Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial

Reich, Kristian; Teixeira, Henrique D.; Bruin‐Weller, Marjolein de; Bieber, Thomas; Soong, Weily; Kabashima, Kenji; Werfel, Thomas; Zeng, Jiewei; Huang, Xin; Hu, Xiaofei; Hendrickson, Barbara A.; Ladizinski, Barry; Chu, Alvina D.; Silverberg, Jonathan I.

doi:10.1016/s0140-6736(21)00589-4

Cited by 220 publications

(206 citation statements)

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“…The results of thoracic US fairly correlate with those of chest CT, and several authors have shown that thoracic US is an accurate noninvasive tool for diagnosis, assessment of disease severity, and monitoring of Covid-19 patients [ 30 , 31 ]. Our findings appear consistent with previous studies showing the persistence of lung abnormalities in a high percentage of Covid-19 patients undergoing postacute follow-up CT chest imaging [ 10 , 32 ]. The data on the performance of thoracic US in the postacute phase of Covid-19 are scant.…”

Section: Discussionsupporting

confidence: 93%

“…Namely, in addition to the onset of postdischarge insomnia, about one-fifth of the patients reported anxiety and depression. This finding is in keeping with the previous studies, which reported new-onset psychiatric disorders, such as anxiety, depression, and post-traumatic stress disorder with widely varying prevalence rates [ 10 , 15 – 17 ].…”

Section: Discussionsupporting

confidence: 93%

“…The most common symptoms were fatigue (42.4%) and dyspnea (37.3%). Similar data were recently reported by four studies evaluating COVID-19 patients 60 [ 6 , 7 ], 90 [ 8 ], and 110 days [ 9 ] after hospital discharge and by a large Chinese study performed 6 months after hospital discharge [ 10 ]. Our data suggest that COVID-19 has a significant impact on patient mental well-being.…”

Section: Discussionsupporting

confidence: 87%

“…At present, the available data from follow-up studies are limited. Preliminary analyses indicate that a substantial subset patients continue to complain of persistent symptoms after several months [ 6 – 10 ]. In some cases, organ damage is found, especially in the lungs [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Preliminary analyses indicate that a substantial subset patients continue to complain of persistent symptoms after several months [ 6 – 10 ]. In some cases, organ damage is found, especially in the lungs [ 10 – 12 ]. To identify and manage the postacute sequelae of COVID-19 still present 3–6 months after hospital discharge, we implemented an outpatient post-COVID-19 follow-up program.…”

Section: Introductionmentioning

confidence: 99%

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COVID-19: persistence of symptoms and lung alterations after 3–6 months from hospital discharge

et al. 2021

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Purpose Few data are currently available on persistent symptoms and late organ damage in patients who have suffered from COVID-19. This prospective study aimed to evaluate the results of a follow-up program for patients discharged from a nonintensive COVID-19 ward. Methods 3–6 months after hospital discharge, 59 of 105 COVID-19 patients (31 males, aged 68.2 ± 12.8 years) were recruited in the study. Forty-six patients were excluded because of nontraceability, refusal, or inability to provide informed consent. The follow-up consisted of anamnesis (including a structured questionnaire), physical examination, blood tests, ECG, lower limb compression venous ultrasound (US), thoracic US, and spirometry with diffusion lung capacity for carbon monoxide (DLCO). Results 22% of patients reported no residual symptoms, 28.8% 1 or 2 symptoms and 49.2% 3 or more symptoms. The most frequently symptoms were fatigue, exertional dyspnea, insomnia, and anxiety. Among the inflammatory and coagulation parameters, only the median value of fibrinogen was slightly above normal. A deep vein thrombosis was detected in 1 patient (1.7%). Thoracic US detected mild pulmonary changes in 15 patients (25.4%), 10 of which reported exertional dyspnea. DLCO was mildly or moderately reduced in 19 patients (37.2%), 13 of which complained of exertional dyspnea. Conclusion These results highlight that a substantial percentage of COVID-19 patients (77.8%) continue to complain of symptoms 3–6 months after hospital discharge. Exertional dyspnea was significantly associated with the persistence of lung US abnormalities and diffusing capacity alterations. Extended follow-up is required to assess the long-term evolution of postacute sequelae of COVID-19.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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COVID-19: persistence of symptoms and lung alterations after 3–6 months from hospital discharge

et al. 2021

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Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis

et al. 2021

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IMPORTANCE Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.OBJECTIVE To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.DESIGN, SETTING, AND PARTICIPANTS Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population.INTERVENTIONS Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURESThe primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTSOf 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.CONCLUSIONS AND RELEVANCE During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dup...

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Systemic Immunomodulatory Treatments for Atopic Dermatitis

et al. 2022

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IMPORTANCE Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head. OBJECTIVE To compare reported measures of efficacy and assessments of safety in clinical trials of systemic treatments for atopic dermatitis in a living systematic review and network meta-analysis. DATA SOURCES The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of EczemA Trials database, and trial registries were searched through June 15, 2021. STUDY SELECTION Randomized clinical trials examining 8 or more weeks of treatment with systemic immunomodulatory medications for moderate-to-severe atopic dermatitis were included after screening titles, abstracts, and papers in duplicate. DATA EXTRACTION AND SYNTHESIS Data were abstracted in duplicate. Bayesian network meta-analyses and assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed. The updated analysis was completed from June to December 2021.MAIN OUTCOMES AND MEASURES Outcomes include change in Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numeric Rating Scales (PP-NRS).RESULTS Since October 2019, 21 new studies were added, for a total of 60 trials with 16 579 patients. Up to 16 weeks of treatment in adults, abrocitinib, 200 mg daily (mean difference [MD], 2.2; 95% credible interval [CrI], 0.2-4.0; high certainty) and upadacitinib, 30 mg daily (MD, 2.7; 95% CrI, 0.6-4.7; high certainty) were associated with reduced EASI slightly more than dupilumab, 600 mg then 300 mg every 2 weeks. Abrocitinib, 100 mg daily (MD, −2.1; 95% CrI, −4.1 to −0.3; high certainty), baricitinib, 4 mg daily (MD, −3.2; 95% CrI, −5.7 to −0.8; high certainty), baricitinib, 2 mg daily (MD, −5.2; 95% CrI, −7.5 to −2.9; high certainty) and tralokinumab, 600 mg then 300 mg every 2 weeks (MD, −3.5; 95% CrI, −5.8 to −1.3; high certainty) were associated with reduced EASI slightly less than dupilumab. There was little or no difference between upadacitinib, 15 mg daily, and dupilumab (MD, 0.2; 95% CrI, −1.9 to 2.2; high certainty). The pattern of results was similar for POEM, DLQI, and PP-NRS. CONCLUSIONS AND RELEVANCEIn this systematic review and meta-analysis, abrocitinib, 200 mg; and upadacitinib, 30 mg daily, were associated with slightly better scores than dupilumab, and upadacitinib, 15 mg daily, was associated with similar scores to dupilumab. Abrocitinib, 100 mg daily, baricitinib, 4 mg and 2 mg daily, and tralokinumab, 300 mg, every 2 weeks were associated with slightly worse scores.

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Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial

Cited by 220 publications

References 28 publications

COVID-19: persistence of symptoms and lung alterations after 3–6 months from hospital discharge

COVID-19: persistence of symptoms and lung alterations after 3–6 months from hospital discharge

Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis

Systemic Immunomodulatory Treatments for Atopic Dermatitis

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