JAMA Dermatology

<jats:p>This case report describes a patient with refractory porokeratosis ptychotropica who experienced substantial improvement in symptoms with upadacitinib treatment.</jats:p>

Treatment of porokeratosis ptychotropica with a topical combination of cholesterol and simvastatin.

JAMA Dermatol

Safety and efficacy of topical simvastatin plus cholesterol cream versus topical simvastatin cream alone for porokeratosis ptychotropica: a randomized, single-blind, split-body, placebo-controlled, investigator-initiated trial.

J Am Acad Dermatol

Genomic variations of the mevalonate pathway in porokeratosis.

Elife

Clonal expansion of second-hit cells with somatic recombinations or C&gt;T transitions form porokeratosis in MVD or MVK mutant heterozygotes.

J Invest Dermatol

The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

Cell

Targeted anti-interleukin-17 therapy for linear porokeratosis.

Br J Dermatol

This case report describes a patient with refractory porokeratosis ptychotropica who experienced substantial improvement in symptoms with upadacitinib treatment.

Treatment of Porokeratosis Ptychotropica With Upadacitinib.

Treatment of Porokeratosis Ptychotropica With Upadacitinib

<jats:sec><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and Measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Trial Registrations</jats:title><jats:p>Measure Up 1 trial: ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT03569293">NCT03569293</jats:ext-link>; Measure Up 2 trial: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT03607422">NCT03607422</jats:ext-link>; AD Up trial: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT03568318">NCT03568318</jats:ext-link></jats:p></jats:sec>

Atopic dermatitis.

Lancet

Nat Rev Dis Primers

Prevalence and incidence of atopic dermatitis: a systematic review.

Acta Derm Venereol

The prevalence of atopic dermatitis beyond childhood: a systematic review and meta-analysis of longitudinal studies.

Allergy

Atopic dermatitis in adolescence.

Dermatol Rep

The burden of atopic dermatitis: summary of a report for the National Eczema Association.

Association between hospital-diagnosed atopic dermatitis and psychiatric disorders and medication use in childhood.

A qualitative study on dupilumab’s impact on atopic dermatitis among adolescent and adult patients.

J Drugs Dermatol

Suicide and suicidality in children and adolescents with chronic skin disorders: a systematic review.

Guidelines of care for the management of atopic dermatitis: section 2. management and treatment of atopic dermatitis with topical therapies.

Guidelines of care for the management of atopic dermatitis: section 1. diagnosis and assessment of atopic dermatitis.

Guidelines of care for the management of atopic dermatitis: section 3. management and treatment with phototherapy and systemic agents.

Guidelines for treatment of atopic eczema (atopic dermatitis) part II.

J Eur Acad Dermatol Venereol

Guidelines for treatment of atopic eczema (atopic dermatitis) part I.

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.

Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials.

Efficacy and safety of upadacitinib in patients with moderate to severe atopic dermatitis: analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials.

Upadacitinib plus topical corticosteroids in atopic dermatitis: week 52 AD Up study results.

J Allergy Clin Immunol

Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial.

Safety of upadacitinib in moderate-to-severe atopic dermatitis: an integrated analysis of phase 3 studies.

Eczema herpeticum: clinical and pathophysiological aspects.

Clin Rev Allergy Immunol

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.
To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks.
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.
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.
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.
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.
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.
Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks.

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis

Contact Dermatitis

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Real‐world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient‐Oriented Eczema Measure (POEM), Patient‐Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib‐treated patients. Adverse events were monitored during each visit.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Thirty‐eight patients were included, of which 32 patients had HE. At Week 16, EASI‐75 was achieved by 50.0%. Absolute cutoff score NRS‐pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT &lt;7 by 68.8%, and PGAD rating of at least ‘good’ by 53.1%. HECSI‐75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub‐analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non‐atopic individuals.</jats:p></jats:sec>

publication_history

received

accepted

published

Pfizer

Sanofi

Real-world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited.
To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD.
This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib-treated patients. Adverse events were monitored during each visit.
Thirty-eight patients were included, of which 32 patients had HE. At Week 16, EASI-75 was achieved by 50.0%. Absolute cutoff score NRS-pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT <7 by 68.8%, and PGAD rating of at least 'good' by 53.1%. HECSI-75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub-analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials.
Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non-atopic individuals.

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry.

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the <scp>BioDay</scp> registry

Papers