J Clin Aesthet Dermatol. 2025;18(1–2 Suppl 1):S36–S52.
Acne
Early acne improvements with fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel: What to expect in the first 4 weeks of treatment
Presenters: Julie C. Harper,1 Leon H. Kircik,2 Michael Gold,3 Adelaide A. Hebert,4 Jeffrey L. Sugarman,5 Lawrence Green,6 Linda Stein Gold,7 Hilary Baldwin,8 James Q. Del Rosso,9 Eric Guenin,10
Affiliations: 1Dermatology & Skin Care Center of Birmingham, Birmingham, AL; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Tennessee Clinical Research Center, Nashville, TN; 4UTHealth McGovern Medical School, Houston; Houston, TX; 5University of California, San Francisco, CA; 6George Washington University School of Medicine, Washington, DC; 7Henry Ford Hospital, Detroit, MI; 8The Acne Treatment and Research Center, Brooklyn, NY; 9JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 10Ortho Dermatologics*,Bridgewater, NJ *Ortho Dermatologics is a division of Bausch Health US, LLC
Introduction: Treatments with fast and substantial acne clearance are highly desirable. While a three-pronged approach can increase treatment efficacy versus monotherapy or dual-combination therapy, it is unknown if triple-combination provides more rapid improvement. CAB gel—clindamycin phosphate (clin) 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1%—is the first fixed-dose, triple-combination acne topical. Since rapid/substantial acne improvements and fewer side effects can increase adherence, the efficacy and safety of CAB in the first four weeks of treatment was evaluated.
Methods: In a Phase 2 (N=741; NCT03170388) and two Phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies, participants aged nine years or older with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel; the Phase 2 study included three additional dyad arms: BPO/adapalene; clin/BPO; and clin/adapalene. Efficacy assessments included least-squares mean percent change from baseline in inflammatory and noninflammatory lesions. Cutaneous safety/tolerability assessments were graded from 0=none to 3=severe. Post-hoc analyses included percentages of participants with one-third and one-half acne lesion reductions.
Results: At Week 4, CAB led to approximately 55 percent reductions from baseline in inflammatory acne lesions in the ph2 and pooled ph3 studies, significantly greater than vehicle (~40%) and its three dyads (ph2 range: 44.2-47.6%; p<0.05, all). The percentages of participants with one-third and one-half reductions of inflammatory lesions were significantly greater with CAB than vehicle and dyads (p<0.05, all). Similar trends were observed for noninflammatory lesions, though reductions were less pronounced. As expected for retinoids, transient increases from baseline to Week 2 in scaling, erythema, itching, burning, and stinging were observed for CAB, BPO/adapalene, and clin/adapalene, with mean scores ≤0.6 (1=mild); no trends in dyspigmentation were observed. Mean scores for all cutaneous assessments were highest for BPO/adapalene, indicating that adding a third product in the fixed-dose CAB gel formulation did not worsen tolerability.
Conclusion: Acne lesion reductions were significantly greater with clin 1.2%/adapalene 0.15%/BPO 3.1% gel versus its dyads and vehicle gel as early as Week 4. More rapid efficacy with this first fixed-dose triple-combination acne product—coupled with its optimized formulation, once-daily dosing, and tolerability—might positively impact treatment adherence.
Funding/financial disclosures: Funding was provided by Ortho Dermatologics.
Efficacy and safety of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel in hispanic participants with moderate-to-severe acne
Presenters: Valerie D. Callender,1,2 Hilary Baldwin,3,4 Linda Stein Gold,5 Fran E. Cook-Bolden, MD,6,7 Andrew F. Alexis,7
Affiliations: 1Callender Dermatology and Cosmetic Center, Glenn Dale, MD; 2Howard University College of Medicine, Washington, DC; 3The Acne Treatment and Research Center, Brooklyn, NY; 4Robert Wood Johnson University Hospital, New Brunswick, NJ; 5Henry Ford Hospital, Detroit, MI; 6Fran E. Cook-Bolden, MD, PLLC, New York, NY; 7Weill Cornell Medicine, New York, NY
Introduction: Acne vulgaris is a common dermatologic condition and a leading dermatologic diagnosis in Black and Hispanic patients. Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for the treatment of acne. In three published clinical studies of participants with moderate-to-severe acne, CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety/tolerability. The objective of these analyses was to determine the efficacy, safety, and tolerability of CAB in Hispanic participants of these studies.
Methods: In one Phase 2 (NCT03170388) and two Phase 3 (NCT04214652, NCT04214639) randomized, double-blind, 12-week studies, participants aged nine years or older with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Endpoints included percentage of participants achieving treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score [EGSS] and clear/almost clear skin) and least-squares mean percent change from baseline in inflammatory/noninflammatory lesion counts at Week 12. Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also assessed. Pooled data across all three studies were analyzed for participants who self-identified as Hispanic/Latino (herein referred to as Hispanic; n=90 CAB; n=57 vehicle gel).
Results: At Week 12, over half of Hispanic participants achieved treatment success with CAB versus less than one-quarter with vehicle gel (56.2% vs. 18.4%; p<0.001). CAB treatment provided more than 75-percent reductions in inflammatory/noninflammatory lesion counts at Week 12 vs 56.4 percent and 45.0 percent, respectively, with vehicle (p<0.001, both). TEAE rates with CAB in the Hispanic population were similar to those in the overall study populations (27% vs. 24.6–36.2%). Most TEAEs were of mild-to-moderate severity, and discontinuations due to AEs were low (<4%). Mean cutaneous safety and tolerability scores (0=none to 3=severe) with CAB at all visits were less than one (mild), similar to the overall study populations. Hyperpigmentation scores decreased from baseline (0.6) to Week 12 (0.3) following CAB treatment.
Conclusion: In Hispanic participants with moderate-to-severe acne treated with CAB, over half achieved treatment success and acne lesion reductions were reduced by more than 75 percent by Week 12, without any additional safety signals. These results, combined with those of previous post-hoc analyses in Black study participants, demonstrate that CAB is an efficacious, safe, and tolerable acne treatment for patients of different racial and ethnic groups.
Funding/financial disclosures: Funding was provided by Ortho Dermatologics.
Impact of age on efficacy and safety of fixed-dose clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel in participants with moderate-to severe acne
Presenters: Leon H. Kircik,1–3 Julie C. Harper,4 Hilary Baldwin,5,6 Lawrence F. Eichenfield,7,8 Emil A Tanghetti,9 Emmy Graber,10,11 Heather C Woolery-Lloyd,12 Zoe D. Draelos,13 Eric Guenin,14
Affiliations: 1Icahn School of Medicine at Mount Sinai, New York, NY; 2Indiana University School of Medicine, Indianapolis, IN; 3Physicians Skin Care, PLLC, DermResearch, PLLC, and Skin Sciences, PLLC, Louisville, KY; 4Dermatology & Skin Care Center of Birmingham, Birmingham, AL; 5The Acne Treatment and Research Center, Brooklyn, NY; 6Robert Wood Johnson University Hospital, New Brunswick, NJ; 7University of California, San Diego School of Medicine, La Jolla, CA; 8Rady Children’s Hospital, San Diego, CA; 9Center for Dermatology and Laser Surgery, Sacramento, CA; 10The Dermatology Institute of Boston, Boston, MA; 11Northeastern University, Boston, MA; 12University of Miami Miller School of Medicine, Miami, FL; 13Dermatology Consulting Services, PLLC, High Point, NC; 14Ortho Dermatologics*, Bridgewater, NJ *Ortho Dermatologics is a division of Bausch Health US, LLC.
Introduction: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the first fixed-dose, triple-combination formulation approved for acne treatment. CAB gel demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability in three clinical studies of participants with moderate-to-severe acne. As acne pathogenesis/treatment outcomes can vary with age, these post-hoc analyses were performed to evaluate CAB efficacy and safety in pediatric and adolescent participants (aged 9–24 years) versus adult participants (≥25 years). This age cutoff was chosen as age 25 years is often used to define “adult acne,” and acne in patients aged 18 to 24 years is more similar to adolescents than adults.
Methods: In one Phase 2 (NCT03170388) and two Phase 3 (NCT04214652, NCT04214639) studies, participants with moderate-to-severe acne aged at least nine years were randomized to once-daily CAB or vehicle gel. Endpoints included percentage of participants achieving treatment success (defined as ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and clear/almost clear skin) and least-squares mean percent change from baseline in inflammatory/noninflammatory lesion counts at Week 12. Treatment-emergent adverse events (TEAEs) were also evaluated. Data pooled across the three studies were analyzed for participants aged 9 to 24 years (CAB: n=297; vehicle: n=218) and at least 25 years (n=91; n=51).
Results: Approximately half of CAB-treated participants in both age groups achieved treatment success (9–24 years: 50.6%; ≥25: 49.0%) versus less than one-fourth with vehicle (15.7% and 20.6%; p<0.01, both) at Week 12. In both age groups, CAB treatment resulted in more than 70-percent reductions from baseline in inflammatory and noninflammatory lesions versus 45–62% with vehicle (p≤0.001, all). There were no significant differences between CAB-treated participants in the two age groups across efficacy endpoints (p=0.68–0.97). The majority of TEAEs with CAB treatment were of mild-to-moderate severity, and there were no age-related trends in safety or tolerability.
Conclusion: CAB fixed-dose, triple-combination gel was efficacious and well tolerated in participants with moderate-to-severe acne, regardless of age. Approximately half of pediatric or adolescent and adult participants achieved clear/almost clear skin with CAB, and lesion count reductions were >70 percent.
Funding/financial disclosures: Funding was provided by Ortho Dermatologics.
Atopic dermatitis
Anchored matching-adjusted indirect comparison of the long-term maintenance of efficacy of tralokinumab and lebrikizumab
Presenters: Matthias Augustin,1 April Armstrong,2 Naiem Issa,3–5 Anne Sohrt Petersen,6 Rie von Eyben,6 Teodora Festini,6 Tiago Torres7,8
Affiliations: 1University Medical Center Hamburg-Eppendorf (UKE), DE; 2University of Southern California, USA; 3Forefront Dermatology, USA; 4George Washington University School of Medicine and Health Sciences, USA; 5University of Miami Miller School of Medicine, USA; 6LEO Pharma A/S, DK; 7University of Porto, PT; 8Centro Hospitalar Universitário do Porto, PT.
Introduction: Tralokinumab and lebrikizumab are IL-13 inhibitors used to treat moderate-to-severe atopic dermatitis. No head-to-head studies have compared their efficacy to date. We conducted a matching-adjusted indirect comparison (MAIC) of the efficacy of tralokinumab and lebrikizumab at Week 52 in Week 16 responders.
Methods: A MAIC was performed using individual patient data from the ECZTRA 1&2 tralokinumab trials and aggregate data from the ADvocate 1&2 lebrikizumab trials. Endpoints were compared at Week 52 in patients who responded at Week 16, defined as patients achieving a 75 percent reduction in the Eczema and Severity Index from baseline (EASI-75) or Investigator’s Global Assessment 0 or 1, with at least two-point improvement (IGA 0/1). In both ECZTRA 1 & 2 and ADvocate 1 & 2, 16-week responders were re-randomized to receive placebo or active treatment (either tralokinumab 300mg or lebrikizumab 250mg, respectively) every two weeks (Q2W), or every four weeks (Q4W), for the 36-week maintenance period. During the maintenance period, patients who received rescue medication, discontinued treatment, or transferred to the escape arm were imputed as nonresponse for binary endpoints and imputed as last observation carried forward for continuous endpoints. Patients in the ECZTRA trials were weighted to match those of the ADvocate trials based on the following baseline characteristics: age, sex, ethnicity, body mass index (BMI), mean AD duration, proportion with IGA=3, mean EASI, mean worst daily pruritus numeric rating scale (pruritus NRS); and Week 16 characteristics: mean EASI, proportion of IGA 0/1 response, and mean pruritus NRS. The efficacy of tralokinumab and lebrikizumab relative to placebo at Week 52 were compared for the Q2W arms and Q4W arms, respectively. The efficacy outcomes analyzed include IGA 0/1, EASI-75, EASI-90, pruritus NRS 4-point improvement (pruritus 4pt), and EASI percentage change from baseline (CfB). A sensitivity analysis was made by comparing the analyses generated by using the two estimands reported in the ADvocate 1 & 2 trials.
Results: Tralokinumab had comparable efficacy to lebrikizumab across all endpoints. The results for the Q2W endpoints were numerically in favor of tralokinumab, though none of the results were statistically significant for both doses. Risk differences for the outcomes for the Q2W arms were IGA 0/1: 1.2 percent (p=0.94), EASI-75: 19.8 percent (p=0.13), EASI-90: 1.5 percent (p=0.91), pruritus 4pt: 17.6 percent (=0.34), and EASI CfB: 3.3 percent (p=0.46). Risk differences for the outcomes for the Q4W arms were IGA 0/1: -20.5 percent (p=0.22), EASI-75: 15.7 percent (p=0.23), EASI-90: -8.5 percent (p=0.51), pruritus 4pt: -2.7 percent (p=0.88), and EASI CfB: -0.5 percent (p=0.91). Sensitivity analysis showed similar outcomes.
Conclusion: Within the limitations of MAIC, comparable maintenance of efficacy was observed between tralokinumab and lebrikizumab after 52 weeks of treatment in 16-week responders.
Funding/financial disclosures: Funding was provided by by LEO Pharma A/S.
Delgocitinib cream reduces itch and pain in adults with moderate-to-severe chronic hand eczema: pooled analyses of the Phase 3 DELTA-1 and -2 trials
Presenters: Andrea Bauer,1 Marie-Louise Schuttelaar,2 Keith Baranowski,3 Ursula Plohberger,3 Laura Sørensen,3 Margitta Worm4
Affiliations: 1Department of Dermatology, University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; 2University Medical Centre Groningen, University of Groningen, The Netherlands; 3LEO Pharma A/S, Ballerup, Denmark; 4Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité Universitätsmedizin Berlin, Germany
Introduction: Itch and pain are two of the most common and burdensome symptoms of chronic hand eczema. Delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in primary and all secondary efficacy endpoints in DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101). The objectives of this analysis were to assess the effect on itch and pain of twice-daily applications of delgocitinib cream 20mg/g, including early onset of reductions, compared with cream vehicle in the treatment of adults with moderate-to-severe CHE in a pooled analysis of the pivotal Phase 3 DELTA-1 and DELTA-2 trials.
Methods: This analysis includes pooled data from DELTA-1 and -2 (delgocitinib cream 20mg/g [n=639]; cream vehicle [n=321]; twice-daily). The Hand Eczema Symptom eDiary (HESD) captured patient-reported worst severity of itch and pain over the past 24 hours on an 11-point numeric rating scale (0=no itch/pain to 10=severe itch/pain). Changes in itch and pain from baseline were assessed daily during Week (W)1 and weekly from W1–16.
Results: For itch, a significant least square (LS) mean reduction from baseline was detected one day after patients first applied delgocitinib 20mg/g (0.75) versus the cream vehicle group (0.32, p<0.001). For pain, a significant LS mean reduction was detected three days after the first application of delgocitinib cream (0.98) versus cream vehicle (0.58, p<0.001). The LS mean itch and pain reductions continued for delgocitinib cream-treated patients up to W16 (p<0.001). A clinically meaningful ≥4-point reduction in itch was achieved by significantly more patients applying delgocitinib cream from W2 (14.2%) versus cream vehicle (6.3%, p<0.001) and onwards to W16 (delgocitinib cream: 47.2%; cream vehicle: 21.5%; p<0.001). Similar results for a at least a four-point reduction in pain were observed.
Conclusion: Early onset of itch and pain reduction was observed within W1 for delgocitinib-treated patients, with reductions remaining significantly greater versus cream vehicle-treated patients from W1 to W16.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
DELTA FORCE trial: 24-week Phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe chronic hand eczema
Presenters: Ana Maria Giménez-Arnau,1 Andreas Pinter,2 Wiebke Sondermann,3 Ziad Reguiai,4 Richard Woolf,5 Charles Lynde,6 Franz J. Legat,7 Antonio Costanzo,8 Juan Francisco Silvestre,9 Berith Fredsted Hagen,10 Natja Mellerup,10 Ursula Plohberger,10 Lasse Ryttig,10 Andrea Bauer,11
Affiliations: 1Hospital Del Mar Research Institute, Universitat Pompeu Fabra, Spain; 2Goethe-Universität Frankfurt am Main, Germany; 3University Hospital Essen, Germany; 4Polyclinique Courlancy, France; 5King’s College London, UK; 6Lynde Institute for Dermatology, Lynderm Research, University of Toronto, Canada; 7Medical University of Graz, Austria; 8Humanitas University, Italy; 9Hospital General Universitario Dr Balmis, ISABIAL, Spain; 10LEO Pharma A/S, Denmark; 11University Allergy Center, University Hospital Carl Gustav Carus, Technical University Dresden, Germany
Introduction: In patients with moderate-to-severe chronic hand eczema (CHE), delgocitinib cream, a topical pan-Janus kinase inhibitor, demonstrated significant improvement in key efficacy endpoints and was well tolerated versus cream vehicle in Phase 3 DELTA 1 (NCT04871711), DELTA 2 (NCT04872101) and open label DELTA 3 (NCT04949841). The aim of this Phase 3 DELTA FORCE trial (NCT05259722) was to compare the efficacy, effect on health-related QoL, and safety of twice-daily topical delgocitinib cream (20mg/g) with once-daily oral alitretinoin in adults with severe CHE.
Methods: DELTA FORCE was a randomized, assessor-blind, active-controlled, multi-site trial. Adults (≥18 years) with severe CHE were randomized 1:1 to delgocitinib cream (n=254) or oral alitretinoin (n=259) for 24 weeks. The primary endpoint was change in HECSI from baseline to Week (W)12. Secondary endpoints included HECSI-90 and IGA-CHE treatment success (TS) at W12, (IGA-CHE 0/1 [clear/almost clear]), change in HESD itch/pain from baseline to W12, area under the curve (AUC) for HECSI-90 and the change in DLQI, and change in HECSI from baseline to W24. Safety endpoints included numbers of AEs, SAEs, and AEs leading to trial drug discontinuation.
Results: A significantly greater LS mean decrease in HECSI from baseline to W12 was observed with delgocitinib cream (67.6) versus alitretinoin (51.5; p<0.001). At W12, greater proportions of patients treated with delgocitinib cream versus alitretinoin achieved HECSI-90 (38.6% vs 26.0%; p=0.003) and IGA-CHE TS (27.2% vs 16.6%; p=0.004). Greater LS mean decreases from baseline were observed with delgocitinib cream versus alitretinoin in HESD itch/pain at W12 (3.0/2.9 vs 2.4/2.3; p≤0.018) and HECSI at W24 (69.6 vs 45.1; p<0.001); LS mean AUC for HECSI-90 (49.2 vs 34.9; p<0.001) and AUC for change in DLQI (1124.7 vs 790.7; p<0.001) were higher with delgocitinib cream versus alitretinoin. Fewer patients in the delgocitinib cream group than in the alitretinoin group reported AEs (number of events [E]=280 in 125 [49.4%] patients vs. E=620 in 188 [76.1%] patients), SAEs (E=5 in 5 [2.0%] patients vs. E=12 in 12 [4.9%] patients), and AEs leading to trial drug discontinuation (E=4 in 3 [1.2%] patients vs. E=44 in 25 [10.1%] patients).
Conclusion: Delgocitinib cream 20mg/g demonstrated superior treatment effects, QoL improvements, and a more favorable safety profile versus oral alitretinoin over 24 weeks, supporting its benefit in patients with severe CHE.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema: pooled results of the Phase 3 DELTA-1 and -2 trials
Presenters: Robert Bissonnette,1 Margitta Worm,2 Richard B Warren,3,4 Tove Agner,5 Melinda Gooderham,6,7 Marie Louise Schuttelaar,8 Keith Baranowski,9 Ursula Plohberger,9 Laura Soerensen,9 Sibylle Schliemann10
Affiliations: 1Innovaderm Research, Montreal, Quebec, CA; 2Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité Universitätsmedizin Berlin, DE; 3Dermatology Centre, Northern Care Alliance NHS Foundation Trust; 4NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, UK; 5Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, DK; 6Department of Dermatology, Queens University, Peterborough, Ontario, CA; 7SKiN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, CA; 8University Medical Centre Groningen, University of Groningen, NL; 9LEO Pharma A/S, Ballerup, DK; 10Department of Dermatology, University Hospital Jena, Jena, Germany
Introduction: Chronic hand eczema (CHE) is a frequent inflammatory skin disease associated with pain, pruritus, and significant occupational, functional, social, and psychological burden. Delgocitinib is a topical pan-JAK inhibitor that showed a dose-dependent efficacy in adults with CHE in a Phase 2b trial. The objectives of this analysis were to study (1) the efficacy of twice-daily applications of delgocitinib cream 20mg/g, as assessed by Investigator’s Global Assessment for CHE treatment success (primary outcome), and the secondary outcomes ≥75%/≥90% improvement in Hand Eczema Severity Index and at least a four-point improvement in the Dermatology Life Quality Index, and (2) the safety of twice-daily applications of delgocitinib cream 20mg/g compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the DELTA-1 and DELTA-2 trials.
Methods: In the Phase 3 DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials, adults with moderate-to-severe CHE were randomized 2:1 to twice-daily delgocitinib cream 20mg/g or cream vehicle for 16 weeks. The primary endpoint was the Investigator’s Global Assessment for CHE (IGA-CHE) treatment success at Week 16, defined as IGA-CHE score of 0/1 (clear/almost clear, i.e., no/barely perceptible erythema and no other signs), with at least a two-step improvement from baseline. Key secondary endpoints included ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) and at least a four-point improvement in the Dermatology Life Quality Index (DLQI). This DELTA-1 and -2 pooled analysis included 639 patients treated with delgocitinib cream and 321 with cream vehicle.
Results: At Week 16, a significantly greater proportion of delgocitinib-treated patients, versus cream vehicle, achieved IGA-CHE treatment success (24.3% vs. 8.4%; p<0.001), HECSI-75 (49.4% vs. 20.9%; p<0.001), HECSI-90 (30.3% vs. 10.6%; p<0.001), and DLQI ≥4-point improvement (73.3% vs. 47.8%; p<0.001). Most frequent adverse events (occurring in ≥5% of patients) were COVID-19, nasopharyngitis, and headache with similar rates in both treatment groups.
Conclusion: In the DELTA-1 and -2 pooled analysis, delgocitinib cream twice-daily confirmed its clinical efficacy in patient- and clinician-reported efficacy outcomes versus cream vehicle in adult patients with CHE and suggests an innovative treatment option in this often difficult-to-treat patient population.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Lebrikizumab improves atopic dermatitis and quality of life in patients with moderate-to-severe atopic dermatitis previously treated with dupilumab: Results from the ADapt trial
Presenters: Jonathan I. Silverberg,1 Lindsay Ackerman,2 Jerry Bagel,3 Linda Stein Gold,4 Andrew Blauvelt,5 David Rosmarin,6 Raj Chovatiya,7 Matthew Zirwas,8 Gil Yosipovitch,9 Jill Waibel,10 Jenny E. Murase,11 Ben Lockshin,12 Jamie Weisman,13 Amber Reck Atwater,14 Cynthia Harris,14 Jennifer Proper,14 Maria Silk,14 Evangeline Pierce,14 Maria Lucia Buziqui Piruzeli,14 Sonia Montmayeur,14 Christopher Schuster,14 Jinglin Zhong,15 Maria Jose Rueda,14 Sreekumar Pillai,14 Eric Simpson,15
Affiliations: 1George Washington University School of Medicine and Health Sciences, Washington, DC; 2U.S. Dermatology Partners, Phoenix, AZ; 3Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 4Henry Ford Hospital, Detroit, MI; 5Blauvelt Consulting, LLC, Portland, OR; 6Indiana University School of Medicine Indianapolis, IN; 7Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL; 8Dermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH; 9University of Miami Miller School of Medicine, Miami, FL; 10Miami Dermatology and Laser Institute, Miami, FL; 11Department of Dermatology, University of California, San Francisco, San Francisco, CA; and Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View, CA; 12DermAssociates, Silver Spring, MD; 13Medical Dermatology Specialists, Atlanta, GA; 14Eli Lilly and Company, Indianapolis, IN; 15IQVIA, Durham, NC; 15Oregon Health & Science University, Portland, OR
Introduction: ADapt (NCT05369403), an open-label, Phase 3b, 24-week study, evaluated the efficacy and safety of lebrikizumab (LEB) in patients with moderate-to-severe atopic dermatitis (AD) previously treated with dupilumab (DUPI). Patients must have discontinued DUPI due to inadequate response (non-response, partial response, or loss of response), intolerance or an adverse event (AE), or other reasons.
Methods: Four or more weeks after discontinuing DUPI, patients received a 500mg LEB loading dose at baseline and at Week 2 followed by 250mg every two weeks through Week 16 (Q2W). At Week 16, responders (IGA 0 or 1 with ≥2-point improvement [IGA0,1] or EASI75 [primary endpoint]) received LEB 250mg once every four weeks (Q4W); other patients continued with 250mg Q2W. Q2W and Q4W data were pooled and analyzed as-observed and with nonresponder/multiple imputation (NRI/MI).
Results: Among 86 enrolled patients, 56 percent discontinued DUPI due to inadequate response, 16 percent due to intolerance/AEs to DUPI, and 28 percent for other reasons. For all patients, at Weeks 16 and 24, respectively, proportions of patients achieving: 1) EASI75: 57.4 percent and 60.0 percent, as-observed; 50.7 percent and 52.8 percent NRI/MI; 2) IGA0,1: 38.7 percent and 38.2 percent, as-observed; 35.6 percent and 36.8 percent, NRI/MI; 3) Face-IGA 0: 42 percent and 49 percent, as-observed; 4) Pruritus NRS ≥4-point improvement 53.2 percent and 61.5 percent as-observed; 48.8 percent and 47.9 percent NRI/MI; and 5) DLQI ≥4-point improvement 83.0 percent and 83.0 percent as-observed. The safety profile was consistent with other LEB Phase 3 trials. Four patients who discontinued DUPI due to conjunctivitis did not report conjunctivitis with LEB. Additionally, 3.5 percent of patients reported treatment-emergent conjunctivitis.
Conclusion: In DUPI-experienced patients, treatment of moderate-to-severe AD with LEB resulted in meaningful improvements in skin clearance, itch, and quality of life.
Funding/financial disclosures: Funding was provided by Eli Lilly and Company.
Long-term safety and efficacy of tralokinumab in adults and adolescents with moderate-to-severe atopic dermatitis treated for up to 6 years
Presenters: Andrew Blauvelt,1 Vivian Laquer,2 Richard G. Langley,3 H. Chih-ho Hong,4 Christian Bjerregård Øland,5 Le Gjerum,5 Ann-Marie Tindberg,5 Kristian Reich,6
Affiliations: 1Blauvelt Consulting, LLC, Portland, OR, US; 2First OC Dermatology Research, Fountain Valley, CA, US; 3Dalhousie University, Halifax, NS, CA; 4Dr. Chih-ho Hong Medical Inc., Surrey, BC, CA; 5LEO Pharma A/S, Ballerup, DK; 6University Medical Center Hamburg-Eppendorf, Hamburg, DE
Introduction: Tralokinumab, a monoclonal antibody that specifically neutralizes interleukin13, is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in patients of at least 12 years of age. ECZTEND (NCT03587805) is an open-label extension study evaluating the long-term safety and efficacy of tralokinumab in patients with moderate-to-severe AD. Interim analyses previously demonstrated the benefit-risk profile of tralokinumab in patients followed up to 3.5 years in ECZTEND; here, we present the final study results.
Methods: Patients completing any of nine parent trials (ECZTRA 1-8 and the TraSki investigator-initiated study) were able to enter ECZTEND. Patients in ECZTEND received tralokinumab 300mg every other week, with topical corticosteroids and/or calcineurin inhibitors allowed. The primary objective of ECZTEND was to assess safety of tralokinumab treatment from baseline up to Week 268. Secondary objectives were to assess efficacy, including proportions of patients achieving Investigator’s Global Assessment score of 0 or 1 (IGA 0/1; clear/almost clear skin) or at least 75 percent improvement in Eczema Area and Severity Index (EASI-75) from parent trial baseline, and quality of life (QoL) measures up to Week 248.
Results: In total, 1,672 patients were treated with tralokinumab for up to 5.1 years in ECZTEND. Median exposure was 2.6 years, with 4466.2 total patient years of exposure. Maximum tralokinumab exposure, including the parent trial period, was 6.1 years. In ECZTEND, exposure-adjusted incidence rate (IR) of patients with at least one treatment-emergent adverse event (AE) was 114.3, which was lower than the initial 16-week treatment period of the parent trials (IR=424.8 for tralokinumab; IR=475.3 for placebo). Over five years of ECZTEND, serious AEs were reported in 9.0 percent of patients (IR=3.54). AEs that led to permanent discontinuation of treatment occurred in 4.5 percent of patients (IR=1.71). The most frequently reported AEs (≥5% of patients) were nasopharyngitis (22.2%), dermatitis atopic (21.4%), coronavirus infection (17.9%), upper respiratory tract infection (8.8%), headache (6.8%), and conjunctivitis (6.2%). Pre-defined AEs of special interest (eye disorders, skin infections requiring systemic treatment, eczema herpeticum, malignancies) were observed at rates similar to, or lower than, the initial treatment period of the parent trials. At Week 248, response rates (95% CI) for IGA 0/1 and EASI-75 were 66.7 percent (56.1-75.8) and 92.9 percent (85.396.7), respectively. Additionally, itch, sleep, and QoL improvements were sustained at levels equivalent to no-to-mild disease throughout ECZTEND.
Conclusion: Long-term use of tralokinumab, up to one year in parent trials plus up to five years in ECZTEND, was well-tolerated with no new safety signals identified in patients aged 12 years and up with moderate-to-severe AD. Tralokinumab treatment demonstrated robust long-term efficacy with sustained improvements in AD signs, symptoms, and QoL.
Funding/financial disclosures: Funding was provided by by LEO Pharma A/S.
Long-term safety and efficacy of delgocitinib cream for up to 36 weeks in adults with chronic hand eczema: results of the Phase 3 open-label extension DELTA-3 trial
Presenters: Melinda Gooderham,1,2 Sonja Molin,3 Robert Bissonnette,4 Margitta Worm,5 Marie-Noëlle Crépy,6,7 Luca Stingeni,8 Richard B Warren,9,10 Sibylle Schliemann,11 Cherry Lou Balita-Crisostomo,12 Marie Louise Oesterdal,12 Tove Agner,13
Affiliations: 1Queens University, Kingston, Ontario, CA; 2SKiN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, CA; 3Queen’s University, Kingston, Canada; 4Innovaderm Research, Montreal, Quebec, CA; 5Charité Universitätsmedizin Berlin, DE; 6University Hospital of Centre of Paris, Cochin Hospital, AP-HP, Paris, FR; 7University Hospital of Centre of Paris, Hôtel-Dieu Hospital, AP-HP, Paris, FR; 8University of Perugia, Perugia, IT; 9Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK; 10NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 11University Hospital Jena, Jena, DE; 12LEO Pharma A/S, Ballerup, DK; 13Bispebjerg Hospital, University of Copenhagen, Copenhagen, DK
Introduction: In patients with moderate to severe chronic hand eczema (CHE), delgocitinib cream, a topical pan-Janus kinase inhibitor, was well tolerated and demonstrated significant improvement in all efficacy endpoints in DELTA-1 and -2. The objectives of this study were to evaluate the long-term safety and efficacy of twice-daily applications of delgocitinib cream 20mg/g as needed for up to 36 weeks in adults with CHE in the Phase 3 open-label DELTA-3 trial (NCT04949841), an extension trial of the 16-week DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials.
Methods: In DELTA-3, subjects who completed the 16-week (W) treatment period in DELTA-1 and DELTA-2 were treated on an as-needed basis with twice-daily delgocitinib cream 20mg/g for 36 weeks (n=801). Subjects with Investigator’s Global Assessment for CHE (IGA-CHE) of at least two received delgocitinib cream until symptoms resolved (i.e., IGA-CHE 0/1 [clear/almost clear]). Primary endpoint was number of treatment-emergent adverse events (TEAEs). Key secondary endpoints were IGA-CHE 0/1 and ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) scores; Hand Eczema Symptom eDiary captured patient-reported worst severity of itch/pain over the past 24 hours.
Results: No safety concerns were identified during delgocitinib cream treatment in DELTA-1 (n=325; R=305.4; PYO=100.9), DELTA-2 (n=313; R=280.6; PYO=95.9) and DELTA-3 (n=801; R=231.1; PYO=535.7). In DELTA-3, the most frequent TEAEs were COVID-19 and nasopharyngitis. In DELTA-3, IGA-CHE 0/1, HECSI-75, HECSI-90 and at least a four-point itch/pain reduction were maintained from baseline (24.6%, 51.8%, 31.8%, and 50.6%/51.9%, respectively) to W36 (30.0%, 58.6%, 36.6%, and 52.4%/55.4%, respectively) among delgocitinib cream-treated subjects in the parent trials. Among those treated with cream vehicle in parent trials, response rates improved from baseline (9.1%, 23.7%, 12.0%, and 26.3%/32.3%, respectively) to W36 (29.5%, 51.5%, 35.7%, and 41.3%/43.3%, respectively).
Conclusion: Overall, with delgocitinib cream 20mg/g treatment no safety concerns were identified and efficacy further improved, supporting the benefit of long-term as-needed use of delgocitinib cream in patients with moderate-to-severe CHE.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Once-daily roflumilast cream 0.15% for the treatment of atopic dermatitis in patients with diverse skin types: pooled subgroup analysis from the Phase 3 INTEGUMENT-1 and-2 trials
Presenters: Vimal H. Prajapati,1 John C. Browning,2 Mercedes E. Gonzales,3 Chih-Ho Hong,4 Eric Simpson,5 Melissa S. Seal,6 David Krupa,6 Patrick Burnett,6 David R. Berk,6 Robert C. Higham,6 David H. Chu6
Affiliations: 1Dermatology Research Institute, Probity Medical Research, Skin Health & Wellness Centre, and University of Calgary, Calgary, AB, Canada; 2Texas Dermatology and Laser Specialists, San Antonio, TX, USA; 3Pediatric Skin Research, LLC Miami, FL, USA; 4Probity Medical Research and University of British Columbia, Surrey, BC, Canada; 5Oregon Health & Science University, Portland, OR, USA, 6Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA
Introduction: Once-daily topical roflumilast is a selective, highly potent phosphodiesterase 4 inhibitor approved for the treatment of atopic dermatitis (AD), psoriasis, and seborrheic dermatitis. Overall results from two Phase 3, randomized, controlled trials (INTEGUMENT-1: NCT04773587; INTEGUMENT-2: NCT04773600) in AD were reported previously. This pooled analysis of INTEGUMENT-1 and -2 reports efficacy of roflumilast cream 0.15% in patients with diverse skin types based on race, ethnicity, and Fitzpatrick skin type.
Methods: Patients (aged ≥6 years) with Validated Investigator Global Assessment for AD (vIGA-AD) of mild (2) or moderate (3) and body surface area affected by AD of at least three percent (no upper limit) were randomized 2:1 to roflumilast cream 0.15% or vehicle for four weeks.
Results: Overall, 59.5 percent of patients were White, 20.3 percent Black/African American, 13.2 percent Asian, 7.0 percent of other race, and 16.6 percent Hispanic/Latino; 53.8 percent had Fitzpatrick skin type I–III and 46.2 percent had type IV–VI. At Week 4, vIGA-AD Success (Clear [0] or Almost Clear [1] with ≥2-grade improvement) was achieved by 31.3 percent of the roflumilast group and 14.1 percent of the vehicle group (p<0.0001). Proportions with vIGA-AD Success were greater for roflumilast versus vehicle regardless of race (White: 32.3% vs. 13.3%; Black/African American: 25.8% vs. 11.5%; Asian: 33.7% vs. 21.8%; other race: 33.2% vs. 13.7%), ethnicity (Hispanic/Latino: 32.9% vs. 16.5%; not Hispanic/Latino: 31.1% vs. 13.8%), or Fitzpatrick skin type (I–III: 33.0% vs. 13.4%; IV–VI: 29.2% vs. 14.8%). Greater proportions treated with roflumilast versus vehicle also achieved Worst Itch-Numeric Rating Scale (WI-NRS) success (≥4-point improvement in patients with baseline WI-NRS ≥4) at Week 4 (31.9% vs. 16.6%; p<0.0001), with consistent results regardless of subgroup (White: 33.5% vs. 16.5%; Black/African American: 30.6% vs. 21.0%; Asian: 25.4% vs. 7.9%; other race: 34.3% vs. 22.7%; Hispanic/Latino: 37.4% vs. 30.5%; not Hispanic/Latino: 30.9% vs. 13.8%; Fitzpatrick skin type I–III: 35.5% vs. 15.0%; Fitzpatrick skin type IV–VI: 27.3% vs. 18.2%). Similar findings were observed for vIGA-AD 0/1 and at least a 75-percent improvement in Eczema Area and Severity Index. The incidence of treatment-emergent adverse events (TEAEs) was low for both roflumilast and vehicle, and generally similar across subgroups. Local tolerability was also similar.
Conclusion: Roflumilast cream 0.15% provided consistent and meaningful improvements in signs and symptoms of AD in patients across race, ethnicity, and Fitzpatrick skin types.
Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patients with atopic dermatitis with hands and feet involvement after up to 9 months of treatment in the TRACE study
Presenters: Diamant Thaçi,1 Pierre André Becherel,2 Adrian Rodriguez,3 Teodora Festini,4 Ulla Ivens,4 Ida Vittrup,4 Mahreen Ameen5
Affiliations: 1University of Luebeck, Germany, 2Antony Hospital, France, 3Nashville Skin, USA, 4LEO Pharma A/S, DK, 5Royal Free London National Health Services Foundation Trust, UK
Introduction: AD is a chronic skin disease often affecting hands and/or feet (H&F), which are considered high-impact areas due to significant negative impact on QoL and ability to work. Tralokinumab, a monoclonal antibody specifically targeting interleukin-13, is indicated for treatment of moderate-to-severe AD. Here, we evaluated the impact of tralokinumab in patients with H&F AD in an interim analysis (IA) of the noninterventional TRACE study.
Methods: TRACE is an international, prospective, single-cohort study of adult patients with AD (enrolled November 2021 to July 2023) that were prescribed tralokinumab according to national approved labels. At IA data cut-off (Oct. 15, 2023), not all patients had completed all visits. This analysis included patients with AD involvement on H&F at baseline. Outcomes collected included AD localization, and overall AD measures, IGA, DLQI, RECAP, WPAI, Peak Pruritus NRS (PP-NRS), and/or Sleep NRS according to individual clinical practice. Data presented as observed.
Results: Among patients who had H&F AD at baseline (59.8% of full analysis set), 42.4 percent (175/413) had no H&F AD at three months (M), which increased to 53.3 percent at 9M. Percentages with IGA 0/1 increased from 0.8 percent (4/488) at baseline to 32.7 percent (127/388) at 3M, 45.1 percent (92/204) at 6M, and 60.9 percent (56/92) at 9M of tralokinumab. The percentages of patients with IGA 4 decreased from 37.9 percent (185/488) at baseline to 5.2 percent (20/388) at 3M, 3.9 percent (8/204) at 6M, and 3.3 percent (3/92) at 9M. Among patients with baseline IGA≥2, percentages achieving at least a two-point improvement in IGA increased from 45.4 percent (164/361) at 3M to 55.4 percent (108/195) at 6M, and 74.7 percent (65/87) at 9M. Among patients with baseline DLQI≥6, majority achieved at least a six-point reduction in DLQI with tralokinumab: 59.2 percent (71/120) at 3M, 60.0 percent (39/65) at 6M, and 71.1 percent (27/38) at 9M. In patients with H&F AD, the mean percent overall work impairment due to AD decreased from 29.7 percent (n=87) at baseline to 16.7 percent (n=50) at 3M, 13.6 percent (n=20) at 6M, and 15.2 percent (n=15) at 9M. Mean PP-NRS improved from 6.5 (n=275) at baseline to 4.4 (n=165) at 3M, 3.5 (n=92) at 6M, and 3.4 (n=54) at 9M. Mean Sleep NRS improved from 5.3 (n=215) at baseline to 2.8 (n=128) at 3M, 2.5 (n=68) at 6M, and 2.3 (n=49) at 9M of tralokinumab. Similar improvements were observed across endpoints in both dupilumab-naive (n=383) and dupilumab experienced (n=110) patients, despite higher baseline disease severity in dupilumab-naive patients.
Conclusion: Treatment for 9M with tralokinumab cleared H&F AD in more than 50 percent of patients. Tralokinumab also improved signs, symptoms, QoL, and work productivity in patients with H&F AD in a real-world setting. Dupilumab-naive and dupilumab-experienced patients demonstrated similar improvements with tralokinumab.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in patients with head and neck atopic dermatitis after up to 9 months of treatment in the TRACE study
Presenters: April Armstrong,1 Ahmed Ameen,2 Jerry Bagel,3 Teodora Festini,4 Ulla Ivens,4 Ida Vittrup,4 Andrew E. Pink5
Affiliations: 1University of California Los Angeles, USA; 2NMC Speciality Hospital, UAE; 3Windsor Dermatology, USA; 4LEO Pharma A/S, DK; 5St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospitals, UK
Introduction: AD is a chronic skin disease affecting multiple areas, including the head and neck (H&N) region, reported in 72 percent of patients with moderate-to-severe AD. H&N AD, in particular, is associated with social embarrassment, stigmatization, and negative impact on patients’ QoL and mental health. Tralokinumab, a monoclonal antibody specifically targeting interleukin-13, is indicated for treatment of moderate-to-severe AD. Here, we evaluated the effectiveness of tralokinumab in patients with H&N AD in an interim analysis (IA) of the non-interventional TRACE study.
Methods: TRACE is an international, prospective, single-cohort study of adult patients with AD (enrolled between November 2021 and July 2023) prescribed tralokinumab according to national approved labels. At IA data cut-off (Oct. 15, 2023), not all patients had completed all visits. This analysis included patients with AD involvement on face, scalp, and neck at baseline. Outcomes collected included AD localization, and overall AD measures, including IGA, DLQI, RECAP, Peak Pruritus NRS (PP-NRS), and/or Sleep NRS per individual clinical practice. Data are presented as-observed.
Results: In patients with H&N AD at baseline (79.5% of full analysis set), the percentages that still reported AD on the H&N area decreased to 67.2 percent (363/540) at three months (M) and to 52.1 percent at 9M. Percentage with IGA 0/1 increased from 1.4 percent (9/650) at baseline to 33.6 percent (172/512) at 3M, 48.4 percent (121/250) at 6M, and 57.4 percent (58/101) at 9M of tralokinumab. The percentages of patients with IGA 4 decreased from 37.7 percent (245/650) at baseline to 4.7 percent (24/512) at 3M, 2.8 percent (7/250) at 6M, and 2.0 percent (2/101) at 9M. Among patients with baseline IGA≥2, the percentages achieving at least a two-point improvement in IGA increased from 46.4 percent (220/474) at 3M to 59.1 percent (140/237) at 6M, and 71.6 percent (68/95) at 9M. Among patients with baseline DLQI≥6, the majority achieved at least a six-point reduction in DLQI with tralokinumab: 57.9 percent (84/145) at 3M, 63.6 percent (49/77) at 6M, and 74.4 percent (32/43) at 9M. Mean PP-NRS improved from 6.4 (n=387) at baseline to 4.2 (n=213) at 3M, 3.5 (n=111) at 6M, and 3.3 (n=59) at 9M. Mean Sleep NRS improved from 5.2 (n=305) at baseline to 2.8 (n=170) at 3M, and 2.3 at 6M and 9M (n=84 and n=53, respectively) of tralokinumab. Similar improvements were observed across endpoints in both dupilumab-naive (n=154) and dupilumab-experienced (n=501) patients, despite higher baseline disease severity in dupilumab-naive patients.
Conclusion: Up to 9M of tralokinumab treatment in a real-world setting reduced H&N involvement and improved disease severity and QoL in patients with AD in the difficult to treat H&N area; all improvements were similar regardless of prior dupilumab use.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Real-world effectiveness of tralokinumab in adults with atopic dermatitis on the genitals: Interim data on improvements in physician-assessed disease severity and patient-reported outcomes in up to 3 months of treatment in the TRACE study
Presenters: Esther Serra-Baldrich,1 April W. Armstrong,2 Teodora Festini,3 Ulla Ivens,3 Ida Vittrup,3 Marni Wiseman,4
Affiliations: 1Universitat Autonoma de Barcelona, ES; 2University of California Los Angeles, USA; 3LEO Pharma A/S, DK; 4Skinwise Dermatology, California
Introduction: Atopic dermatitis (AD) can involve any part of the skin, including the genital region. Presentation of AD on genitals is often overlooked/underreported due to reluctance to discuss this sensitive area with clinicians and lack of routine examination of this region. To successfully treat all body regions with AD, increased awareness of AD involvement in underreported sites is needed. Tralokinumab, a monoclonal antibody that specifically targets interleukin-13, is indicated for treatment of moderate-to-severe AD. Phase 3 trials have shown tralokinumab is effective and well-tolerated, and recent case series demonstrated successful use of dupilumab and tralokinumab for AD on the genitals. Here, we evaluated changes in disease severity and patient-reported outcomes (PROs) in patients with AD on the genitals in an interim analysis (IA) of the TRACE study.
Methods: TRACE is a prospective, noninterventional, international, single-cohort study of adults with AD prescribed tralokinumab according to national approved labels. Patients were enrolled between November 2021 and July 2023, with IA data cut-off of October 15, 2023.
Only patients with AD on the genitals were included. Outcome measures collected included: IGA, DLQI, and sleep numerical rating scale (NRS), as per individual clinical practice.
Results: At baseline, 14.9 percent of patients in the full analysis set (FAS) had AD on the genitals (n=123/824); these patients had a mean age of 42.2 years, mean AD duration of 19.2 years, and the majority were male (63.4%) and White (81.3%). Baseline characteristics were similar to FAS, though a greater proportion of patients with AD on the genitals were male (52.2% in FAS), White (75.7% in FAS), and in Europe. Among patients with AD on genitals at baseline, 25 percent of patients reported AD on genitals at three months (n=100). Proportion of patients with IGA 0/1 increased from 0.0 percent at baseline (n=122) to 31.9 percent at 3 months (n=94). Proportion of patients with IGA 4 decreased from 49.2 percent at baseline (n=122) to 7.4 percent at three months (n=94). Among patients with IGA≥2 at baseline, 48.9 percent achieved IGA≥2-point improvement at three months (n=90). Among patients with DLQI≥6 at baseline, DLQI≥6-point improvement was achieved in 63.6 percent of patients at three months (n=22). Mean sleep NRS decreased from 6.2 at baseline (n=50) to 3.5 at three months (n=26). Overall, improvements in physician-assessed outcomes and PROs were similar in patients with AD on the genitals compared to FAS.
Conclusion: Increasing awareness of the impact of AD on the genitals and available treatment options for this neglected area is crucial. IA results (up to 3 months) of TRACE show effectiveness and improvements in PROs with tralokinumab in adults with AD on genitals in a real-world setting.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Real-world effectiveness of tralokinumab in adults with atopic dermatitis: Interim data on improvements in physician-assessed disease severity after up to 9 months of follow-up in the TRACE study
Presenters: Elena Pezzolo,1,2 Michael Cork,3,4 Jennifer Beecker,5 Adrian Rodriguez,6 Niels Bennike,7 Teodora Festini,7 Ulla Ivens,7 Diamant Thaçi8
Affiliations: 1San Bortolo Hospital, Italy; 2A Study Centre of the Italian Group for the Epidemiologic Research in Dermatology (GISED), Italy; 3Sheffield Children’s Hospital, UK; 4University of Sheffield, UK; 5The Ottawa Hospital Research Institute, Canada; 6Nashville Skin, USA; 7LEO Pharma A/S, Denmark; 8University of Lübeck, Germany
Introduction: Tralokinumab, a monoclonal antibody specifically targeting interleukin-13, is indicated for treatment of moderate-to-severe AD. Phase 3 clinical trials have shown tralokinumab is effective and well-tolerated, and real-world data are becoming available. Here, we evaluated changes in investigator-assessed AD disease severity in an interim analysis (IA) of the noninterventional TRACE study.
Methods: TRACE is a prospective, international, single-cohort study of adults with AD (enrolled between November 2021 and July 2023) who were prescribed tralokinumab according to national approved labels. At IA data cut-off (October 15, 2023), the following number of patients were included in the full analysis set (FAS): baseline (n=824), three months (n=668), six months (n=331), and nine months (n=143). Outcome measures collected included: Body Surface Area (BSA), EASI, and/or IGA), as per individual clinical practice.
Results: At baseline, patients had mean age of 44.1 years, mean AD duration of 18.9 years, more than half were male (52.2%), and the majority were White (75.7%). Regarding prior AD treatments at baseline (n=818), 42.7 percent of patients were categorized as “systemic and biologic naïve,” 32.4 percent as “systemic user but biologic naïve” and 24.9 percent as “biologic user,” with 23.9 percent dupilumab-experienced. For the FAS, mean EASI improved from 20.1 at baseline (n=631) to 6.4 at three months (n=482), 5.4 at six months (n=212), and 3.6 at nine months (n=88). Proportion of patients with EASI≤7 (no-or-mild disease), increased from 14 percent at baseline (n=631) to 72 percent at three months (n=482), 77 percent at six months (n=212), and 80 percent at 9 months (n=88). Proportion of patients with IGA 4 decreased from 34.0 percent at baseline (n=808) to 4.6 percent at three months (n=632), 2.7 percent at six months (n=298), and 2.5 percent at nine months (n=120). Among patients with IGA≥2 at baseline, the proportion achieving at least a two-point improvement in IGA increased from 46 percent at three months (n=566) to 58 percent at six months (n=279) and 70 percent at nine months (n=112). Mean BSA improved from 28.5 percent at baseline (n=689) to 12.1 percent at three months (n=528), 9.3 percent at six months (n=262), and 7.6 percent at nine months (n=105). In dupilumab-experienced patients, mean EASI decreased from 16.9 at baseline (n=132) to 6.8 at three months (n=92), 5.9 at six months (n=41), and 3.8 at nine months (n=20). The proportion of dupilumab-experienced patients with EASI≤7 increased from 26 percent at baseline (n=132) to 70% at three months (n=92), 76 percent at six months (n=41), and 80 percent at nine months (n=20).
Conclusion: The IA of TRACE showed effectiveness of tralokinumab treatment in adult patients with AD in a real-world setting.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
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
Presenters: Robert Bissonnette,1 Linda Stein Gold,2 Leon Kircik,3 Eric Simpson,4 Lawrence F. Eichenfield,5 John Browning,6 Adelaide A. Hebert,7 Andrew F. Alexis,8 Weily Soong,9 Stephen C. Piscitelli,10 Anna M. Tallman,10 David S. Rubenstein,10 Philip M. Brown,10 Jonathan I. Silverberg11
Affiliations: 1Innovaderm Research Inc., Montreal, QC, Canada; 2Henry Ford Health System, Detroit, MI, USA; 3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Oregon Health & Science University, Portland, OR, USA; 5University of California San Diego and Rady Children’s Hospital, San Diego, CA, USA; 6UTHealth San Antonio, TX, USA; 7UTHealth McGovern School of Medicine and Children’s Memorial Hermann Hospital, Houston, TX, USA; 8Weill Cornell Medical College, New York, NY, USA; 9AllerVie Health and Clinical Research, Birmingham, AL, USA; 10Dermavant Sciences, Inc., Morrisville, NC, USA; 11The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
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 four-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, 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 vIGAAD™≥1 were treated with tapinarof until complete clearance (vIGA-AD™=0). 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: In total, 728 patients enrolled; 83.0 percent were pediatric (2–17 years). Overall, 51.9 percent (378/728) achieved complete disease clearance, and 81.6 percent 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.
Conclusion: 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.
Funding/financial disclosures: Funding was provided by Dermavant Sciences, Inc.
Systemic exposure and safety profile of delgocitinib cream in adults with moderate to severe chronic hand eczema in the Phase 3 DELTA-2 trial
Presenters: Melinda Gooderham,1,2 Diamant Thaçi,3 Tina Damgaard,4 Daniel Madsen,4 Anders Soehoel,4 Robert Bissonnette5
Affiliations: 1Department of Dermatology, Queens University, Peterborough, Ontario, Canada; 2SKiN Centre for Dermatology and Probity Medical Research, Peterborough, Ontario, Canada; 3Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 4LEO Pharma A/S, Ballerup, Denmark; 5Innovaderm Research, Montreal, Quebec, Canada
Introduction: In the DELTA-2 (NCT04872101) Phase 3 trial, delgocitinib cream 20mg/g, a topical pan-Janus kinase inhibitor, was well-tolerated and demonstrated significant improvement in all efficacy endpoints versus cream vehicle in adults with moderate to severe chronic hand eczema (CHE). The objectives of this analysis were (1) to examine systemic exposure of delgocitinib cream 20mg/g in adults with moderate-to-severe CHE in the randomized, double-blind, vehicle-controlled DELTA-2 trial (2) to compare the DELTA-2 systemic exposure with corresponding data following oral administration of delgocitinib in a Phase 1 trial, (3) to present a summary of safety related to delgocitinib cream from the randomized, double-blind, vehicle-controlled DELTA-2 trial.
Methods: Pharmacokinetic blood sampling in DELTA-2 was performed 2 to 6 hours after delgocitinib application at Weeks 1, 4, and 16 using a liquid chromatography/mass spectrometrybased method (lower limit of quantitation: 5pg/mL). In the Phase 1 trial (NCT05050279), single oral doses of delgocitinib were tested in healthy volunteers with sampling performed for up to 24 hours post-administration.
Results: In DELTA-2, minimal systemic exposure was recorded in 313 delgocitinib-treated patients, with the highest geometric mean plasma concentration being 0.21ng/mL at Week 1 (n=286). In the Phase 1 trial, the lowest oral delgocitinib dose tested (1.5 mg; n=8) is regarded as subtherapeutic and showed a peak systemic exposure (geometric mean Cmax) of 7.2ng/mL. In DELTA-2, adverse events (AEs) were reported by 45.7 percent (n=143/313; delgocitinib cream) and 44.7 percent (n=71/159; cream vehicle) of patients, with COVID-19 being most common (11.5% vs 12.6%, respectively). The rate of possibly or probably related AEs was low and similar between delgocitinib cream and cream vehicle. No deaths were reported. Few serious AEs were reported with none assessed as related to the study drug.
Conclusion: The DELTA-2 trial demonstrated minimal systemic exposure in association with a favorable safety profile, supporting a lack of meaningful systemic effect from twice-daily applications of delgocitinib cream in patients with moderate-to-severe CHE.
Funding/financial disclosures: Funding was provided by LEO Pharma A/S.
Systemic therapy improves patient-reported treatment satisfaction, adherence, and reduces therapy burden in patients with atopic dermatitis: advanced practice provider and patient perspectives
Presenters: Eileen Cheever,1 Leigh Ann Panch,2 Douglas DiRuggiero,3 Sandri Johnson,4 Zach Dawson,5 Evangeline Pierce,5 Peter Anderson,6 James Piercy,6 Simran Marwaha,6 Jennifer Silva,7 Kirk Gautier,8
Affiliations: 1Clearview Dermatology, Leominster, USA; 2DOCS Dermatology, Cincinnati, USA; 3Skin Cancer & Cosmetic Dermatology, Rome, USA; 4Midtown Dermatology, Raleigh, USA; 5Eli Lilly and Company, Indianapolis, USA; 6Adelphi Real World, Bollington, UK; 7Central Connecticut Dermatology, Avon, USA; 8U.S. Dermatology partners, Dallas, USA.
Introduction: Despite therapeutic advances, patients with atopic dermatitis (AD) often face challenges with treatment adherence and satisfaction. This study evaluates dermatology advanced practice providers’ (APPs) perceptions of patients’ treatment challenges, and patients’ perceptions of treatment adherence and satisfaction in patients with a history of moderate-to-severe AD.
Methods: Data were obtained from the Adelphi AD Disease Specific Programme (February 2021–February 2022), a cross-sectional real-world study with retrospective data capture conducted in the U.S. involving APPs and their adult patients with AD. APPs provided data on patient demographics, disease characteristics, and issues with current treatment. Patients reported their current treatment satisfaction and completed Adelphi Adherence Questionnaire (ADAQ; 11-item, 0=complete adherence, 4=complete non-adherence). Patients were stratified based on current treatments (systemics±topicals and topicals only). Systemic treatments included injectable biologics, oral and injected corticosteroids, and conventional immunosuppressants. Topical treatments included corticosteroids, calcineurin inhibitors, and crisaborole. Data were summarized using descriptive statistics.
Results: APPs (n=87) provided data for 914 patients (mean age±[SD]=41.8±18.4 years; 55% female). Of these, 446 patients were on systemics±topicals and 304 were on topicals only. Mean±(SD) body surface area involvement was 13.9±17.0 and 12.3±13.6 in systemics±topicals and topicals-only groups, respectively. The proportion of patients with moderate-to-severe AD was 48.0 percent and 56.3 percent in systemics±topicals and topicals-only groups, respectively. APPs reported that 27 percent of patients on systemics±topicals and 38 percent on topicals only experienced issues with current treatment, with the most frequent issues being loss of response over time and failure to resolve all symptoms (≥25% in each group). Additional issues included lack of adherence (systemics±topicals [16%], topicals-only [23%]), AD worsened (16%, 21%), inconvenient/burdensome therapy (5%, 16%), and struggles with mode of administration (5%, 14%), respectively. Full adherence to systemic treatments was reported by APPs among 49 percent of patients in systemics±topicals group. Full adherence to topicals was reported among 58 percent of patients in systemics±topicals and 37 percent of patients in topicals-only group, respectively. A self-completion survey was filled out by 116 patients in systemics±topicals and 55 in topicals-only groups. The mean±(SD) ADAQ scores were 0.5±0.6 and 0.8±0.7 for systemics±topicals and topicals-only groups, respectively. The proportion of patients extremely/very satisfied with the current prescribed treatment(s) was 63.5 percent and 41.8 percent in systemics±topicals and topicals-only groups, respectively.
Conclusion: This descriptive study suggests that systemics±topicals therapy could provide higher patient satisfaction, better treatment adherence, and less burdensome than topicals-only therapy. Additionally, systemics±topicals therapy resulted in low rates of therapy issues related to mode of administration. Despite these benefits, newer advanced systemic therapies with strong efficacy and flexible dosing may further improve patient adherence and reduce treatment challenges.
Melanoma
Enabling access to prognostic gene expression profile (GEP) testing for invasive melanoma by leveraging RNA-based testing in the diagnostic workflow
Presenters: Brooke H. Russell,1 Mark Sommer,1 Sherri Borman,1 Jeffrey K Wilkinson,1 Kristen M. Oelschlager,1 Trisha M. Poteet,1 Brian J. Martin,1 and Matthew S. Goldberg,1,2
Affiliations: 1Castle Biosciences, Inc., Friendswood, TX; 2Icahn School of Medicine at Mount Sinai, New York, NY
Introduction: 31-GEP prognostic testing is an important tool for patients diagnosed with invasive melanoma and stratifies patients into groups at low, intermediate, or high risk of recurrence, metastasis, or death. The pathway to a melanoma diagnosis is not always straightforward and often dermatopathologists utilize molecular testing to assist in the accurate classification of ambiguous lesions, which utilize varied tissue amounts. Separately, the 23-GEP test is an objective molecular ancillary diagnostic test, which uses RNA extracted from nine unstained slides. Both diagnostic (23-GEP) and prognostic (31-GEP) tests are offered from the same laboratory and can utilize the same RNA. Here, 23-GEP clinical order trends are described March through July 2023.
Methods: 23-GEP tissue was primarily obtained from shave biopsies (88.6%, where biopsy type was specified). Overall, 57.5 percent of samples were female, and median patient age was 49.5 years.
Results: The test result distribution was 61.8 percent benign, 20.3 percent malignant, 13.7 percent intermediate, and 4.2 percent technical fail. Median turnaround time (TAT) (calculated as receipt of tissue until report date and inclusive of weekends and holidays) of 23-GEP was 4 days (interquartile range=2, 5). If a 23-GEP-tested clinical order subsequently receives an invasive melanoma diagnosis, 31-GEP can be utilized efficiently without additional tissue and RNA extraction time.
Conclusion: In conclusion, when the 23-GEP ancillary test is utilized to achieve a confident diagnosis in an otherwise ambiguous neoplasm, rapid access to 31-GEP prognostication without the need for additional tissue can be achieved.
Miscellaneous
Efficacy and safety of apremilast for the treatment of Japanese patients with palmoplantar pustulosis: 52-week results from a Phase 3, randomized, placebo controlled study
Presenters: Yukari Okubo,1 Masamoto Murakami,2 Satomi Kobayashi,3 Akimichi Morita,4 Shinichi Imafuku,5 Yayoi Tada,6 Masatoshi Abe,7 Bruce Strober,8 Melinda Gooderham,9 Masafumi Yaguchi,10 Takeshi Kimura,10 Junichiro Shimauchi,10 Ryuichi Ogawa,10 Wendy Zhang,11 Hamid Amouzadeh,11 Tadashi Terui,12
Affiliations: 1Tokyo Medical University, Tokyo, Japan; 2Miyazaki University, Miyazaki, Japan; 3Seibo International Catholic Hospital, Tokyo, Japan; 4Nagoya City University, Nagoya City, Japan; 5Fukuoka University, Fukuoka, Japan; 6Teikyo University, Tokyo, Japan; 7Sapporo Skin Clinic, Sapporo, Japan; 8Central Connecticut Dermatology Research, Cromwell, CT, USA; 9SKiN Centre for Dermatology, Ontario, Canada; 10Amgen K.K., Tokyo Japan; 11Amgen Inc., Thousand Oaks, CA, USA; 12Nihon University School of Medicine, Tokyo, Japan
Introduction: Palmoplantar pustulosis (PPP) is a difficult-to-treat, chronic dermatitis with limited treatment options. A Phase 3 trial of apremilast 30mg twice daily in Japanese patients with moderate-to-severe PPP showed superior efficacy compared with placebo at Week (W)16. The objective of this analysis was to report apremilast efficacy and safety over 52 weeks.
Methods: This was a randomized, placebo-controlled, double-blind, confirmatory Phase 3 study. Adults with PPP Area and Severity Index (PPPASI) total score of at least 12, PPPASI pustules/vesicles severity score of at least 2, and inadequate response to topicals were randomized (1:1) to apremilast or placebo for 16 weeks. After W16, patients continued on apremilast (apremilast/apremilast) or switched from placebo to apremilast (placebo/apremilast) through W52. W52 endpoints included at least a 50-percent improvement in PPPASI total score (PPPASI-50); changes from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI) total score, Patient’s Visual Analog Scale (VAS) assessment for pruritus and pain/discomfort, Dermatology Life Quality Index (DLQI); and treatment-emergent adverse events (TEAEs). Data are reported as observed.
Results: Among 176 patients randomized (apremilast, n=88; placebo, n=88), 164 (93.2%) completed W52 (apremilast/apremilast, n=84 [95.5%]; placebo/apremilast, n=80 [90.9%]). Baseline characteristics were balanced across groups: mean age, 57.0 vs. 56.0 years; PPP duration, 6.7 vs. 6.0 years; PPPASI total score, 22.1 vs. 22.0; PPSI total score, 8.1 vs. 8.0; pruritus VAS, 48.7 vs. 51.2; pain/discomfort VAS, 43.3 vs. 45.8; and DLQI, 5.7 vs. 6.7. Improvements at W16 were maintained or further improved through W52 in the apremilast/apremilast group for PPPASI-50 response (W16: 71.3%, W52: 79.8%) and mean change from baseline in PPPASI total score (W16: −13.1, W52: −14.7), PPSI total score (W16: −3.7, W52: −4.6); pruritus VAS (W16: −18.1, W52: −19.1), pain/discomfort VAS (W16: −19.2, W52: −18.8), and DLQI (W16: −2.3, W52: −2.4). Patients who switched from placebo to apremilast at W16 experienced rapid improvements in clinical efficacy, with similar levels of response as the apremilast/apremilast group by W24; these improvements were maintained through W52. TEAEs were consistent with the known apremilast safety profile.
Conclusion: Improvements in PPP seen with apremilast at W16 were maintained or further improved through W52, including improvements in PPP severity, symptoms (pruritus and pain/discomfort), and patient-reported quality of life. Improvements were also observed when patients transitioned from placebo to apremilast at W16 through W52. No new safety signals were observed.
Psoriasis
Deucravacitinib in plaque psoriasis: 4-year safety and efficacy results from the phase 3 POETYK PSO-1, PSO-2, and LTE trials
Presenters: April W. Armstrong,1 Mark Lebwohl,2 Richard B. Warren,3,4 Howard Sofen,1,5 Akimichi Morita,6 Shinichi Imafuku,7 Mamitaro Ohtsuki,8 Lynda Spelman,9 Thierry Passeron,10 Kim A. Papp,11 Matthew J. Colombo,12 John Vaile,12 Eleni Vritzali,12 Kim Hoyt,12 Carolin Daamen,12 Subhashis Banerjee,12 Bruce Strober,13 Diamant Thaçi,14 Andrew Blauvelt15
Affiliations: 1University of California Los Angeles, Los Angeles, CA, USA; 2Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK; 4NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 5Dermatology Research Associates, Los Angeles, CA, USA; 6Nagoya City University, Nagoya, Japan; 7Fukuoka University Hospital, Fukuoka, Japan; 8Jichi Medical University, Tochigi, Japan; 9Veracity Clinical Research, Brisbane, QLD, Australia; 10Université Côte d’Azur, University Hospital of Nice, Nice, France; 11Alliance Clinical Trials and Probity Medical Research, Waterloo, and the University of Toronto, Toronto, ON, Canada; 12Bristol Myers Squibb, Princeton, NJ, USA; 13Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, CT, USA; 14University of Lübeck, Lübeck, Germany; 15Blauvelt Consulting, Portland, OR, USA
Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the global, 52-week, Phase 3 POETYK PSO-1 and PSO-2 parent trials in moderate-to-severe plaque psoriasis. Upon completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety/efficacy are reported through four years.
Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6mg once daily, or apremilast 30mg twice daily. At Week 52, patients enrolled in the LTE received openlabel deucravacitinib. Safety was evaluated in patients receiving at least one deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials.
Results: 1,519 patients received at least one deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the one-year to four-year cumulative period, respectively, for AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), major adverse cardiovascular events (0.3, 0.3), and venous thromboembolism (0.2, 0.1). Clinical response rates with continuous deucravacitinib (n=513) were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6-78.0]; PASI 90, 49.0% [44.4-53.7]; sPGA 0/1, 55.2% [50.5-59.9]) to Year 4 (PASI 75, 71.7% [67.0-76.3]; PASI 90, 47.5% [42.6-52.4]; sPGA 0/1, 57.2% [52.1-62.2]) by mNRI.
Conclusion: Deucravacitinib demonstrated a safety profile through four years consistent with three years with no emergence of new or long-term safety signals. Efficacy was maintained through four years in patients receiving continuous deucravacitinib from Day 1 in PSO-1/PSO-2.
Funding/financial disclosures: Funding was provided by Bristol Myers Squibb.
Disclosures: AWA: Research investigator, scientific advisor, and/or speaker for AbbVie, Almirall, Arcutis, Aslan, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, EPI Health, Incyte, Janssen, Leo Pharma, Lilly, Mindera Health, Nimbus, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB.
ML: Research funds on behalf of Mount Sinai: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant, Incyte, Janssen, Lilly, Ortho Dermatologics, Regeneron, and UCB; Consultant: Almirall, AltruBio, AnaptysBio, Arcutis, Avotres, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Castle Biosciences, Celltrion, CorEvitas Psoriasis Registry, Dermavant, EPI Health, Evommune, Forte Biosciences, Galderma, Genentech, Incyte, Leo Pharma, Meiji Seika Pharma, Mindera Health, Pfizer, Seanergy, Strata, Trevi, and Verrica.
RBW: Research grants: AbbVie, Almirall, Amgen/Celgene, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen/Celgene, Astellas, Boehringer Ingelheim, DICE Therapeutics, GSK, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, UCB, and Union.
HS: Clinical investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis, and Sun Pharma.
AM: Honorarium as meeting chair/lecturer: AbbVie, Ayumi, Boehringer Ingelheim Japan, Celgene K.K., Eisai, Eli Lilly Japan K.K., Inforward, Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho Co., Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis Pharma K.K., Taiho Pharmaceutical, Torii Pharmaceutical, and Ushio; Funding: AbbVie G.K., Eisai, Eli Lilly Japan K.K., Kyowa Hakko Kirin, Leo Pharma K.K., Maruho, Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Taiho Pharmaceutical, and Torii Pharmaceutical; Consulting fees: AbbVie GK, Boehringer Ingelheim Japan, Bristol Myers Squibb, Celgene K.K., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Kyowa Kirin, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Nippon Kayaku, Novartis Pharma K.K., Pfizer Japan, Sun Pharma, Torii Pharmaceutical, and UCB Japan.
SI: Grants and/or personal fees: AbbVie, Alexion Pharma, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Janssen, GSK, Kaken, Kyowa Kirin, Leo Pharma, Lilly, Maruho, Novartis, Sun Pharma, Taiho Yakuhin, Torii Yakuhin, and UCB.
MO: Honoraria and/or research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Janssen, Kyowa Kirin, Leo Pharma, Lilly, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, and UCB.
LS: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Connect Biopharma, Celgene, Genesis Care, Dermira, Enkang, Equillium, Evelo Biosciences, Genesis Care, Galderma, Genentech, GSK, Hexima, Incyte, InflaRx GmbH, Invion, Janssen, Kiniksa, Kobio Labs, Leo Pharma, LG Chem, Lilly, Lipidio Pharma, Mayne, Medimmune, Merck, Merck-Serono, Novartis, Nektar Therapeutics, Olix, Otsuka, Pfizer, Phosphagenics, Photon MD, Principia, Regeneron, Ribon, Samumed, Sanofi Genzyme, SHR, Sun Pharma, Takeda, UCB, and Zai Lab.
TP: Advisory board and consulting fees: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB.
KAP: Consultant: AbbVie, Acelyrin, Akros, Amgen, Aralez, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Coherus, Dermavant, Dermira, DICE Therapeutics, Dow Pharma, Evelo Biosciences, Forbion, Galderma, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Lilly, Meiji Seika Pharma, Merck, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv Therapeutics, and Xencor; Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Galderma, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Lilly, Merck, Novartis, Pfizer, and Sanofi Genzyme; Clinical research grants: AbbVie, Akros, Amgen, Anacor, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Coherus BioSciences, Dermavant, Dermira, DICE Therapeutics, Dow Pharma, Evelo Biosciences, Galderma, Gilead, GSK, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, and UCB; Honoraria: AbbVie, Acelyrin, Akros, Amgen, Aralez, Bausch Health/Valeant, Boehringer Ingelheim, Celltrion, Coherus BioSciences, Dermavant, DICE Therapeutics, Forbion, Galderma, Janssen, Kyowa Kirin, Leo Pharma, Lilly, Meiji Seika Pharma, Merck, Mitsubishi Pharma, Novartis, Pfizer, Reistone, Sanofi Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv Therapeutics, and Xencor; Scientific officer: Akros, Anacor, Arcutis, DICE Therapeutics, and Kyowa Kirin; Steering committees: AbbVie, Amgen, Bausch Health/Valeant, Boehringer Ingelheim, Janssen, Kyowa Kirin, Lilly, Merck, Novartis, Pfizer, Regeneron, Reistone, and Sanofi Genzyme; Advisory boards: AbbVie, Amgen, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, DICE Therapeutics, Dow Pharma, Galderma, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB.
MJC, JV, EV, and CD: Employees and shareholders: Bristol Myers Squibb.
KH: Consultant: Bristol Myers Squibb via Syneos Health.
SB: Employee at the time of study conduct and shareholder: Bristol Myers Squibb.
BS: Consultant (honoraria): AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, GSK, Immunic Therapeutics, Janssen, Leo Pharma, Lilly, Maruho, Meiji Seika Pharma, Mindera Health, Novartis, Ortho Dermatologics, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, Ventyx Biosciences, and vTv Therapeutics; Speaker: AbbVie, Janssen, Lilly, and Sanofi Genzyme; Co-scientific director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara Therapeutics, CorEvitas Psoriasis Registry, Dermavant, Dermira, and Novartis.
DT: Research support and principal investigator (clinical trials funds to institution): AbbVie, Almirall, Amgen, Biogen Idec, Bristol Myers Squibb , Boehringer Ingelheim, Galderma, GSK, Janssen-Cilag, Leo Pharma, Lilly, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, and UCB; Consultant: AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Leo Pharma, Novartis, Pfizer, and UCB; Lecturer: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, MSD, Novartis, Pfizer, Roche-Posay, Sandoz-Hexal, Sanofi, Target RWE, and UCB; Scientific advisory board: AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Morphosis, MSD, Novartis, Pfizer, Sanofi, and UCB.
AB: Speaker (with honoraria): AbbVie, Bristol Myers Squibb, Lilly, Pfizer, Regeneron, and Sanofi; Scientific adviser (with honoraria): AbbVie, Abcentra, Aclaris, Affibody, Aligos, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Arena, Aslan, Athenex, Bluefin Biomedicine, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, CTI BioPharma, Dermavant, EcoR1, Escient, Evelo Biosciences, Evommune, Forte Biosciences, Galderma, HighlightII Pharma, Incyte, InnoventBio, Janssen, Landos, Leo Pharma, Lilly, Lipidio, Merck, Nektar, Novartis, Pfizer, Rani, Rapt, Regeneron, Sanofi Genzyme, Spherix Global Insights, Sun Pharma, Takeda, TLL Pharmaceutical, TrialSpark, UCB, Union, Ventyx Biosciences, Vibliome, and Xencor; Clinical study investigator (institution has received clinical study funds): AbbVie, Acelyrin, Allakos, Almirall, Alumis, Amgen, Arcutis, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Evelo Biosciences, Evommune, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, UCB, and Ventyx Biosciences.
Deucravacitinib in plaque psoriasis: laboratory parameters through 4 years of treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE trials
Presenters: Neil J. Korman,1 Thierry Passeron,2 Yukari Okubo,3 Jerry Bagel,4 Richard B. Warren,5,6 Lynda Spelman,7 Kevin Winthrop,8 Kim Hoyt,9 Thomas Scharnitz,9 Subhashis Banerjee,9 Diamant Thaçi,10 Mona Shahriari,11 Linda Stein Gold12
Affiliations: 1Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH, USA; 2Université Côte d’Azur, University Hospital of Nice, Nice, France; 3Tokyo Medical University, Tokyo, Japan; 4Psoriasis Treatment Center of New Jersey, East Windsor, NJ, USA; 5Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester, UK; 6NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 7Veracity Clinical Research, Brisbane, QLD, Australia; 8Oregon Health & Science University, Portland, OR, USA; 9Bristol Myers Squibb, Princeton, NJ, USA; 10University of Lübeck, Lübeck, Germany; 11Yale University School of Medicine, New Haven, and Central Connecticut Dermatology, Cromwell, CT, USA; 12Henry Ford Health System, West Bloomfield, MI, USA
Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, Phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through four years of deucravacitinib treatment.
Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed.
Results: A total of 1,519 patients received at least one deucravacitinib dose (total exposure, 4392.8 person-years); 1,203 (79.2%) had at least 52 weeks and 542 (35.7%) had at least 208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, three patients discontinued treatment due to increased CPK, and one patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed.
Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through four years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.
Funding/financial disclosures: Funding was provided by Bristol Myers Squibb and was supported by the NIHR Manchester Biomedical Research Centre.
Disclosures: NJK: Advisory board and consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, Leo Pharma, Lilly, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Galderma, Kyowa Kirin, Leo Pharma, Lilly, Menlo Therapeutics, Principia, Prothena, Rhizen, Syntimmune, Trevi, and XBiotech; Speaker: AbbVie, Janssen, Lilly, Novartis, Regeneron, and Sanofi Genzyme.
TP: Advisory board and consulting fees: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB.
YO: Research grants: AbbVie, Eisai, Maruho, Shiseido, Sun Pharma, and Torii; Honoraria: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, Janssen Pharma, Jimro, Kyowa Kirin, Leo Pharma, Lilly, Maruho, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB; Clinical trials: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Maruho, Pfizer, Sun Pharma, and UCB.
JB: Research funds payable to the Psoriasis Treatment Center of New Jersey: AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, CorEvitas Psoriasis Registry, Dermavant, Dermira/UCB, Glenmark, Janssen Biotech, Kadmon, Leo Pharma, Lilly, Lycera, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sun Pharma, Taro, and Valeant; Consultant: AbbVie, Amgen, Janssen Biotech, Lilly, Novartis, Sun Pharma, and Valeant; Speaker: AbbVie, Celgene, Janssen Biotech, Lilly, and Novartis.
RBW: Research grants: AbbVie, Almirall, Amgen, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; Consulting fees: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, DICE Therapeutics, GSK, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, UCB, and Union Therapeutics.
LS: Consultant, paid investigator, advisory board and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Boehringer Ingelheim, Botanix, Bristol Myers Squibb, Celgene, Connect Biopharma, Dermira, Enkang, Equillium, Evelo Biosciences, Galderma, Genesis Care, Genentech, GSK, Hexima, Incyte, InflaRx GmbH, Invion, Janssen, Kiniksa, Kobio Labs, Leo Pharma, LG Chem, Lilly, Lipidio Pharma, Mayne, Medimmune, Merck, Novartis, Nektar Therapeutics, Olix, Otsuka, Pfizer, Phosphagenics, Photon MD, Principia, Regeneron, Ribon, Samumed, Sanofi Genzyme, SHR Pharmacy, Sun Pharma, Takeda, UCB, and Zai Lab.
KW: Consultant: AbbVie, AstraZeneca, Bristol Myers Squibb, Galapagos, Gilead, GSK, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB; Research support: Bristol Myers Squibb and Pfizer.
KH: Consultant: Bristol Myers Squibb via Syneos Health.
TS and SB: Employees at the time of study conduct and shareholders: Bristol Myers Squibb.
DT: Research support and principal investigator (clinical trial funds to institution): AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi, and UCB; Consultant: AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Leo Pharma, Novartis, Pfizer, and UCB; Lecturer: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Roche-Posay, Sanofi, Target RWE, and UCB; Scientific advisory board: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, and UCB.
MS: Consultant (honoraria): AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Dermavant, Galderma, Janssen, Leo Pharma, Lilly, Novartis, Ortho Dermatologics, Sanofi Genzyme, Regeneron, and UCB; Speaker: AbbVie, Arcutis, Bristol Myers Squibb, Dermavant, Janssen, Leo Pharma, Lilly, Pfizer, and UCB; Investigator: AbbVie, Cara Therapeutics, CorEvitas Psoriasis and Atopic Dermatitis Registry, Dermavant, Dermira, Mindera Health, Novartis, and Union Therapeutics.
LSG: Consultant, advisory board member, and/or speaker: AbbVie, Amgen, Arcutis, Aslan, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Dermira, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB.
Expected spesolimab plasma exposure following intravenous and subcutaneous dosing in patients with generalized pustular psoriasis
Presenters: Jason E. Hawkes,1 Jason R. Guercio,2 Sree Kurup,2 Xiujiang Li,2 Mark G. Lebwohl,3
Affiliations: 1Oregon Medical Research Center, Portland, OR, USA; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 3The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Introduction: Generalized pustular psoriasis (GPP) is a chronic, potentially life-threatening inflammatory skin disease characterized by widespread flares of sterile pustules. Spesolimab is a first-in-class anti-interleukin-36 receptor monoclonal antibody approved in the US in adults and pediatric patients 12 years of age and older and weighing at least 40kg, as a subcutaneous (SC) dosage for treatment of GPP when not experiencing a flare, and as an intravenous (IV) dosage for treatment of GPP flare. The aim of this study was to simulate the plasma pharmacokinetics (PK) of IV versus SC doses of spesolimab to compare drug exposure profiles and support dosing strategies in patients with GPP.
Methods: A population PK model was developed using individual-level PK, anti-drug antibody, and covariate data from 18 studies in which subjects were treated with IV or SC spesolimab.1 The resulting PK model was used to simulate concentration-time profiles following varying doses of IV and SC spesolimab. Peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), and area under the curve (AUC) were summarized for each dose regimen.
Results: Simulated spesolimab exposures demonstrated that the Cmax and AUC of the single dose 900mg IV infusion consistently exceeded that of various single doses of SC spesolimab tested. A SC dose greater than two-fold higher would be required to attain a Cmax comparable to that of spesolimab 900mg IV. The difference in exposure between the two administration routes was most pronounced in the first two weeks after administration. Slow absorption is expected with SC injection, with Tmax attained at later time points after SC dosing compared to immediately following the 90-minute infusion for IV dosing. Results were the same when simulating a two-dose regimen administered one week apart.
Conclusion: PK simulations suggest that treatment with IV and SC spesolimab can result in differences in drug exposure in clinical practice. The immediate and high exposure of IV spesolimab compared with the lower exposure of SC spesolimab are supportive of IV dosing with spesolimab in acute GPP flare treatment versus SC dosing for GPP treatment when not experiencing flares.
Effectiveness of biologics in clinical practice: interim Month 24 results from the International Observational Psoriasis Study of Health Outcomes (PSoHO)
Presenters: April W. Armstrong,1 Julia-Tatjana Maul,2,3 Antonio Costanzo,4 Saxon D. Smith,5 Bruce Konicek,6 Meghan Feely,6 Natalie Haustrup,6 Anastasia Lampropoulou,6 Alan Brnabic,6 Andreas Pinter7
Affiliations: 1Department of Dermatology, University of Southern California, Los Angeles, California, USA; 2Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland; 3Faculty of Medicine, University of of Zürich, Zürich, Switzerland; 4Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; 5ANU Medical School, ANU College of Health and Medicine, The Australian National University, Canberra, Australia; 6Eli Lilly and Company, Indianapolis, USA; 7University Hospital Frankfurt, Frankfurt am Main, Germany
Introduction: Evaluate the long-term dynamics of treatment response rates through Month 24 for patients with moderate-to-severe psoriasis (PsO) treated with biologics in a real-world setting.
Methods: PSoHO is an ongoing international, prospective, observational study comparing the effectiveness of anti-interleukin (IL)-17A biologics to other approved biologics (IL-17RA, TNFα, IL-12/23 and IL-23) for the treatment of PsO. Building on Week (W)12, Month (M)6 and M12 data, this preliminary interim analysis evaluates the proportion of patients receiving EMA-approved on-label dosing who achieved PASI100 at M18 and M24. Outcomes were descriptively evaluated for the anti-IL-17A and other biologics cohorts, and selected individual treatments. Results are presented as observed and using nonresponder imputation (NRI) for binary outcomes.
Results: From the 1,678 patients who received EMA-approved on-label dosing, 1,185 patients completed the M18 visit, and 768 patients completed the M24 visit. At all time points through M24, the anti-IL-17A cohort had numerically higher PASI100 response rates than the other biologics cohort. Using NRI, the proportion (95% confidence intervals) of patients who achieved PASI100 in the anti-IL-17A and other biologics cohorts was 39.2% (35.5, 42.9) and 35.1 percent (32.2, 38.0) at M18, and 29.2 percent (25.8, 32.7) and 21.1 percent (18.6, 23.6) at M24, respectively. This pattern, although with higher response rates, was also reported in the as-observed population.
Conclusion: Building on previous W12, M6 and M12 PSoHO data, this interim analysis demonstrates the continued high-level effectiveness and durability of response of anti-IL-17A biologics through M24 and the varying effectiveness dynamics of biologics, including ixekizumab, in a real-world setting.
Funding/financial disclosures: Funding was provided by Eli Lilly and Company.
Effectiveness of ixekizumab on skin, itch and quality of life through 24 weeks from the second interim analysis of a US observational psoriasis study
Presenters: David Fivenson,1 Brandon Kirsch,2 Bartley Joseph Gill,3 William Malatestinic,4 Mwangi Murage,4 Ali Sheikhi Mehrabadi,4 Edward Herman,5
Affiliations: 1Fivenson Dermatology, Ann Arbor, USA; 2Kirsch Dermatology, Naples, USA; 3Complete Dermatology, Houston, USA; 4Eli Lilly and Company, Indianapolis, USA; 5South Shore Dermatology Physicians, North Easton, USA.
Objective: To gain more real-world (RW) insights, we provide descriptive data on a second interim analysis from the prospective Psoriasis in Special Areas (PSoSA) study.
Methods: PSoSA is a US-based, multicenter, single-arm, prospective, observational study enrolling adult patients with a confirmed diagnosis of moderate-to-severe psoriasis (PsO) and nail involvement, with or without scalp involvement, whose HCP/physician has prescribed IXE for the first time. For the second interim analysis of the PSoSA study, we assess the effectiveness of IXE treatment at Weeks 4, 12 and 24, through evaluation of the Psoriasis Area and Severity Index (PASI), Itch Numeric Rating Scale (NRS) and Dermatology Life Quality Index (DLQI) and present a descriptive analysis of results obtained. Continuous and categorical variables are reported.
Results: During second interim analysis (December 2023), 187 patients were assessed. Use of at least one concomitant PsO therapy other than IXE was reported by 19.3 percent of patients at baseline (0.5% phototherapy and 18.7% topical). Biologic systemic agents were discontinued by 67.3 percent of patients within 12 months prior to enrollment. Week 4 demonstrated improvements in PsO, itch and quality of life in patients treated with IXE and continued up to Week 24. Specifically, mean (±SD) baseline PASI score (10.4±11.69) improved by 6.3 points by Week 4 (4.1±5.04), an additional 2.3 points by Week 12 (1.8±3.32) and a further 0.8 by Week 24 (1.0±1.87). PASI90 was achieved by 18.8 percent of patients by Week 4, by Week 12 this increased to 54.0 percent of patients and by Week 24, to 69.6 percent of patients. PASI100 was achieved by 10.9 percent of patients by Week 4, 27.4 percent of patients by Week 12 and 43.5 percent of patients by Week 24. An Itch NRS score of 0 (no itch) was reported by 17.8 percent of patients by Week 4, 29.7 percent of patients by Week 12 and 41.8 percent of patients by Week 24. At Week 4, 41.9 percent of patients reported at least a four-point improvement from their baseline recorded Itch NRS score of at least 4. By Week 12, this increased to 45.0 percent of patients and by Week 24, 57.6 percent of patients. DLQI (0,1) was reported by 22.2 percent of patients by Week 4, 42.9 percent of patients by Week 12 and 61.2 percent of patients by Week 24.
Conclusion: This second interim analysis of the PSoSA study demonstrates improvement in PASI, itch and DLQI scores as early as Week 4 and up to week 24 in patients initiating IXE treatment.
Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 52-week results from the SPROUT randomized controlled trial
Presenters: Loretta Fiorillo,1 Emily Becker,2 Susana Armesto,3 Amy S. Paller4
Apostolos Kontzias,5 Rajneet K. Oberoi,5 Yuri Klyachkin,5 Hamid Amouzadeh,5 Zuoshun Zhang,5 Lisa Arkin6
Affiliations: 1Stollery Children’s Hospital University of Alberta, Edmonton, Alberta, Canada; 2Driscoll Children’s Hospital, Corpus Christi, TX, USA; 3Hospital Universitario Marques de Valdecilla, Santander, Spain; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5Amgen Inc., Thousand Oaks, CA, USA; 6University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Introduction: Systemic treatment options are limited for pediatric patients with moderate-to-severe plaque psoriasis (PsO). Apremilast, an oral phosphodiesterase-4 inhibitor approved for adult PsO, has recently been approved as the only oral treatment for pediatric moderate-to-severe PsO. The SPROUT trial evaluated the efficacy and safety of apremilast over 52 weeks in pediatric patients with moderate-to-severe PsO.
Methods: SPROUT (NCT03701763) was a Phase 3, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6 to 17 years with moderate-to-severe PsO (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, and static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age and randomized (2:1) to apremilast (weight-based: 20mg for ≥20 to <50kg or 30mg for ≥50kg, twice-a-day) or placebo for 16 weeks, after which all patients continued to receive apremilast (apremilast/apremilast) or switched from placebo to apremilast (placebo/apremilast) through Week 52. At Week 16, primary (sPGA response: 33.1% vs 11.5%) and major secondary (PASI-75: 45.4% vs 16.1%) endpoints were met (p<0.0001; Fiorillo et al, SKIN, 2023; 7[2]:s109). Here, we report 52-week sPGA, PASI-75, and safety results.
Results: Of 245 randomized patients (apremilast: 163; placebo: 82), 221 (apremilast: 149 [91.4%]; placebo: 72 [87.8%]) completed the placebo-controlled period and 186 (apremilast/apremilast: 125 [76.7%]; placebo/apremilast: 61 [74.4%]) completed the 36-week extension. At Week 52, 56.3 percent of apremilast/apremilast patients achieved sPGA response and 71.4 percent achieved PASI-75, demonstrating continued improvement from Weeks 16 through 52. Placebo/apremilast patients also achieved sPGA response (52.5%) and PASI-75 (75.4%) at Week 52. The safety profile was consistent with prior apremilast studies in adults. Most common treatment-emergent adverse events were gastrointestinal in nature and transient, resolving within 30 days. Apremilast pharmacokinetic profiles were similar regardless of treatment group or weight-based dose.
Conclusion: Improvements in psoriasis severity and skin involvement were observed in pediatric patients treated with apremilast for 52 weeks. Adverse events reflected the known apremilast safety profile.
Four-weekly dosing intervals with subcutaneous spesolimab appear to be required for optimal prevention of generalized pustular psoriasis flares: data from the Effisayil 2 and Effisayil ON trials
Presenters: Diamant Thaçi,1 Akimichi Morita,2 Bruce E. Strober,3 Tiago Torres,4 Andreas Pinter,5 Angelo V. Marzano,6 James G. Krueger,7 Ming Tang,8 Patrick Hofmann,9 Christian Thoma,9 Mark G. Lebwohl10
Affiliations: 1Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; 2Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 3Department of Dermatology, Yale University School of Medicine, New Haven, and Central Connecticut Dermatology Research, Cromwell, CT, USA; 4Department of Dermatology, Centro Hospitalar Universitàrio de Santo António, University of Porto, Porto, Portugal; 5Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt am Main, Frankfurt am Main, Germany; 6Dermatology Unit, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 7Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA; 8Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai, China; 9Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 10The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Introduction: Generalized pustular psoriasis (GPP) is a rare chronic skin disease characterized by recurrent, acute, and often life-threatening flares of widespread neutrophilic sterile pustules and systemic inflammation. Spesolimab, an anti-interleukin-36 receptor antibody, is approved in the US in adults and pediatric patients 12 years of age and older and weighing at least 40kg, as a subcutaneous (SC) dosage for treatment of GPP when not experiencing a flare, and as an intravenous (IV) dosage for treatment of GPP flare. In Effisayil 2, a randomized, placebo-controlled trial (NCT04399837), SC spesolimab was superior to placebo and well tolerated for flare prevention when administered as a 600mg SC loading dose followed by 300mg every four weeks (q4w) over 48 weeks. In Effisayil 2, 3/30 (10.0%) patients receiving SC spesolimab 300mg q4w had flares, and there were no flares after Week 4 until the end of the study.
Methods: We assessed the effect on flare recurrence of a longer (q12w) interval between SC spesolimab doses in Effisayil 2 and Effisayil ON (NCT03886246), an ongoing open-label extension trial. Flares were defined as at least a two-point increase in GPP Physician Global Assessment total score with pustulation subscore of at least 2, or IV spesolimab or standard of care treatment due to GPP worsening.
Results: In Effisayil 2, 9/31 (29.0%) patients who received SC spesolimab 300mg q12w had a flare; of those, 7/9 (77.8%) experienced a flare before their second SC dose (Week 12), and 5/7 (71.4%) flares occurred during Weeks 4 to 12, indicating the need for q4w dosing. In Effisayil ON, 36/108 (33.3%) patients who started q12w dosing were either escalated to a q4w regimen (n=24) or experienced a flare (n=12).
Conclusion: These observations suggest that SC spesolimab 300mg q4w is the optimal dosing regimen for prevention of GPP flares.
Patient-reported outcomes with roflumilast foam 0.3% in patients with scalp and body psoriasis in the Phase 3 ARRECTOR trial
Presenters: Melinda J. Gooderham,1 Jerry Bagel,2 Seth B. Forman,3 Leon H. Kircik,4 Marni Wiseman,5 Benjamin Lockshin,6 Jennifer Soung,7 David Krupa,8 Saori Kato,8 David R. Berk,8 David H. Chu8
Affiliations: 1SKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, ON, Canada; 2Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA; 3ForCare Medical Center, Tampa, FL, USA; 4Icahn School of Medicine at Mount Sinai, New York, NY; Indiana Medical Center, Indianapolis, Physicians Skin Care, PLLC and Skin Sciences, PLLC, Louisville, KY, USA; 5SKiNWISE Dermatology, Probity Medical Research and University of Manitoba, Winnipeg, MB, Canada; 6DermAssociates, LLC, Rockville, MD, USA; 7Southern California Dermatology, Santa Ana, CA, USA; 8Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA
Introduction: Patients with scalp or body psoriasis consider itch the most burdensome symptom. Roflumilast foam 0.3% is a novel, once-daily formulation of a highly potent phosphodiesterase 4 inhibitor under investigation for treatment of scalp and body psoriasis.
Methods: This Phase 3 trial (ARRECTOR, NCT05028582) was conducted in patients aged at least 12 years with scalp and body psoriasis, minimum Scalp-Investigator Global Assessment (S-IGA) of Moderate, minimum Body-IGA (B-IGA) of Mild, and overall body surface area affected by psoriasis 25 percent or less. Patients were randomized 2:1 to once-daily roflumilast foam 0.3% or vehicle for eight weeks. Primary results were reported previously. Patient-reported outcomes (PROs) included the Psoriasis Symptom Diary (PSD; ≥18 years only), Scalpdex, Dermatology Life Quality Index (DLQI; >17 years only), Scalp Itch-Numeric Rating Scale (SI-NRS), and Worst Itch-Numeric Rating Scale (WI-NRS).
Results: Overall, 281 patients received roflumilast foam and 151 received vehicle. In patients with SI-NRS and WI-NRS≥2 at baseline, a greater proportions of patients in the roflumilast group than the vehicle group achieved scores of 0 or 1 at Week 8 (SI-NRS: 52.3% vs 24.1%; p<0.0001; WI-NRS: 55.4% vs 19.8%; p<0.0001). Similar improvements were reflected in other PROs at Week 8, with a significantly greater proportion of patients treated with roflumilast versus vehicle achieving a PSD total score of 0 (19.6% vs 7.1%; p=0.0012), and significantly greater improvements in least-squares mean changes from baseline in PSD items related to itching/pain/scaling (– 10.9 vs – 5.8; p<0.0001), Scalpdex score (– 23.4 vs – 12.8; p<0.0001), and DLQI (– 4.4 vs – 2.4; p<0.0001).
Conclusion: Roflumilast foam 0.3% improved quality of life associated with scalp and body psoriasis itching, pain, and scaling.
Funding/financial disclosures: Funding was provided by Arcutis Biotherapeutics, Inc.