in patients achieving HiSCR level improvement.

The current emphasis on preventive health care and wellness services suggests that measures of skills and competencies needed to effectively navigate the health care system need to be better defined. We take an expanded perspective of health literacy and define it as a set of skills used to organize and apply health knowledge, attitudes and practices relevant when managing one's health environment. It is an emerging area of inquiry especially among adults and those with chronic conditions; however, it has been less studied among adolescent populations. To begin operationalizing this concept in a manner appropriate for teens in a health systems context, we explored knowledge, attitudes and practices related to health and preventive health care in 12 focus groups with publicly insured adolescents (N = 137), aged 13-17 years, as well as eight key informant interviews with physicians who serve publicly insured teens. Five dimensions emerged that provide a preliminary framework for an expanded definition of health literacy among adolescents. These include: (i) navigating the system, (ii) rights and responsibilities, (iii) preventive care, (iv) information seeking and (v) patient-provider relationship. This robust definition of health literacy contextualizes the concept in a health environment where individuals must be informed and skilled health care consumers.

Objective: To evaluate the impact of uncontrolled asthma on the absenteeism and health-related quality of life (HRQOL) of adults and children with asthma and the caregivers of pediatric patients., Patients and Methods: Patient information was obtained from datasets maintained by National Jewish Health for this cross-sectional study. Participants in the study were 12 years of age or older. Participants younger than 18 years had their information provided by caregivers. Caregivers also provided 6 months of absenteeism and QOL data. Participants were classified as having uncontrolled asthma based on a treatment and symptom guideline-based algorithm. Absenteeism was assessed from the self-reported number of work or school days missed due to asthma during the previous 6 months. HRQOL among adults was measured using the validated Marks Asthma Quality of Life Questionnaire (Marks-AQLQ) and among caregivers using the validated Pediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ). To account for the positive skew in absenteeism data, a zero-inflated Poisson regression model was used to compare group differences. HRQOL was analyzed for adults and caregivers using the Wilcoxon-Mann-Whitney test., Results: A total of 15,149 patients met the inclusion criteria for the study and were included in the analysis. Adults with uncontrolled asthma and caregivers of children with uncontrolled asthma reported significantly higher absenteeism than their controlled counterparts: 43% vs 24% adults reported missing days of work, with a median 6 days vs 3 days missed; 31% vs 16% of caregivers reported missing days of work, with 4 days vs 2 days missed; and caregivers reported that more than 70% vs 45% pediatric patients missed school, with a median of 6 days vs 4 days missed (uncontrolled vs controlled asthma, respectively). Adult uncontrolled asthmatics and caregivers of uncontrolled pediatric patients had significantly lower HRQOL as indicated by the Marks-AQLQ (scores 1.5 points higher, p < 0.001) and PACQLQ (scores < 0.5 points lower, p < 0.001), respectively., Conclusions: Uncontrolled asthma has far-reaching impact on the productivity and quality of life of asthma patients and their caregivers. Proper assessment, treatment, and disease management to improve asthma control may reduce the impact of uncontrolled asthma on asthmatic adults, children, and the caretakers of pediatric asthmatic patients.