Scholarly Activity

Purpose: Topical clindamycin, a lincosamide antibiotic, is commonly combined with benzoyl peroxide or a retinoid for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding gastrointestinal (GI) adverse events (AEs), real-world incidence of GI AEs with topical clindamycin is unknown. This review provides background information and an overview of safety data of topical clindamycin for treating AV.

Materials and Methods: Available safety data from published literature, previously unpublished worldwide pharmacovigilance data, and two retrospective cohort studies were reviewed.

Results and Conclusions: According to pharmacovigilance data, the rate of GI adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). Results from two retrospective medical record studies of patients with AV indicated that physicians prescribe topical clindamycin equally to patients with or without inflammatory bowel disease history, and that rates of pseudomembranous colitis in these patients were low. In 8 published pivotal clinical trials of topical clindamycin for AV, GI AEs were reported in 1.4% of participants. Limitations include under/inaccurate reporting of AEs or prescription data and limited generalizability. This review of published case reports, worldwide pharmacovigilance data, retrospective US prescription data, and clinical trials safety data demonstrates that the incidence of colitis in patients exposed to topical clindamycin is extremely low.

BACKGROUND: Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo.

OBJECTIVES: We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment.

METHODS: Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep).

RESULTS: In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders.

CONCLUSIONS: Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD.

UNLABELLED: ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Purpose: Ruxolitinib (selective Janus kinase [JAK] 1 and JAK2 inhibitor) cream demonstrated efficacy and safety in patients with atopic dermatitis (AD) in the phase 3 TRuE-AD studies. In TRuE-AD1/TRuE-AD2 (NCT03745638/NCT03745651), adults and adolescents with mild to moderate AD were randomized to apply twice-daily ruxolitinib cream or vehicle for eight weeks. Here, we evaluated the efficacy and tolerability of ruxolitinib cream by anatomic region, focusing on head/neck (HN) lesions that are typically difficult to manage and disproportionately affect quality of life (QoL).Materials and methods: Eczema Area and Severity Index (EASI) responses in anatomic regions were evaluated in the pooled population (N = 1208) and among patients with baseline HN involvement (n = 663). Itch, Investigator's Global Assessment (IGA), QoL, and application site tolerability were also assessed.

Results: By Week 2 (earliest assessment), ruxolitinib cream application resulted in significant improvements across all EASI anatomic region subscores and AD signs versus vehicle, with further improvements through Week 8. Significantly more patients with HN involvement who applied ruxolitinib cream versus vehicle achieved clinically meaningful improvements in itch, IGA, and QoL. Application site reactions with ruxolitinib cream were infrequent (<3%), including in patients with HN involvement.Conclusions: These results support the use of ruxolitinib cream for AD treatment across all anatomic regions, including HN.

BACKGROUND: The decision to initiate advanced systemics in patients with atopic dermatitis (AD) is complex.

OBJECTIVES: To explore disease burden and clinical characteristics of patients with moderate-to-severe AD and identify characteristics associated with initiating new systemics.

METHODS: Data from prospective, longitudinal, non-interventional CorEvitas AD Registry were evaluated. Differences in demographic and clinical characteristics, comorbidities, disease severity (vIGA-AD(™); body surface area (BSA); Eczema Area and Severity Index (EASI); SCORing AD [SCORAD]), and patient-reported outcomes (PROs) were assessed between systemic and non-systemic therapy groups.

RESULTS: Of 883 patients, 673 were newly prescribed systemics and 210 were not. Non-systemic therapy group had higher than expected rates of severe disease at enrollment based on vIGA-AD = 4 (39%), mean BSA involvement (31%), and mean EASI (19). PROs for non-systemic therapy group indicated elevated burden from AD on quality of life and poor disease control. SCORAD, peak pruritus in the past 24 h, history of biologics, and facial pallor, were significantly associated with initiation of systemics at enrollment.

CONCLUSION: While disease burden likely influences the initiation of systemic therapy, many patients with significant burden are not treated with systemics for unclear reasons. Further research is needed to identify other factors, beyond disease severity, that influence this decision.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results.

OBJECTIVES: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids.

METHODS: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale.

RESULTS: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection.

CONCLUSIONS: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved.

BACKGROUND: As exposure to UV radiation is the primary modifiable environmental risk factor associated with skin cancer, it remains the principal focus of most prevention strategies. Numerous sun protection campaigns have been implemented worldwide; however, their impact on the actual incidence and mortality rates of skin cancer seems to be limited. To create successful skin cancer prevention campaigns, it is important to have a comprehensive understanding of individuals' attitudes and behaviours regarding sun protection. The aim of the current study was to determine and report on the prevalence of self-reported attitudes, knowledge and behaviours regarding two of the major sun protection recommendations-avoidance of sun exposure and use of sunscreens-in an international representative sample across five continents.

METHODS: This cross-sectional study was conducted in 20 countries using a web-based online survey.

FINDINGS: A total of 50,552 individuals, comprising 25,388 men (50.22%) and 25,164 women (49.78%), participated in the survey. Among them, 83.2% reported having been voluntarily exposed to the sun (for sun-basking reasons) at least once in the last 12 months, and 47.96% acknowledged being exposed to the sun between the hours of 10 AM and 4 PM. The primary reason for non-adherence was that these hours were the most convenient times (32.28%). Only 24.05% reported applying sunscreen every 2 h when outdoors. Forgetfulness was the primary reason as provided by 27.79% of participants. Males and older age groups were less likely to adopt sun-protective behaviours around the world. Forgetfulness and the challenges posed by time constraints seem to be the biggest barriers to proper adherence.

INTERPRETATION: These findings should prompt the collaboration with health authorities and the manufacturers to enhance adherence by setting reasonable sunscreen prices and creating formulations that make their application less burdensome.

IMPORTANCE: Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin.

OBJECTIVE: To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis.

DESIGN, SETTING, AND PARTICIPANTS: The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy.

INTERVENTIONS: Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period.

MAIN OUTCOMES AND MEASURES: The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12.

RESULTS: Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03726489.

Background Eight-week safety and tolerability, efficacy, and limited systemic absorption of ruxolitinib cream 1.5% in an open-label, single-arm, maximum-use trial (MUsT) of children with moderate to severe atopic dermatitis (AD; NCT05034822) were previously described. This is the first report of longer-term data from the same study. Objectives Data on tolerability, safety, systemic exposure, and clinical and patient-reported outcomes are presented from the entire 52-week treatment period to assess whether clinical benefits and tolerability observed through Week 8 are sustained during the as-needed treatment long-term safety period through Week 52. Methods In this open-label, single-arm MUsT, patients 2-11 years old with AD ≥3 months, ≥35% affected body surface area (BSA), and Investigator's Global Assessment (IGA) ≥3 applied twice-daily ruxolitinib cream 1.5% for 4 weeks to baseline lesions, then as-needed to active lesions for 4 weeks; patients could continue into the as-needed 44-week long-term safety period. Results This MUsT included 29 patients with moderate to severe AD. Treatment-emergent adverse events through Week 52 occurred in 31.0% of patients. One patient (3.4%) had 2 treatment-related application site reactions (paresthesia and folliculitis); no adverse events resulted in treatment interruption/discontinuation; none were serious or suggested systemic Janus kinase (JAK) inhibition. Through the 4-week continuous-use twice-daily treatment period, the mean (SD) application quantity was 8.5 (6.29) g/day, which was associated with a mean steady-state ruxolitinib plasma concentration of 98.2 nM, well below half-maximal concentration of JAK-mediated myelosuppression in adults (281 nM). From Week 8 to Week 52 (as-needed use), mean (SD) application quantity was 3.2 (2.79) g/day, consistent with lower, as-needed use in this long-term safety period. At Weeks 4 and 52 (assessed in n=26 and n=13 patients, respectively), 53.8%/53.8% achieved IGA-Treatment Success (IGA 0/1 with ≥2-grade improvement from baseline). Mean BSA decreased from 58.0% (range, 35.0%-92.0%) at baseline (n=29) to 11.4% at Week 4 and continued to decrease to 2.2% through Week 52 (n=26 and n=14, respectively). Patient-reported outcomes, such as the Patient-Oriented Eczema Measure, Children's Dermatology Life Quality Index, and Infants' Dermatitis Quality of Life Index, were collected through Week 52. Conclusions Ruxolitinib cream 1.5% demonstrated consistently good tolerability and safety over 52 weeks in children aged 2 to 11 years with extensive moderate to severe AD. Rapid lesion clearance over 4 weeks with twice-daily therapy, which was sustained with longer-term as-needed use associated with low quantities of ruxolitinib cream being applied, may address application burden concerns.

Introduction/Background Atopic dermatitis (AD) is a chronic, inflammatory skin disease with onset usually occurring in childhood. Topical therapy is the mainstay of AD treatment and is typically used prior to systemic therapy in patients with moderate disease. Ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream is approved by the US Food and Drug Administration for patients aged ≥12 years with mild to moderate AD, and has demonstrated efficacy and was well tolerated in children (aged 2-11 y) with AD in TRuE-AD3 (NCT04921969), a phase 3, double-blind, randomized, vehicle-controlled study. Objectives Here we investigated the effects of ruxolitinib cream in a subset of patients from TRuE-AD3 with moderate and/or more extensive disease at baseline. Methods TRuE-AD3 included children aged 2-11 years with AD for ≥3 months, an Investigator's Global Assessment (IGA) score of 2 or 3, and an affected body surface area (BSA) of 3%-20%. Patients were randomized 2:2:1 to apply 1.5% ruxolitinib cream, 0.75% ruxolitinib cream, or vehicle cream twice daily for 8 weeks. Rescue treatment was not permitted. Patients from TRuE-AD3 with moderate and/or more extensive disease at baseline (defined as an IGA score of 3, ≥10% affected BSA, or a combined IGA score of 3 and ≥10% BSA) were included in this analysis. Efficacy was assessed as the proportion of patients in each treatment group who achieved IGA treatment success (IGA-TS; a score of 0 or 1 with a ≥2-grade improvement from baseline), ≥75% improvement from baseline in the Eczema Area and Severity Index (EASI75), and ≥90% improvement from baseline in the Eczema Area and Severity Index (EASI-90) at Weeks 2, 4, and 8. Statistical significance was assessed at Week 8 using exact logistic regression. Patients with missing post-baseline data were imputed as nonresponders. Results Patients in TRuE-AD3 (N=330) had a median (range) age of 6 (2-11) years, 54.2% were girls, and 54.5% were White. The mean (SD) BSA was 10.5% (5.4%), the mean (SD) EASI was 8.6 (5.4), and 252 patients (76.4%) had a baseline IGA of 3. Among patients with an IGA of 3 at baseline, more patients who applied 1.5% ruxolitinib cream or 0.75% ruxolitinib cream versus vehicle achieved IGA-TS (40.0% and 29.1%, respectively, vs 6.1%), EASI-75 (43.0% and 38.8% vs 8.2%), and EASI-90 (17.0% and 21.4% vs 0%) at Week 2. Improvements were also observed at Week 8 (IGA-TS, 59.0% [P<0.0001] and 37.9% [P=0.004] vs 14.3%; EASI-75, 64.0% [P<0.0001] and 48.5% [P<0.0001] vs 14.3%; EASI90, 40.0% [P<0.0001] and 33.0% [P=0.001] vs 8.2%), with 1.5% ruxolitinib cream consistently resulting in numerically better improvements than 0.75% ruxolitinib cream. Similar improvements were observed with ruxolitinib cream versus vehicle among patients with ≥10% affected BSA at baseline and a combined baseline IGA of 3 and ≥10% BSA. Both strengths of ruxolitinib cream were well tolerated among patients with an IGA of 3 at baseline; no serious treatment-emergent adverse events (TEAEs) were reported. Conclusions Children with moderate and/or more extensive AD in this study had substantially higher rates of clinical responses with ruxolitinib cream monotherapy versus vehicle as early as Week 2 (first assessment), with further improvement throughout the 8-week treatment period. Ruxolitinib cream was well tolerated with no serious TEAEs.

Introduction/Background Amlitelimab is a fully human, nondepleting anti-OX40 Ligand (OX40L) monoclonal antibody that blocks OX40L-OX40 interactions. In addition to an acceptable safety profile, phase 2a and 2b trials showed the clinical efficacy of amlitelimab in achieving lesional and symptomatic (pruritus) endpoints and demonstrating a continued durable response when patients with moderate-to-severe atopic dermatitis (AD) were withdrawn from amlitelimab during a 28-week period, suggesting the viability of extended interval dosing (every 12 weeks [Q12W]). Objectives Phase 3 clinical trials will determine the efficacy and safety of amlitelimab every four weeks (Q4W) and Q12W dosing in patients with moderate-to-severe AD with various treatment histories. Methods OCEANA phase 3 clinical trials (COAST 1, COAST 2, SHORE, AQUA, and ESTUARY) are multinational, multicenter, randomized, double-blind, parallel group, placebo-controlled trials evaluating efficacy and safety of subcutaneous amlitelimab with two different dosing regimens. Key inclusion criteria for COAST 1/2, SHORE, and AQUA include: adults and adolescents (≥12 years old) having AD ≥1 year with inadequate response to topical treatments (within 6 months before screening) and/or systemic treatment (within 12 months before screening), validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) baseline score of 3 or 4, Eczema Area and Severity Index (EASI) baseline score of ≥16, AD involvement of ≥10% of body surface area at baseline, and weekly average Peak Pruritus Numerical Rating Scale score of ≥4. COAST 1/2 are 24-week monotherapy studies, while SHORE is a 24-week study with background topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). AQUA is a 36-week study with background TCSs and TCIs that exclusively includes participants with an inadequate response to prior treatment with AD biologics or oral Janus kinase inhibitors. Primary endpoints for COAST 1/2, SHORE, and AQUA include vIGA-AD 0/1 and a reduction from baseline of ≥2 points (for US and US reference countries) and vIGA-AD 0/1 and EASI-75 (for Japan, EU, and EU reference countries). Adult patients ≥40 kg will be randomized to amlitelimab 250 mg Q4W + 500 mg loading dose (LD), amlitelimab 250 mg Q12W + 500 mg LD, or placebo; dose will be adjusted for patients <40 kg. Trials have a 2- to 4-week screening period. Primary endpoints will be evaluated at Week 24 for COAST 1/2 and SHORE and at Week 36 for AQUA, with expected enrollment of 420, 420, 496, and 249 patients in each study, respectively. Patients who have completed COAST 1/2 or SHORE can elect to enter the ESTUARY blinded extension study; patients completing AQUA can enter RIVER-AD, an open-label long-term study. Upon entering ESTUARY, clinical responders previously on 250 mg Q4W +LD will be randomized to 250 mg Q4W, 250 mg Q12W, or treatment withdrawal (placebo), while nonresponders will continue on 250 mg Q4W. Clinical responders previously on 250 mg Q12W +LD will be randomized to 250 mg Q12W or treatment withdrawal (placebo), while nonresponders will be randomized to 250 mg Q12W or 250 mg Q4W. Clinical responders previously on placebo will continue placebo, while nonresponders on placebo will receive amlitelimab 250 mg Q4W +LD. Participants not entering the ESTUARY or RIVER-AD trials will be included in a 16-week safety follow-up. ESTUARY and RIVER-AD will evaluate long-term safety and efficacy. Biopsies and blood samples will be collected at various timepoints in the OCEANA phase 3 trials. Results Enrollment for the OCEANA phase 3 trials began Q4 2023. COAST 1/2, SHORE, and AQUA trials are expected to be completed in 2026. Conclusions Results of the clinical trials should provide further evidence demonstrating the efficacy and safety of amlitelimab in treating moderate-to-severe AD using two different dosing regimens, including an extended dosing regimen, in patients with various treatment histories.

Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, immune-mediated inflammatory disease associated with burdensome symptoms including itch, skin pain, sleep disruption, as well as reduced quality of life (QoL).1 It is therefore important to consider signs, symptoms, and QoL impairments when evaluating long-term benefits of AD treatments. Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe AD.2 Objective To evaluate the effects of upadacitinib monotherapy on skin and patient-reported outcomes (PROs) in patients with moderate-to-severe AD over 140 weeks. Methods Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) were replicate, multicenter, phase 3 studies evaluating once-daily oral upadacitinib monotherapy for adolescents (aged 12-17 years) and adults (aged ≥ 18 years) with moderate-to-severe AD.3,4 At baseline, patients were randomized 1:1:1 to upadacitinib 15 mg, upadacitinib 30 mg, or placebo. In this analysis, data for patients who were randomized to upadacitinib 15 mg or upadacitinib 30 mg at baseline in Measure Up 1 and Measure Up 2 were integrated and reported based on observed cases from week 16 (the end of the double-blind period) through week 140 of the blinded extension period; week 16 data for patients randomized to placebo were also reported. Assessments included itch (Worst Pruritus Numerical Rating Scale [WP-NRS]); Eczema Area and Severity Index (EASI); skin pain (AD Symptom Scale [ADerm-SS] Skin Pain); skin symptoms (ADerm-SS 7-item Total Symptom Score [TSS-7]); skin symptom severity (Patient-Oriented Eczema Measure [POEM]); QoL (Dermatology Life Quality Index [DLQI; patients aged ≥ 16 years], and Children's DLQI [CDLQI; patients aged < 16 years]); and sleep, daily activities, and emotional state (AD Impact Scale [ADerm-IS]). Assessed outcomes included achievement of (1) minimal clinically important differences vs baseline (WP-NRS, ADerm-SS Skin Pain, and POEM improvement ≥ 4; ADerm-SS TSS-7 improvement ≥ 28; ADerm-IS Sleep, Daily Activities, and Emotional State improvements ≥ 12, ≥ 14, and ≥ 11, respectively), (2) no/minimal disease burden or impact (WP-NRS 0/1, ≥ 90% improvement from baseline in EASI [EASI 90], DLQI 0/1,and CDLQI 0/1), and (3) simultaneous achievement of EASI 90 and WP-NRS 0/1, an endpoint that aligns with the recently proposed minimal disease activity concept.5 Results Data for 1213 patients (upadacitinib 15 mg, n = 603; upadacitinib 30 mg, n = 610), including 241 adolescents (19.9%) and 972 adults (80.1%), from Measure Up 1 and Measure Up 2 were analyzed. At week 16, over 50% of patients receiving either dose of upadacitinib reported clinically meaningful improvements in PROs; among patients receiving upadacitinib 15 mg and upadacitinib 30 mg, 36.7% and 53.1% achieved WP-NRS 0/1, while 29.0% and 44.1% achieved DLQI 0/1, and 23.5% and 50.0% achieved CDLQI 0/1, respectively. Response rates at week 16 were sustained or improved further through week 140. At week 140, the proportion of patients treated with upadacitinib 15 mg and upadacitinib 30 mg from baseline who achieved clinically meaningful improvements were 64.8% and 70.9% for itch, 74.6% and 81.5% for skin pain, 67.6% and 75.4% for skin symptoms, 89.0% and 94.2% for skin symptom severity, 76.5% and 84.0% for sleep, 79.2% and 84.0% for daily activities, and 78.6% and 82.7% for emotional state, respectively. At week 140, achievement rates with upadacitinib 15 mg and upadacitinib 30 mg were 45.1% and 51.4% for WP-NRS 0/1, 67.3% and 75.6% for EASI 90, 40.5% and 47.1% for simultaneous EASI 90 and WP-NRS 0/1 achievement, 40.2% and 48.5% for DLQI 0/1, and 35.7% and 65.0% for CDLQI 0/1, respectively. Conclusions Patients with moderate-to-severe AD experienced sustained improvements in skin signs/symptoms through 140 weeks while receiving upadacitinib. Rates of long-term PRO improvements were numerically higher with upadacitinib 30 mg compared with upadacitinib 15 mg.

Introduction/Background Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous skin lesions. Some patients with AD continue to experience flares and substantial clinical burden despite the use of systemic therapy. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 versus JAK2, JAK3, and tyrosine kinase 2. Dupilumab is a monoclonal antibody inhibiting interleukin-4 and interleukin-13 signaling. Both upadacitinib and dupilumab are approved in multiple countries for the treatment of moderate-to-severe AD in adolescents and adults. Objectives This monotherapy study assessed the efficacy and safety of upadacitinib, initiated at 15 mg once daily (QD) and dose-escalated to 30 mg QD based on clinical response, compared with dupilumab per its label. Results presented here are based on the Week 16 primary analysis. Methods Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded, head-to-head, multi-center study evaluating upadacitinib vs dupilumab in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use of those therapies was inadvisable. Patients were randomized to upadacitinib 15 mg or dupilumab per its label for 16 weeks of treatment (Period 1), with an extension period to 32 weeks (Period 2) for patients not achieving at least 75% reduction in Eczema Area and Severity Index from baseline (EASI 75) at Week 16. Patients on upadacitinib 15 mg were dose-escalated to 30 mg starting from Week 4 if they had a

Introduction Atopic dermatitis (AD) is a common, chronic inflammatory disease requiring long-term, continuous therapy, yet in real life, patients may need to temporarily interrupt therapy. Objectives To indirectly compare long-term outcomes with lebrikizumab, tralokinumab, and dupilumab, we present an exploratory efficacy index, which accounts for on-drug and off-drug combined outcomes at Week 52. Methods The data set consisted of patients who, after 16 weeks, responded to treatment, defined as achieving either an IGA 0,1 or EASI 75 score, and who were randomized to receive maintenance dosages of lebrikizumab 250 mg Q4W (ADvocate1; ADvocate2), tralokinumab 300 mg Q2W (ECZTRA1; ECZTRA 2), and dupilumab 300 mg QW, Q2W (SOLO-CONTINUE) or were randomized to withdraw these treatments up to Week 52. The efficacy index is based on a weighted combination of response rates at Week 52, using non-responder imputation results, for IGA 0,1 or EASI 75, for patients who were either in the treatment continuation or the withdrawal arm. Here, we report the efficacy index, in which the weight places equal emphasis on continuing or stopping treatment, and we compare the efficacy index of tralokinumab and dupilumab with lebrikizumab. Results The efficacy index (95% CI) for lebrikizumab, tralokinumab, and dupilumab, respectively, was 53% (45%-61%), 45% (37%-53%), and 34% (28%-40%) with IGA 0,1; 63% (55%-71%), 42% (35%-49%), and 51% (45%-57%) with EASI 75. With IGA 0,1, lebrikizumab was statistically different from dupilumab; with EASI 75, lebrikizumab was statistically different from dupilumab and tralokinumab. Conclusions This novel efficacy index, which accounts for the importance of continuing or stopping therapy after Week 16, may be a useful tool to indirectly compare long-term treatment outcomes. Lebrikizumab's higher efficacy index may translate to improved long-term management of AD.

Background Itch is the most burdensome symptom of atopic dermatitis (AD) that severely affects sleep and overall and quality of life.1,2 Rapid control of itch could be instrumental in minimizing disease symptoms and the associated burden for patients.3,4 Nemolizumab, an interleukin-31 (IL-31) alpha antagonist, inhibits the IL-31 pathway of itch and inflammation in AD.5 Objectives To evaluate speed of onset of itch relief and sleep improvements with nemolizumab in moderate-to-severe AD. Methods ARCADIA-1 and ARCADIA-2 were two identical, randomized, double-blinded, placebo-controlled studies. Patients (≥12 years) with moderate-to-severe AD and inadequate response to topical corticosteroids (TCS) were randomized (2:1) to receive nemolizumab 30mg every 4 weeks (60mg baseline loading dose) or matching placebo, both with background TCS of low/medium potency with/without topical calcineurin inhibitors (TCI). Results Significant improvements in itch (least squares [LS] mean±- standard error [SE] change from baseline [CFB] in Peak Pruritus Numeric Rating Scale [PP-NRS]) were noted in nemolizumab-treated vs placebo-treated patients by Day 1 in ARCADIA-1 (-0.9±0.08 vs -0.4±0.10) and ARCADIA-2 (-1.1±0.09 vs -0.4±0.12), reaching -2.4±0.08 vs -1.2±0.11 and -2.3 ±0.09 vs -0.9±0.12 respectively at Day 14 (p<0.001 for all). Significantly greater proportions of nemolizumab-treated vs placebo-treated patients achieved ≥4-point improvement in PP-NRS by Day 2 in ARCADIA-1 (9.4% vs 3.4%, p<0.01) and Day 1 in ARCADIA-2 (8.2% vs 1.9%, p<0.001) and through Day 14 (ARCADIA-1: 22.7% vs 10.6%, p<0.0001; ARCADIA-2: 23.4% vs 6.8%, p<0.0001). Conclusions Treatment with nemolizumab plus TCS/TCI resulted in rapid, statistically and clinically significant improvements in itch in moderate-to-severe AD.

Introduction/Background Biologics and Janus kinase inhibitors (JAKi) are promising treatment options for patients with atopic dermatitis (AD)1; however, no studies, to our knowledge, have evaluated differences in characteristics of patients on these medications in a real-world setting. Objective This study sought to describe the demographics, clinical characteristics, treatment patterns, and disease severity and patient-reported outcome measures of adult patients with AD initiating either a biologic or JAKi in the prospective, non-interventional CorEvitas AD Registry. Methods This cross-sectional study included patients initiating either a biologic (dupilumab or tralokinumab) or JAKi (abrocitinib or upadacitinib) in the CorEvitas AD Registry between 7/21/2020 and 7/31/2023. Patient characteristics were summarized at initiation of therapy using descriptive statistics, overall and by prior experience with biologic/JAKi therapy and systemic therapy (any registry-eligible systemic medication). Additionally, exploratory multivariable modified-Poisson regression was used to identify factors associated with biologic vs. JAKi initiation. Variables were selected by first using bivariate regression, and covariates with p-values ≤0.15 were submitted to a backward selection process. Age, sex, and race were included in the final model for representation purposes. Results The study reported 1,958 initiations, with 1,604 biologic initiations and 354 JAKi initiations. The initiated medication was the first-line systemic among 86.4% of the biologic initiators and 40.7% of the JAKi initiators. Biologic initiators were slightly older than JAKi initiators (mean age 50.7 years, SD 18.5 vs. mean 47.9, SD 17.0 years), with no major differences in sex, race/ethnicity, education, or work status. Differences were seen in history of infections (32.7% in biologic initiators vs. 44.9% in JAKi initiators) and rosacea (12.1% biologics vs. 5.9% JAKi). Furthermore, biologic initiators had greater disease severity than JAKi initiators as measured by body surface area % involvement (mean 26.0, SD 20.2 vs. mean 18.3, SD 19.4), validated Investigator Global Assessment for AD (severe vIGA-AD™, 34.4% vs. 24.6%), Eczema Area and Severity Index (EASI, mean 14.5, SD 12.0 vs. mean 10.7, SD 11.1) and SCoring AD (SCORAD, mean 48.2, SD 19.8 vs. mean 42.2, SD 20.1). Patient-reported outcomes were similar between groups. In adjusted analyses, factors positively associated with JAKi initiation compared to biologics included living in the Midwest US (vs. Northeast US, RR: 1.50, 95% CI: 1.14, 1.97), worst skin pain in 24 hours (RR: 1.05, 95% CI: 1.02, 1.09), and prior use of 1 or 2+ systemic therapies (vs. none, RR: 4.30, 95% CI: 2.29, 8.07 and RR: 5.49, 95% CI: 3.06, 9.84, respectively). Factors positively associated with biologic initiation included having a history of cancer (RR: 0.33, 95% CI: 0.22, 0.49), moderate vIGA-AD™ (vs. clear, RR: 0.74, 95% CI: 0.56, 0.98), hand involvement (RR: 0.73, 95% CI: 0.62, 0.86), and worst itch in 24 hours (RR: 0.97, 95% CI: 0.94, 0.99). Conclusions In this real-world assessment, certain characteristics differed between adult patients with AD initiating either biologics which were most commonly first-line agents or JAKi (more likely used after other systemic agents), although some effect sizes were small and may not be clinically meaningful. Study limitations to consider include that characteristics associated with biologic or JAKi initiation may be influenced by timing of medication approval and availability. These foundational results highlight the importance of individualized patient assessment when deciding among different therapeutic approaches.

Introduction/Background Ritlecitinib, a JAK3/TEC family kinase inhibitor, demonstrated efficacy in a Phase 2b trial of patients with NSV. Objectives To evaluate the efficacy and tolerability of ritlecitinib with or without nbUVB add-on therapy in patients with NSV. Methods In a Phase 2b trial, following a 24-week placebo-controlled dose-ranging period, patients with NSV received ritlecitinib 200 mg for 4 weeks then 50 mg for 20 weeks, with or without nbUVB phototherapy 2x/week. Missing data were handled using observed case (OC) and last observation carried forward (LOCF). Results 43 and 187 patients received ritlecitinib+nbUVB and ritlecitinib-monotherapy, respectively. Nine patients receiving ritlecitinib+nbUVB discontinued due to nbUVB group-specific efficacy criteria requiring >10% improvement in %change from baseline (CFB) in Total-Vitiligo Area Scoring Index (T-VASI) at Week 12. At Week 24, mean (90% CI) %CFB in Facial-VASI (F-VASI) was -69.6 (-79.1, -60.1) vs -55.1 (-59.4, -50.7) (OC; P=0.009) and -57.0 (-65.3, -48.7) vs -51.5 (-55.9, -47.1) (LOCF; P=0.158), for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 60.9% (43.1%, 77.2%) vs 29.2% (22.8%, 35.9%) (OC; P=0.007) and 44.4% (30.2%, 59.1%) vs 27.4% (21.7%, 33.4%) (LOCF; P=0.081) of patients, respectively, achieved ≥75% improvement in F-VASI. Mean (90% CI) %CFB in T-VASI at Week 24 was -46.8 (-54.5, -39.2) vs -24.5 (-28.1, -21.0) (OC; P<0.001) and -29.4 (-36.5, -22.2) vs -21.2 (-25.0, -17.4) (LOCF; P=0.043) for ritlecitinib+nbUVB vs ritlecitinib-monotherapy, respectively. 50.0% (33.3%, 66.7%) vs 15.2% (11.1%, 20.3%) (OC; P<0.001) and 32.6% (22.1%, 44.7%) vs 14.4% (10.6%, 19.0%) (LOCF, P=0.014) of patients, respectively, achieved ≥50% improvement in T-VASI. nbUVB addition to ritlecitinib was well-tolerated with no new safety signals. Conclusions Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well-tolerated. nbUVB may improve ritlecitinib efficacy.