Scholarly Activity

Background: Tapinarof cream 1% once daily (QD) demonstrated significant efficacy in patients down to age 2 years with atopic dermatitis (AD) in the ADORING 1 and 2 phase 3 trials. We report local tolerability outcomes.

Methods: Patients received Tapinarof or vehicle cream QD for 8 weeks. Tolerability was evaluated using patient/parent/caregiver and investigator 5-point Local Tolerability Scales (LTS). Investigators assessed tolerability for sensitive skin areas, including face/neck.

Results: 813 patients were randomized (∼80% pediatric). Mean pretreatment baseline overall LTS scores were similar across groups and trials: 1.0-1.9 (patient-assessed) indicating slight burning/stinging and itching; and 0.3-0.6 (investigator-assessed) indicating no-to-minimal irritation. Tapinarof was well tolerated with improvement from pretreatment baseline and no-to-minimal burning/stinging and itching from first application through Week 8 (patient-reported): mean Week 8 LTS scores were 0.2-0.4 (burning/stinging) and 0.6-0.8 (itching). Investigators reported improvement from pretreatment baseline with no-to-minimal irritation (dryness/erythema/peeling) from first Tapinarof application through Week 8 (mean LTS scores: 0.2 and 0.1 in ADORING 1 and 2, respectively). Across sensitive skin, investigators reported no-to-minimal irritation from first application through Week 8 (mean scores [Tapinarof versus vehicle]: 0-0.3 versus 0-1.0).

Conclusion: Tapinarof was well tolerated locally from first application through Week 8, including on sensitive skin areas. Clinicaltrials.gov numbers NCT05014568, NCT05032859.

BACKGROUND: Ostomates suffer from multiple comorbidities and social stigma, which can be especially debilitating in young patients. TikTok has become a popular platform for this population to establish a community and gain resources. This study aims to characterize intestinal ostomy videos on TikTok.

METHODS: The top 50 videos for search terms "ileostomy," "colostomy," "ostomy," and "stoma" were queried on TikTok. Information was compiled regarding the videos' creators, content type, overall sentiment, and viewer engagement.

RESULTS: A total of 113 videos amongst 38 creators garnered 52,021,700 likes and 370,983 comments. Most videos focused on education (45.5%) and personal stories (22.7%). Creators were predominantly young females (82.0%), with minimal input from healthcare professionals (3% of videos). Sixty-nine (61%) of videos had responses with further questions.

CONCLUSIONS: Our study reveals a gap between interest and availability of professional educational material regarding intestinal ostomies. Addressing this deficiency may improve patient acceptance, bystander understanding, and its negative stigma.

Adenoid cystic carcinoma (ACC) is a rare cancer that most commonly occurs in the salivary glands, making up approximately 2-4% of all head and neck malignancies. Treatment for ACC varies, with combinations of surgical excision, adjuvant radiotherapy, and chemotherapy reported in the literature. In this study, we aim to assess ACC recurrence rates with Mohs Micrographic Surgery (MMS) treatment compared to traditional wide local excision (WLE). In June of 2024, a comprehensive review of the literature was performed using the following keywords: "Adenoid Cystic Carcinoma" and/or "Mohs Micrographic Surgery" and/or "MMS" and/or "excision." Between the two databases, 25 articles were identified which included a total of 30 patients. Among all the articles, 30 procedures were documented - 8 MMS and 22 WLE. Patients with ACC treated with WLE had a higher rate of recurrence (40.9%) compared to those treated with MMS (12.5%). Limitations include a small number of tumors treated and reporting bias. MMS for the treatment of ACC demonstrated a decreased recurrence rate compared to WLE. Further studies with larger sample sizes are needed to confirm the benefit of MMS over WLE.

Itch is a prominent symptom in many cutaneous disorders, including atopic dermatitis (AD), prurigo nodularis, and psoriasis. Itch is also a common but overlooked concern in patients with hidradenitis suppurativa (HS). Currently, the mechanisms underlying itch in HS remain unclear. To gain a better understanding, we reviewed the literature on pruritus in HS and other itch-predominant disorders, AD, and psoriasis. In HS, psoriasis, and AD, we found that itch often co-localized with pain and occurred more frequently at night. Furthermore, itch was found to negatively affect sleep and increase the risk for comorbid psychiatric disorders in HS, psoriasis, and AD. However, HS-, psoriasis-, and AD-related itch differ in temporality. Itch in AD is often described as chronic, while itch in HS and psoriasis is often described as episodic. HS-associated itch is likely multifactorial, and several mechanisms have been proposed including peripheral sensitization, central sensitization, and neuroinflammation. Prior studies in HS highlight enhanced IgE production and a dense infiltration of mast cells, along with a variety of cytokines and chemokines. Furthermore, alterations in the skin microbiome may contribute to itch in HS. To date, few therapies have been studied to treat itch in HS. Given the efficacy of several biologics and small molecules in treating itch in AD and psoriasis, similar agents may be explored in future HS studies. Alternative therapies to target neurological and psychiatric contributions to itch may include anticonvulsants, cannabinoids, and nonpharmacological treatments. In conclusion, pathomechanisms of itch in HS remain to be fully elucidated. However, we can draw on lessons from other pruritic disorders to begin addressing the symptom of it and identify important questions for future study.

Few studies discuss the co-management of vitiligo and acquired hyperpigmentation disorders (AHD) such as melasma, erythema dyschromicum perstans, post-inflammatory hyperpigmentation, drug-induced hyperpigmentation, and lichen planus pigmentosus. This review discusses clinical studies examining co-management strategies and identifies current practice gaps. Dermatology Life Quality Index scores are higher in individuals with vitiligo or melasma. It is plausible that populations experiencing both conditions may exhibit worsened psychological outcomes because of stigmas and perceived social beauty standards. Standard treatments for vitiligo aim to increase pigmentation, while AHD treatments target decreasing pigmentation, causing potential worsening of contrast between multiple skin tones for patients experiencing both disorders. Tretinoin may prevent narrowband ultraviolet B (NBUVB)-induced hyperpigmentation in patients with vitiligo without altering treatment response and is also beneficial for managing AHD. In addition, the use of oral tranexamic acid to treat melasma does not diminish the response to NBUVB phototherapy. Platelet-rich plasma (PRP) injections and oral Polypodium leucotomos extract may also be beneficial for comanaging vitiligo and AHD. However, practice guidelines are needed to optimize care for this patient population.

BACKGROUND: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis.

OBJECTIVE: To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa.

METHODS: We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls. We profiled circulating inflammatory proteins using Olink High-throughput proteomics and determined genetic ancestry from whole-genome sequencing data.

RESULTS: Using linear regression, we identified novel proteins associated with HS after adjusting for age, sex, and ethnicity. Our analysis also revealed differences in the inflammatory proteome linked to disease severity. Specifically, we found that plasma IL6 levels can distinguish between different Hurley stages, indicating that IL6 may serve as a marker of disease severity. Additionally, we observed variations in inflammatory protein levels based on genetic ancestry: patients with predominantly African ancestry exhibited higher levels of inflammatory proteins associated with neutrophilic inflammation, while those with predominantly European ancestry showed increased levels of Th1-related inflammatory proteins.

LIMITATIONS: Single-center study. Limited sample size. Unable to account for treatment status or comorbidities that may influence the level of inflammatory cytokines.

CONCLUSION: Genetic ancestry and disease severity influence the plasma inflammatory profile in patients with HS.

BACKGROUND: Ruxolitinib cream has demonstrated anti-inflammatory and antipruritic activity and was well tolerated in a phase 3 study in patients aged 2-11 years with mild to moderate atopic dermatitis (AD).

OBJECTIVE: This study examined the safety, tolerability, pharmacokinetics, efficacy, and quality of life (QoL) with ruxolitinib cream under maximum-use conditions and with longer-term use.

METHODS: Eligible patients were aged 2-11 years with moderate to severe AD [Investigator's Global Assessment (IGA) score 3-4], and ≥ 35% affected body surface area (BSA). Patients applied 1.5% ruxolitinib cream twice daily to all baseline-identified lesions during the 4-week maximum-use period, then to active lesions only up to week 52 (patients with ≤ 20% affected BSA from week 8). Safety was assessed by frequency and severity of adverse events. Pharmacokinetic parameters were assessed as secondary endpoints, and efficacy and QoL were exploratory endpoints.

RESULTS: Overall, 29 patients (median age 5 years) were enrolled. Treatment-emergent adverse events were reported in 9/29 patients (31.0%); there were no adverse events of special interest (i.e., no serious infections, malignancies, major adverse cardiovascular events, or thromboses) during the study period. Mean steady-state plasma concentration during the maximum-use period was below the known half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in adults. Reductions in affected BSA and IGA observed at week 4 were sustained with as-needed use through 52 weeks. Improvements in patient-reported outcomes and QoL measures were consistent with efficacy results.

CONCLUSION: These results support the safety of ruxolitinib cream in children (2-11 years) with AD, including those with extensive disease, and are consistent with previous efficacy findings.

GOV IDENTIFIER: NCT05034822, first registered 30 August 2021.

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.