bluuebunny/crossref_metadata_2025 huggingface dataset:
Brodalumab Versus Ustekinumab in Obese Patients With Moderate-to-Severe Plaque Psoriasis
Authors: Hsu Sylvia , Armstrong April , Green Lawrence , Lebwohl Mark , Jacobson Abby
Published: November 2024

Introduction: Obesity is associated with psoriasis severity and decreased efficacy of psoriasis therapy.1 Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.2 This post hoc analysis evaluated clinical outcomes of treatment with brodalumab in obese versus nonobese participants with moderate-to-severe plaque psoriasis from phase 3 randomized controlled studies (AMAGINE-1/-2/-3).
Methods: Subgroups included in this analysis comprised obese (body mass index [BMI] ≥30 kg/m2) and nonobese participants (BMI <30 kg/m2) who received brodalumab 210 mg every 2 weeks (AMAGINE-1/-2/-3) or ustekinumab (AMAGINE-2/-3) through 52 weeks. Outcomes included psoriasis area and severity index 90% and 100% improvement (PASI 90 and 100) and treatment-emergent adverse events (TEAEs).
Results: AMAGINE-1 included 108 obese and 114 nonobese participants receiving brodalumab.3 At week 12, 59.3% and 27.8% of obese participants receiving brodalumab achieved PASI 90 and 100, respectively. Rates further improved by week 52 (PASI 90: 71.1%; PASI 100: 52.6%). At both time points, nonobese participants achieved higher rates of PASI 90 and 100 compared with obese participants. AMAGINE-2/-3 included 91 obese and 157 nonobese participants receiving brodalumab and 131 obese and 185 nonobese participants receiving ustekinumab.4 For obese participants receiving brodalumab, rates of PASI 90 and 100 were 74.7% and 49.5%, respectively, at week 12; these rates further improved by week 52 (PASI 90: 87.9%; PASI 100: 64.8%) and were higher compared with those of obese participants receiving ustekinumab (PASI 90: 76.3%; PASI 100: 51.9%). Indeed, regardless of BMI, the percentages of PASI 90 and 100 responders were greater with brodalumab compared with ustekinumab. By week 52, PASI responses were similar among nonobese and obese participants in each respective treatment group. Through 52 weeks, TEAEs per 100 patient-years were reported in participants receiving brodalumab (AMAGINE-1, obese: 370.8, nonobese: 388.7; AMAGINE-2/-3, obese: 366.3, nonobese: 404.4) and ustekinumab (AMAGINE-2/-3, obese: 420.6, nonobese: 366.5).
Conclusion: Regardless of BMI, brodalumab demonstrated sustained efficacy in participants with moderate-to-severe plaque psoriasis with no new safety signals.
Evaluation of Changes in Laboratory Parameters from a Phase 2b Trial of Zasocitinib (TAK-279), an Oral, Selective TYK2 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis
Authors: Gooderham Melinda , Bunick Christopher , Kircik Leon H. , Lynde Charles , Skov Lone , Blau Jessamyn , Zhang Wenwen , Uy Jonathan , Winkelman Warren , Thaçi Diamant
Published: November 2024

Background: Zasocitinib (TAK-279) is an oral, allosteric, and highly selective tyrosine kinase 2 inhibitor. In a recent phase 2b trial (NCT04999839), more patients with moderate-to-severe plaque psoriasis treated with zasocitinib 15 and 30 mg once daily achieved 75% improvement in the psoriasis area and severity index at Week 12 (primary endpoint) than those receiving placebo (PBO; p < 0.001). Here we report an assessment of laboratory parameters from this study.
Methods: In this randomized, multicenter, double-blinded, PBO-controlled study, adults with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive oral zasocitinib (2, 5, 15 or 30 mg) or PBO once daily for 12 weeks. The safety analysis set included all patients who received ≥1 dose of the assigned study treatment. Laboratory parameters assessed throughout the trial included creatine kinase (CK), as well as hematologic (neutrophils, lymphocytes, hemoglobin, platelets), hepatic and renal (alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, estimated glomerular filtration rate), and lipid (cholesterol, triglycerides) parameters.
Results: In total, 259 patients were included in the safety analysis set. Longitudinal changes in all laboratory parameters were generally similar in the PBO and zasocitinib groups. Mean values of most laboratory parameters remained within normal ranges during the study. There was no relationship between zasocitinib treatment and cytopenia. Some CK elevations were observed in both the PBO and zasocitinib groups, but most were transient or reversible and of Common Terminology Criteria for Adverse Events Grade 1 or 2 (Grade ≥2 events occurred in 2 [3.8%], 2 [4.0%], 6 [11.5%], 4 [7.5%] and 3 [5.8%] patients, in the PBO, and 2, 5, 15 and 30 mg groups, respectively), and were not associated with rhabdomyolysis. Mean triglyceride values were slightly higher than normal ranges at baseline and Week 12 in all treatment groups, including PBO, and were mainly asymptomatic, mild-to-moderate elevations. These changes were not accompanied by increases in serum cholesterol levels.
Conclusion: Zasocitinib treatment did not result in adverse changes in hematologic, hepatic, renal or lipid parameters that are associated with Janus kinase (JAK) inhibition, suggesting that the mechanism of action of zasocitinib is distinct from that of JAK1/2/3 inhibition. Further phase 3 studies of zasocitinib in psoriasis are ongoing to confirm these observations (NCT06088043; NCT06108544).
Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 4-Year Analysis of the KEEPsAKE 1 and 2 Trials
Authors: Östör Andrew , Glotfelty Lila , Rocco Jonathon , Yue Cuiyong , Merola Joseph F
Published: November 2024

Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~4 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.
Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo for 24 weeks and open-label risankizumab 150 mg thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). All data were reported as observed.
Results: Among patients who achieved ACR20 at week 24 in KEEPsAKE 1 or KEEPsAKE 2, 70.7% and 86.4% maintained ACR20 responses at week 196. Similarly, ACR20 response was maintained to week 196 by 85.7% and 83.3% of week 52 responders in KEEPsAKE 1 and 2, respectively. Similar patterns of maintenance of response were observed for ACR50 and ACR70. Most patients also maintained MDA at week 196 from weeks 24 and 52 (Week 24: KEEPsAKE 1, 86.0%; KEEPsAKE 2, 81.3%; Week 52: KEEPsAKE 1, 81.2%; KEEPsAKE 2, 85.5%). The PASI 90 response was maintained at week 196 from weeks 24 and 52 (Week 24: KEEPsAKE 1, 88.2%; KEEPsAKE 2, 94.9%; Week 52: KEEPsAKE 1, 92.6%; KEEPsAKE 2, 97.1%). Weeks 24 and 52 responders maintained clinically meaningful reductions in pain VAS at week 196 (Week 24: KEEPsAKE 1, 90.2%; KEEPsAKE 2, 88.9%; Week 52: KEEPsAKE 1, 88.3%; KEEPsAKE 2, 90.1%), respectively.
Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 maintained ACR20/50/70, MDA, or PASI90 responses and meaningful pain reduction through week 196.
Long-Term Efficacy and Safety of Risankizumab for csDMARD-IR Patients With Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 1 Trial
Authors: Behrens Frank , Keiserman Mauro , Papp Kim , White Douglas , Crowley Angela , Madihlaba Tshepiso , Iyile Thomas , Carter Kyle , Soliman Ahmed , Ashley Doug , Glotfelty Lily
Published: November 2024

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 from the KEEPsAKE 1 trial.
Materials & Methods: The ongoing KEEPsAKE 1 clinical trial is a global, phase 3, multicenter study to evaluate the efficacy and safety of RZB versus placebo (PBO) in patients with active PsA. Patients are at least 18 years old and demonstrated an inadequate response, intolerance or contraindication to ≥1 conventional synthetic disease modifying antirheumatic drug (csDMARD-IR). Following a 24-week double-blind, PBO-controlled, parallel-group treatment period (period 1), all patients received open-label RZB every 12 weeks thereafter (period 2). Safety assessments were based on monitoring of treatment-emergent adverse events (TEAEs) reported as events per 100 patient-years (PY). Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug.
Results: Overall efficacy results were maintained at week 196 of the KEEPsAKE 1 trial, as compared to previously reported timepoints. At week 196, 39.4% of patients receiving continuous RZB and 38.1% of PBO/RZB patients achieved ACR50; 39.6% of RZB and 35.2% of PBO/RZB patients achieved MDA. In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 65.2% on RZB and 62.9% on PBO/RZB achieved PASI90 at week 196. mNAPSI and PGA-F scores improved from baseline by 14.99 and 1.5 points, respectively, for RZB, and by 14.73 and 1.5 points for PBO/RZB patients. In patients with enthesitis at baseline, 60.1% on RZB and 63.4% on PBO/RZB achieved resolution. For patients with dactylitis at baseline, 72.3% on RZB and 77.6% on PBO/RZB achieved resolution. HAQ-DI (RZB -0.40, PBO/RZB -0.33), SF-36 PCS (RZB 8.98, PBO/RZB 7.21) and FACIT-Fatigue (RZB 7.7, PBO/RZB 5.6) scores maintained improvement from baseline to week 196. The overall rates of TEAEs (121.4 E/100PY), serious TEAEs (7.7 E/100PY) and AEs leading to discontinuation of study drug (1.8 E/100PY) have remained stable and comparable to those reported in period 1.
Conclusion: The 196-week results of the ongoing KEEPsAKE 1 trial demonstrate the durable efficacy of RZB 150 mg in treating the different clinical manifestations and improving health-related quality of life in csDMARD-IR patients with PsA. RZB continued to be well-tolerated, with no new safety signals.
Long-Term Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 196-Week Results From the KEEPsAKE 2 Trial
Authors: Östör Andrew , Van den Bosch Filip , Papp Kim , Asnal Cecilia , Blanco Ricardo , Aelion Jacob , Biljan Ana , Rocco Jonathon , Liu Fang , Soliman Ahmed , Ashley Doug , Glotfelty Lila , Kivitz Alan
Published: November 2024

Introduction & Objectives: Here, we report the long-term efficacy and safety of risankizumab (RZB) in patients with active psoriatic arthritis (PsA) through week 196 of the KEEPsAKE 2 trial. 
Materials & Methods: Adult patients with previous inadequate response or intolerance to 1 or 2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) were randomized in a 1:1 ratio to subcutaneous RZB 150mg or matched placebo for a 24-week double-blind placebo controlled period. Starting at week 28, patients received open-label RZB every 12 weeks thereafter. Efficacy and safety analyses were conducted in all randomized patients who received ≥1 dose of the study drug. Statistical approaches included non-responder imputation incorporating multiple imputation (NRI-MI) for binary endpoints, and mixed-effect model for repeated measures (MMRM) for categorical endpoints at week 196. Safety assessments based on treatment emergent adverse events (TEAEs) are summarized using exposure-adjusted event rates (EAERs, events/100 patient-years [E/100PYs]).
Results: 51.3% of patients on RZB 150mg (N=224) achieved the primary endpoint of ACR20 at week 24 compared to 26.5% on placebo (N=219). Patients on open-label RZB maintained similar efficacy results at week 196 as those reported previously at weeks 24, 52, 100, and 148. At week 196, 54.5% patients receiving continuous RZB and 50.2% patients on PBO/RZB achieved ACR20; 35.3% on RZB and 37.0% on PBO/RZB achieved ACR50; 35.3% on RZB and 37.4% on PBO/RZB achieved minimal disease activity (MDA). In patients with psoriasis severity of ≥ 3% of body surface area (BSA) at baseline, 66.7% on RZB and 56.3% on PBO/RZB achieved PASI90 at week 196. In patients with enthesitis at baseline, 49.0% on RZB and 50.0% on PBO/RZB achieved resolution. In patients with dactylitis at baseline, 75.0% on RZB and 59.6% on PBO/RZB achieved resolution. Among patients with HAQ-DI scores of at least 0.35 at baseline, 36.7% on RZB and 40.6% on PBO/RZB achieved improvements of at least 0.35 at week 196. The overall rates of TEAEs (170.7 E/100PYs), serious TEAEs (9.8 E/100PYs) and AEs leading to discontinuation of study drug (1.4 E/100PYs) remained stable and consistent with rates reported previously at week 24 for the placebo-controlled period, and weeks 52, 100, and 148.
Conclusion: The 196-week results from KEEPsAKE 2 demonstrate that long-term treatment with RZB shows durable efficacy in Bio-IR and/or csDMARD-IR patients with PsA, with no new safety findings.
Utilization and Duration of Systemic Corticosteroid Exposure in Atopic Dermatitis Patients After the Introduction of Advanced Therapies: A Population-Based Study From the United States
Authors: Bunick Christopher , Vleugels Ruth Ann , Lebwohl Mark , Grada Ayman , Yue Emma Xiaomeng , Wegrzyn Lani , D'Andrea Elvira
Published: November 2024

Introduction: Clinical guidelines discourage routine use of systemic corticosteroids (SCS) for the management of atopic dermatitis (AD). However, adherence to these guidelines remain unclear. This is particularly relevant given the availability of advanced systemic treatments, including biologics and JAK inhibitors, for AD. We investigated the utilization and duration of SCS exposure among AD patients after the introduction of advanced therapies.
Methods: Using the U.S. Optum CDM database from 03/2017 to 03/2024, we defined a cohort of AD patients ≥ 12 years old who initiated oral or intramuscular SCS. To increase the likelihood that the SCS treatment was related to AD, we limited the cohort to recently diagnosed AD patients (within the preceding 6 months) without recent diagnoses of immuno-mediated diseases, asthma, osteoarthritis, dorsalgia, gout, bursitis, tendonitis, carpal tunnel, or a history of malignancies, organ transplant or HIV/AIDS. Continuous health insurance enrollment was required for at least 1 year before and after initiating SCS. We followed patients until the end of available data, health insurance discontinuation, or death to determine exposure duration. Exposure time was categorized as short-term (<30 days), medium-term (30-90 days), or long-term (>90 days) based on data observation and clinical experience. Categorical and continuous variables were presented as numbers and percentages or mean and standard deviation values, respectively.
Results: During the study period, 29,994 patients aged 12 years or older with a recent AD diagnosis initiated SCS treatment, representing 20% of eligible AD patients. Most SCS initiators were prescribed oral SCS (80%). Of all users, 67.7% (20,293) received SCS for a short-term period, while 8.5% (2,535) for a medium-term duration, and 23.9% (7,166) for a long-term period. Overall, the average age was 50 (±22) years old. Short-term SCS users had a higher percentage of patients under 30 years old (27%) compared to medium-term (19.7%) and long-term users (16.1%). Patients in all three groups were mostly female (58-60%). At baseline, long-term users received slightly higher prescriptions of biologics (3.3% vs 3.1% and 2.5%) and immunosuppressants (2.6% vs 1.9% and 1.2%) compared to medium-term and short-term users and had higher usage of non-steroidal anti-inflammatory drugs (19.2% vs 15.2% and 13.5%). Dermatologist visits were similar among the three groups, with medium-term users having the highest proportion of encounters (33.9%).
Conclusion: Despite clinical guidelines advising against the use of SCS for AD, they remain widely prescribed, and a relevant proportion of patients are exposed to SCS for extended durations (over 90 days).
Real-World Effectiveness of Upadacitinib in Moderate‑to‑Severe Atopic Dermatitis (AD): Results From Longitudinal Analyses of the CorEvitas AD Registry
Authors: Silverberg Jonathan I. , Gooderham Melinda , Bunick Christopher G. , Calimlim Brian , Grada Ayman , Muñoz Maldonado Yolanda , Li Alvin , Fergestrom Nicole , Simpson Eric
Published: November 2024

Introduction: Clinical trials demonstrated that upadacitinib is efficacious in treating atopic dermatitis (AD).  Its real-world effectiveness is less understood.  In this study, we investigated the longitudinal real-world outcomes of upadacitinib-treated adults in the CorEvitas AD Registry.
Methods: The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD in the United States and Canada. We evaluated participants enrolled through April 30, 2024 with data available prior to upadacitinib exposure (baseline) and at the six-month follow-up visit, and were receiving upadacitinib at the follow-up visit.  Outcomes evaluated include the achievement of: Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) of “clear” or “almost clear” among participants rated “mild” or worse at baseline (vIGA-AD 0/1); Eczema Area and Severity Index improvement of ≥75%/≥90%/100% from baseline (EASI 75/90/100); Peak Pruritus Numeric Rating Scale (PP-NRS) improvement ≥4 among participants with a score ≥4 at baseline (∆PP-NRS≥4); PP-NRS score of 0 or 1 among participants with a score >1 at baseline (PP-NRS 0/1); Dermatology Life Quality Index (DLQI) score improvement ≥4 among participants with a score ≥4 at baseline (∆DLQI≥4); and DLQI score of 0 or 1 among participants with a score >1 at baseline (DLQI 0/1). Simultaneous achievement of both EASI 90 & PP-NRS 0/1 was also assessed. Data were analyzed as observed with no imputation. Safety events were not assessed in this analysis.
Results: The longitudinal analysis included 192 participants (mean age 46.2 years; 57.8% female; 69.8% White; 43.8% prior exposure to dupilumab or tralokinumab; 64.4% receiving 15 mg dose at follow-up visit; mean upadacitinib treatment duration of 6.0 months).  More than half achieved clear/almost clear skin (66.1% vIGA-AD 0/1), EASI 75 (69.3%), and EASI 90 (59.2%); 45.3% achieved complete skin clearance (EASI 100).  More than 40% reported little-to-no itch (44.4% PP-NRS 0/1) and no impact of AD on quality of life (43.3% DLQI 0/1), and more than half reported meaningful improvements in itch (58.6% ∆PP-NRS≥4) and quality of life (76.0% ∆DLQI≥4).  Simultaneous attainment of both EASI 90 & PP-NRS 0/1 was achieved in 46.6% of participants at 6 months.
Conclusions: In the real-world setting, the majority of adults treated and remained on upadacitinib achieved clinically meaningful outcomes in skin lesions, itch, and quality of life, with many achieving complete skin clearance, little-to-no itch, and experiencing no impact of AD on their quality of life. These findings underscore upadacitinib's potential to offer multidimensional relief to patients with AD in everyday clinical practice.
Optimized Second-Generation IL-4Rα Inhibition: Structural and Molecular Dynamics Properties of Rademikibart Fab-IL-4Rα Complex
Authors: Shi Yuanjun , Ho Minh , Li Haote , Collazo Raul , Bunick Christopher
Published: November 2024

Introduction: Global Burden of Disease studies showed atopic dermatitis (AD) and asthma are the top two immune-mediated inflammatory diseases at younger age [1]. Dupilumab was the initial first-generation interleukin-4 receptor alpha (IL-4Rα) inhibitor for treating both type I and type II IL-4Rα-dependent inflammatory disorders. Following recent clinical trials, rademikibart (previously, CBP-201) emerges as an optimized next-generation human monoclonal antibody with higher binding affinity to IL-4Rα compared to dupilumab [2]. It demonstrated better effect in inhibiting STAT6 intracellular signaling in vitro and provided similar potency inhibiting both IL-4 induced TARC release and IL-4 induced B cell activation [2].
Materials & Methods: X-ray crystallography was used to determine the atomic resolution 3D structure of rademikibart fragment antigen binding (Fab) bound to IL-4Rα. This structure was analyzed and compared computationally with the 2.82 Å resolution crystal structure of dupilumab Fab bound to IL-4Rα (Protein Data Bank Code 6WGL). Molecular dynamics studies on rademikibart and dupilumab bound to IL-4Rα examined the stability of the complexes and effects of amino acid mutations on complex formation.
Results: The x-ray crystal structure of rademikibart Fab bound to IL-4Rα was determined at 2.71Å and compared to the complex of dupilumab Fab and IL-4Rα. The rotation angle between dupilumab and rademikibart bound to IL- 4Rα is 59.17°. This rotation enables the epitope of rademikibart, but not dupilumab, on IL-4Rα to overlap more closely with the conserved binding interface utilized by IL-4 and IL-13 cytokines. Molecular dynamics simulations of rademikibart Fab and dupilumab Fab complexed with IL-4Rα showed the third interface loop (residues 148 to 152 in domain 2) of IL-4Rα interacts directly with rademikibart, which is absent in dupilumab/IL- 4Rα complex. This finding is confirmed by analysis of the hydrogen bond interactions at the interface between the antibodies and IL-4Rα, demonstrating superior binding energy for rademikibart. Through single amino acid mutation analysis on rademikibart, we identified residue Y50 on rademikibart as the key residue interacting with IL- 4Rα’s third interface loop.
Conclusion: Our data provide a molecular and structural rationale for the enhanced IL-4Rα inhibition by rademikibart over dupilumab, confirming rademikibart as an optimized second-generation IL-4Rα inhibitor.
Efficacy and Safety of Ruxolitinib Cream by Anatomic Region in Children Aged 2 to 11 Years With Atopic Dermatitis: Results From TRuE-AD3
Authors: Siri Dareen , Paller Amy , Armstrong April , Stein Gold Linda , Kallender Howard , Sturm Daniel , Ren Haobo , Eichenfield Lawrence
Published: November 2024

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Ruxolitinib (Janus kinase [JAK]1/JAK2 inhibitor) cream has demonstrated efficacy and safety in patients aged ≥2 years with AD. In adolescents (aged ≥12 y) and adults with AD, application of ruxolitinib cream resulted in significant improvements across all anatomic regions vs vehicle. The objective of this analysis was to evaluate the efficacy and safety of ruxolitinib cream by anatomic region in the randomized, double-blind, phase 3 TRuE-AD3 study (NCT04921969). Children aged 2–11 years with AD for ≥3 months and an Investigator’s Global Assessment score of 2/3 were randomized 2:2:1 to apply 0.75% or 1.5% ruxolitinib cream twice daily (BID) or vehicle BID for 8 weeks. Efficacy was evaluated using the Eczema Area and Severity Index (EASI) subscores for head/neck, trunk, upper limbs, and lower limbs. Of 330 patients in TRuE-AD3, the mean (SD) age was 6.5 (2.9) years, and 179 patients (54.2%) were female; the mean (SD) EASI score was 8.6 (5.4). Improvements in EASI score were demonstrated with 0.75% and 1.5% ruxolitinib cream vs vehicle at first observation (Week 2), with statistically significant differences (at 0.05 alpha level and all P values below are nominal) at Week 8 in the head and neck (−0.63 [P=0.0108] and −0.70 [P=0.0011] vs −0.41), trunk (−0.98 [P=0.0310] and −1.18 [P=0.0003] vs −0.70), upper limbs (−1.81 [P<0.0001] and −2.06 [P<0.0001] vs −1.18), and lower limbs (−2.91 [P<0.0001] and −3.23 [P<0.0001] vs −1.43). Improvements in induration/papulation/edema, erythema, excoriation, and lichenification were observed for both strengths of ruxolitinib cream vs vehicle in all regions at Week 2, with statistical significance (at 0.05 alpha level) in nearly all AD signs and regions at Week 8. Ruxolitinib cream was well tolerated in both treatment groups (n=264), with 4.5% of patients experiencing application site reactions, which was similar to the frequency of application site reactions (4.3%) among patients with head/neck involvement (n=161) . In conclusion, ruxolitinib cream demonstrated significant improvements in AD vs vehicle in children with AD across anatomic regions, including on the head/neck, and was well tolerated. (Funding, Incyte Corporation)
Patient and Parent/Caregiver Satisfaction with Efficacy and Cosmetic Elegance of Tapinarof Cream 1% Once Daily in a Long-term Extension Trial in Adults and Children Down to Age 2 Years with Atopic Dermatitis
Authors: Hebert Adelaide A. , Del Rosso James , Johnson Sandra Marchese , Green Lawrence J. , Serrao Sarah , Brown Philip M. , Rubenstein David S. , Tallman Anna
Published: November 2024

Introduction: Patients with atopic dermatitis (AD) report low satisfaction with currently available topical therapies. Satisfaction and patient preference are closely linked to treatment adherence, and understanding preferences may contribute to improving the quality of AD care and adherence. In the pivotal 8-week, phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated superior efficacy versus vehicle and was well tolerated in adults and children down to age 2 years with AD. We report Patient Satisfaction Questionnaire© (PSQ) results from ADORING 3, a 48-week, open-label extension trial.
Methods: In ADORING 3, eligible patients from ADORING 1 and 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild AD, or moderate or severe AD, that did not meet inclusion criteria for ADORING 1 or 2, were followed for up to 48 weeks. The PSQ was completed at Week 48 or at early termination visit and assessed patient or parent/caregiver satisfaction with tapinarof efficacy, cosmetic elegance (look and feel of tapinarof cream), application ease, impact on daily life, and preference for tapinarof versus prior AD therapies. Patients aged ≥16 years self-completed the PSQ; parents/caregivers completed for children aged 2 to 15 years.
Results: 505 patients or parents/caregivers completed the questionnaire. Respondents consistently reported high rates of satisfaction across all parameters. Most patients or parents/caregivers strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (91.5%), quick absorption (89.5%), application ease (97.6%), impact on daily life (94.3%), efficacy (92.3%), and confidence in tapinarof (92.7%). For patients or parents/caregivers who reported prior use of other topical therapies to treat AD, most strongly agreed or agreed that tapinarof was more effective (86.3%), easier to use (68.6%), and that they preferred tapinarof to prior topicals (88.0%). Compared with systemic drugs used previously for AD, most strongly agreed or agreed that tapinarof was more effective (84.6%), easier to use (77.6%), and that they preferred tapinarof to prior systemic drugs (85.9%).
Conclusion: Patient or parent/caregiver satisfaction data from ADORING 3 showed a consistent and highly positive perception of long-term use of tapinarof cream across all parameters, including satisfaction with tapinarof efficacy, cosmetic elegance, application ease, impact on daily life, and preference for tapinarof compared with prior AD therapies. Satisfaction with tapinarof is likely to contribute to long-term adherence and improved outcomes for patients with AD.
Skin Clearance, Treatment Response Off-therapy, and Safety of Tapinarof Cream 1% Once Daily: Results from ADORING 3, a 48-week Phase 3 Trial in Adults and Children Down to 2 Years of Age with Atopic Dermatitis
Authors: Bissonnette Robert , Stein Gold Linda , Kircik Leon , Simpson Eric , Eichenfield Lawrence F. , Browning John , Hebert Adelaide A. , Alexis Andrew F. , Soong Weily , Piscitelli Stephen C. , Tallman Anna , Rubenstein David S. , Brown Philip M. , Silverberg Jonathan I.
Published: November 2024

Introduction: In the ADORING 1 and 2 phase 3 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis (AD). We present efficacy, safety, and tolerability outcomes from ADORING 3.
Methods: Eligible patients from ADORING 1, ADORING 2, from a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients with mild, or moderate or severe AD, that did not meet eligibility criteria for ADORING 1 or 2, received tapinarof cream 1% QD for up to 48 weeks. Efficacy endpoints included achievement of complete disease clearance (Validated Investigator Global Assessment for Atopic Dermatitis™ [vIGA-AD™] score=0 [clear]), and clear or almost clear skin (vIGA-AD™=0 or 1). Safety and tolerability were assessed. Patients entering with vIGA-AD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0 [clear]). Those entering with or achieving complete clearance discontinued tapinarof and were assessed for maintenance of clear or almost clear skin off-treatment (duration of treatment-free interval). Patients whose AD returned to mild (vIGA-AD™≥2) were re-treated until complete clearance was achieved.
Results: 728 patients enrolled; 83.0% were pediatric (2–17 years). Overall, 51.9% (378/728) achieved complete disease clearance, and 81.6% achieved clear or almost clear skin at least once in the trial. Mean duration of first treatment-free interval was 79.8 consecutive days (standard deviation: 81.4 days). No tachyphylaxis on either continuous or intermittent therapy was observed for up to 48 weeks. Most frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%). Follicular events and contact dermatitis were mostly mild or moderate and associated with low discontinuations (1.0% and 0.4%, respectively). Tapinarof was well tolerated locally, even when applied on sensitive skin.
Conclusions: Tapinarof cream monotherapy demonstrated a high rate of complete disease clearance in patients down to age 2 years with AD. After discontinuing tapinarof, patients maintained clear or almost clear skin for 79.8 consecutive days. Tapinarof was well tolerated over 48 weeks.
Why Do Optimal Targets for Itch and Skin Clearance Matter in Atopic Dermatitis Treatment? Insights from TARGET-DERM AD Registry
Authors: Silverberg Jonathan , Bunick Christopher , Calimlim Brian , Grada Ayman , Knapp Keith , Munoz Breda , Crawford Julie , Obi Chibuzo , Paller Amy
Published: November 2024

Introduction/Background: Atopic dermatitis (AD) patients undergoing treatment may only experience partial improvement in itch and skin lesions, often leading to suboptimal outcomes. The Aiming High in Eczema/Atopic Dermatitis (AHEAD) treat-to-target recommendations emphasize the importance of achieving optimal treatment targets, such as complete or near-complete itch relief and skin clearance. However, there is limited evidence on the impact of achieving these higher efficacy targets on patient-reported outcomes and quality of life in AD.
Objectives: To evaluate the independent and combined effects of achieving optimal treatment targets for itch and skin clearance on patient-reported outcomes (PROs) in AD, based on the AHEAD treat-to-target recommendations.
Method: A cross-sectional analysis was conducted on adult participants in TARGET-DERM AD, a longitudinal study with over 4,000 participants across 52 U.S. and Canadian clinical-practice sites (2019-2024). Itch severity was measured using the PROMIS Itch-Severity question (NRS-Itch, 0–10 scale), with scores of 0/1 indicating no or minimal itch. Skin severity was assessed using the validated Investigator Global Assessment (vIGA-AD), where 0/1 represents clear or almost clear skin. Associations between itch and skin severity with optimal patient outcomes including POEM 0–2 (clear/almost-clear disease), DLQI 0/1 (minimal/no impact on quality of life), NRS-Sleep 0/1, and NRS-Pain 0/1 were evaluated. Logistic regression models examined the main and interaction effects of itch and skin severity.
Results: Among 1,920 patients (58.6% female; 54.5% Non-Hispanic White; 93.8% US; mean age 45 years), optimal DLQI, POEM, NRS-Sleep, and NRS-Pain occurred most frequently among those achieving the optimal treatment targets for itch (WI-NRS 0/1; 52.1%, 53.7%, 57.3%, and 83.1%, respectively) and skin clearance (vIGA-AD 0/1; 44.7%, 44.3%, 44.7%, and 74.3%, respectively).  Compared to partial improvement, the adjusted odds ratios (aOR) of optimal PROs were greatest for participants with complete or near-complete resolution of both itch and skin lesions (DLQI 0/1: 20.0; POEM 0-2: 41.7; Sleep-NRS: 16.1; Pain-NRS: 6.0).
Conclusions: Achieving optimal treatment targets for both itch and skin lesions markedly enhances patient-reported outcomes in AD.  The results of this real-world study support treat-to-optimal targets to assess therapeutic effectiveness and optimize patient outcomes.
Persistent Inadequate Disease Control and Therapeutic Inertia in Moderate-to-Severe Atopic Dermatitis: A 12-month Longitudinal Analysis of Real-world Outcomes from the TARGET-DERM AD registry
Authors: Eichenfield Lawrence , Grada Ayman , Knapp Keith , Munoz Breda , Crawford Julie , Silverberg Jonathan
Published: November 2024

Background: Therapeutic inertia refers to the delay or failure in treatment escalation in patients not achieving adequate disease control; it is a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored.
Objectives: This study evaluates the occurrence of therapeutic inertia and the proportion of patients with moderate-to-severe AD who continue to show inadequate response after receiving systemic therapies for a duration from 3 to 12 months
Methods: We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up.  We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting treatment targets based on expert consensus.  An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution).
Results: Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P<0.01).  At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend.
Conclusions: The study reveals that a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.
Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials
Authors: Vleugals Ruth Ann , Mostaghimi Arash , Sinclair Rodney , Piraccini Bianca Maria , Sontag Angelina , Somani Najwa , Denning Karen , Srivastava Ayush , King Brett
Published: November 2024

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment.
Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications.
Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia.
Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.
Patient Profile and Treatment Characteristics of Early Ritlecitinib Initiators in the US
Authors: Kurosky Samantha K. , Takiya Liza , Hanson Kent , Bell Griffith , Lee Yi-Chien , Gauthier Genevieve
Published: November 2024

Introduction: Alopecia Areata (AA) is an autoimmune disease characterized by unpredictable, non-scarring hair loss. In the ALLEGRO phase 2b/3 randomized, placebo-controlled clinical trial, ritlecitinib 50mg demonstrated a significantly greater proportion of patients achieving 80% or more scalp hair coverage at 24 weeks compared to placebo. In June 2023, the FDA approved ritlecitinib (50mg) for treatment of severe AA in adults and adolescents 12 years and older. This study aims to address how ritlecitinib is being integrated into real-world practice by assessing the characteristics of patients prescribed ritlecitinib within the first three months following approval.
Methods: This was a retrospective observational study analyzing data from the Komodo Healthcare Map (TM) dataset (Jan 2016-Sept 2023). Komodo Healthcare Map is comprised of open and closed claims for more than 330M lives in the US. The sample included patients aged ≥12 years with ≥1 prescription for ritlecitinib on or after June 23, 2023 (first prescription date defined the index date), ≥1 diagnoses of AA on or before the index date, and ≥12 months of continuous enrollment/eligibility proxy prior to study entry. Clinical characteristics, comorbidities, and AA treatment history were assessed over the 12-month pre-index period. All variables were analyzed descriptively and stratified by age (adolescent: 12-17, adult: ≥18).
Results: Among the 150 patients included, 72% were prescribed ritlecitinib by a dermatologist. Over half were female, 52% were adolescents, and 78% were commercially insured. Approximately 30% of patients had alopecia totalis/alopecia universalis (AT/AU); 11% had ≥1 other autoimmune disorder, 23% had ≥1 atopic disorder, and 21% had ≥1 mental/emotional disorders. In the 12 months prior to receiving ritlecitinib, 34% of adolescents received no AA treatments, 30% received systemic immunomodulators (19% Janus kinase inhibitors [JAKi], 13% other systemic immunomodulators), and 20% received topical corticosteroids. Among adults, 24% had no evidence of prior AA treatments, 35% received injectable corticosteroids, and 35% received systemic immunomodulators (21% baricitinib, 13% other JAKi, and 7% other systemic immunomodulators) during the pre-index period. Of those who had received a prior treatment, the mean time between the last days’ supply of the prior therapy and the start of ritlecitinib was 51 days.
Conclusion: In the first 3 months following the US approval, ritlecitinib was prescribed to a broad range of patients; including adolescent and adults; those with and without prior treatments; and those with and without various comorbidities. This suggests that ritlecitinib may provide new opportunities to (re)engage in AA-directed care.
Funding: this study was funded by Pfizer Inc.
Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA
Authors: Mesinkovska Natasha , Richter Sven , Bristow Claire , Soliman Ahmed , Crawford Julie , Knapp Keith , Munoz Breda , Wine Lee Lara , Chapman Michael , Paller Amy , Ungar Benjamin , Hordinsky Maria
Published: November 2024

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities.
Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups.
Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged <12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients).
42.1% of patients with comorbid vitiligo had severe AA disease (SALT>50) and 27.8% patients without comorbid vitiligo had SALT>50. 28.6% of those with comorbid AD had SALT>50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT>50, all p>0.2.
42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p>.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p>0.5.
Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.
Generic vs. Disease-Specific Patient Reported Outcome (PRO) Instruments for Assessing HRQoL Burden Among Patients Diagnosed with Alopecia Areata: Evidence from TARGET-DERM AA
Authors: Ungar Benjamin , Soliman Ahmed , Bristow Claire , Richter Sven , Munoz Breda , Crawford Julie , Knapp Keith , Mesinkovska Natasha
Published: November 2024

Introduction Alopecia areata (AA) is a chronic, autoimmune disease characterized by patchy hair loss. Compared to other disease areas, recent work has signaled a potential shortcoming, that generic quality of life (QOL) questionnaires are not sufficiently sensitive to the impact of AA disease severity. This cross-sectional analysis investigates the Short-Form 36, the dermatology life quality index (DLQI), and the Alopecia Areata Patient Priority Outcomes (AAPPO) for similar shortcomings.
Methods Patients of all ages enrolled from December 2021 to June 2024 in TARGET-DERM AA (data collection on-going) in the United States and Canada were grouped by Severity of Alopecia Tool (SALT) score (1-20, 21-49, or 50-100). At enrollment, patients completed the AAPPO and DLQI questionnaire as well as the RAND MOS Short-Form 36. The SF-36 has 8 subdomain scores (vitality, physical function, bodily pain, general health, physical role function, emotional role function, social role function, mental health) along with the physical component summaries (PCS), mental component summaries (MCS), and the SF-6D utility index score. The Kruskal-Wallis test compared differences in mean scores across SALT subgroups defined by severity.
Results Of the 141 AA patients, 61.7% were female; 95.0% adults, and 67.4% Non-Hispanic White.
When comparing the SALT 1-20 and the >50 subgroups, significant differences in SF-36 derived mean scores were only observed in the PCS and the physical function score (p<0.05). None of the other scores (MCS, SF-6D, or other SF-36 subdomains) showed any differences. Mean DLQI scores were similar across subgroups (p>.05)
Notably, the hair loss and activity limitation domains of the AAPPO demonstrated significant differences between the patient subgroups (p<.0001 and p<.05, respectively)
Discussion In this real-world cohort, generic QoL instruments, namely the SF-36 and DLQI, did not capture differences in the underlying health-related QoL burden of AA patients with different AA severity. Such differences were clear when HRQoL was measured for AA patients with mild hair loss AAPPO.