bluuebunny/crossref_metadata_2025_split huggingface dataset:
P64 Efficacy of baricitinib in patients with different degrees of severe alopecia areata: 52-week results from BRAVE-AA1 and BRAVE-AA2
Authors: Farrant Paul , Egeberg Alexander , Ito Taisuke , Gittens Beatrice , Chiasserini Chiara , Yu Guanglei , Durand Frederick , Huang Yu-Huei 
Published: June 2023

Abstract
Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, demonstrated efficacy in adults with severe alopecia areata (AA) over 36 weeks in two phase III, randomized, double-blind, placebo-controlled trials, BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259). Using integrated data from the long-term extension periods of both trials, we report treatment response to baricitinib by the AA severity subgroup based on the Severity of Alopecia Tool (SALT) score over 52 weeks. Patients randomized to baricitinib at baseline (n = 855) retained their treatment allocation (2 mg/4 mg) through to week 52 in both trials and were included in week 52 analyses; placebo nonresponders were rescued at week 36. Severity of AA at baseline was defined as severe (SALT score 50–94) or very severe (SALT score 95–100). Key inclusion criteria were SALT score ≥ 50, current AA episode lasting &gt; 6 months to &lt; 8 years without spontaneous improvement within 6 months prior to screening, and no previous inadequate response to oral JAK inhibitors. Efficacy endpoints included the proportion of patients achieving a SALT score ≤ 20 and the proportion of patients achieving Clinician-Reported Outcome (ClinRO) Measure for Eyebrow/Eyelash Hair Loss™ 0,1 (no, minimal gaps) with ≥ 2-point improvement from baseline among patients with baseline scores 2,3 (significant gaps, no notable eyebrows/eyelashes). Analyses were presented descriptively for each subgroup up to week 52. Nonresponder imputation was used for missing data. Data collected after permanent study drug discontinuation or at remote visits due to the COVID-19 pandemic were excluded. In total, 1200 patients were enrolled (BRAVE-AA1, n = 654; BRAVE-AA2, n = 546). At baseline, the overall mean (SD) age was 37.5 (12.9) years; 60.7% were female and 46.8% and 53.2% of patients had severe and very severe AA, respectively. At week 52, a SALT score ≤ 20 was achieved by 36.1% and 51.2% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with severe AA and 12.4% and 27.7% of patients on baricitinib 2 mg and baricitinib 4 mg, respectively, with very severe AA. Eyebrow/Eyelash Hair Loss™ scores 0,1 with ≥ 2-point improvement from baseline at week 52 were achieved by 19.4% and 26.0% (baricitinib 2 mg) and 37.5% and 38.5% (baricitinib 4 mg) of patients with severe AA and 24.3% and 25.3% (baricitinib 2 mg) and 47.6% and 48.1% (baricitinib 4 mg) of patients with very severe AA. Following 52 weeks of treatment with both baricitinib doses, clinical responses of SALT score ≤ 20 were observed both in patients with severe and very severe AA. Proportions of patients achieving full coverage or minimal gaps in eyebrows and eyelashes were similar at week 52, regardless of scalp hair-loss severity.
Funding sources: Eli Lilly and Company.
P65 Vitamin D deficiency is associated with atopic dermatitis severity in a Bangladeshi population living in the UK
Authors: McCarthy Rebecca L , Thomas Bjorn R , Tawfik Soha S , Atkar Ravinder , McDonald Bryan , Dhoat Sasha , Hughes Aaron , O’Toole Edel 
Published: June 2023

Abstract
Atopic eczema is a common chronic inflammatory skin condition with considerable heterogeneity. South Asian people living in the UK frequently have low vitamin D levels, and those with atopic disease can present with severe eczema. The association between vitamin D insufficiency and eczema severity and the role of vitamin D supplementation in atopic eczema is inconsistent, and it is under-researched in people with Asian ancestry living in low-ultraviolet (UV) areas. This cross-sectional study investigates the association between serum 25-hydroxy vitamin D3 [25(OH)D3] and eczema severity in a cohort of South Asian children and young adults living in the UK. Eligible participants were Bangladeshi children and young adults aged 0–30 years with eczema, participating in the THEA study. Data for the study were collected via parent/patient self-reporting, clinical history and examination and hospital databases. Levels of 25(OH)D3 were documented retrospectively, if available, from hospital databases. Eczema severity was classified by an Eczema Area and Severity Index (EASI) score less than or greater than 10. Multivariate logistic regression was used to adjust for confounding factors. In total, 682 patients were recruited between May 2018 and December 2021. The EASI score was available for 681 participants [mean (SD) 7.9 (9.1)] and 25(OH)D3 results were available for 49.7% (n = 339). Eighty-four per cent were deficient (&lt; 25 nmol L−1) or insufficient (&lt; 50 nmol L−1) in 25(OH)D3. Vitamin D3 levels were inversely correlated with the EASI score (Spearman’s rank R2 = –0.22; P &lt; 0.001). After adjustment, there was a significant association between eczema severity (EASI &gt; 10) and lowest 25(OH)D3 [odds ratio (OR) 0.973, 95% confidence interval (CI) 0.956–0.988; P &lt; 0.001], working class (OR 0.542, 95% CI 0.295–0.991; P = 0.047), previous immunosuppression/biologic therapy (OR 2.432, 95% CI 1.189–5.077; P = 0.016), mild-to-moderate potency topical steroid use on the face and neck (OR 3.566, 95% CI 1.730–7.696; P &lt; 0.001) and topical calcineurin inhibitor use on the face and neck (OR 3.421, 95% CI 1.140–10.288; P = 0.027). These findings demonstrate an inverse correlation between 25(OH)D3 level and eczema severity in a cohort of exclusively South Asian children and young adults living in a low-UV region. Vitamin D plays a role in the modulation of proteins required for skin barrier function and regulation of the innate immune system, suggesting that vitamin D deficiency in this population may contribute to inflammation in the skin. Further research on the role of vitamin D supplementation in atopic eczema, particularly in people with skin of colour, is required.
P68 Liver fibrosis is independent of methotrexate use in patients with moderate-to-severe psoriasis
Authors: Babakinejad Parastoo , Lapsley Rebecca , Foster Lara , McPherson Stuart , Pearce Mark , Reynolds Nick , Slack Emma , Weatherhead Sophie , Hampton Philip 
Published: June 2023

Abstract
Methotrexate has been implicated for liver disease in patients with psoriasis for many years. Liver fibrosis (LF) has various established risk factors, but data on the impact of methotrexate on LF in patients with psoriasis are lacking. This cross-sectional cohort study aimed to determine the prevalence of LF using noninvasive LF markers in patients with psoriasis, and to evaluate the relationship between LF and the cumulative dose of methotrexate and other liver disease risk factors. Adults with moderate-to-severe chronic plaque psoriasis diagnosed by a dermatologist, who were selected for a LF assessment, were recruited from dermatology clinics in a tertiary centre between June 2020 and March 2021. Data were recorded as part of standard clinical care and at the time of recruitment. Patients underwent transient elastography to evaluate LF. Three values for liver stiffness measurement (LSM) were used, indicating ≥ mild LF (≥ 7 kPa), ≥ moderate LF (≥ 7.9 kPa) and ≥ advanced LF (≥ 9.5 kPa). Both continuous and categorical LSM values were used for evaluation. A total of 225 patients were included [median age 48, interquartile range (IQR) 37–57, 51% female]. Fifty-six per cent had a body mass index (BMI) ≥ 30 kg m−2, and the median alcohol use disorders identification test (AUDIT) score was 4 (IQR 1–7, 23% score ≥ 8). Ninety-one per cent had received methotrexate for a median duration of 36 months (IQR 14–78). Prevalence rates of LF were 31%, 21% and 13% using LSM ≥ 7 kPa, ≥ 7.9 kPa and ≥ 9.5 kPa, respectively. There was no association between methotrexate and continuous LSM values [unadjusted coefficient 0.16, 95% confidence interval (CI) 0.49–0.82; P = 0.63] or using the categorical LSM cutoff values: 7 kPa (unadjusted coefficient 1.06, 95% CI 0.98–1.15; P = 0.19), 7.9 kPa (unadjusted coefficient 1.03, 95% CI 0.94–1.12; P = 0.58) and 9.5 kPa (unadjusted coefficient 1.01, 95% CI 0.91–1.12; P = 0.84). Similarly, no significant relationship was found when adjusting for other risk factors for LF. The following risk factors were associated with higher LSM values: BMI (P &lt; 0.001), waist circumference (P &lt; 0.001), metabolic syndrome (P &lt; 0.001), AUDIT score (P = 0.020) and Fib-4 score (P = 0.03). This study confirms a high prevalence of significant LF in patients with moderate-to-severe psoriasis. More importantly, it shows that cumulative methotrexate was not associated with LF, and other risk factors including BMI, waist circumference, metabolic syndrome, alcohol intake and Fib-4 score are important predictors for LF. The findings suggest that these risk factors should be assessed in this group of patients to identify patients requiring regular liver health monitoring. Further research is needed to determine whether methotrexate contributes to the progression of LF in the context of pre-existing LF.
P70 A randomized open-label study to compare two different dosage regimens of oral tranexamic acid in treatment of moderate-to-severe facial melasma
Authors: Keshavamurthy Vinay , Bhattacharjee Rajsmita , Hanumanthu Vinod , Thakur Vishal , Bishnoi Anuradha , Parsad Davinder , Kumaran Muthu Sendhil 
Published: June 2023

Abstract
Oral tranexamic acid (TXA) demonstrates promising results in melasma treatment; however, TXA dosing in melasma management has been a cause for persistent speculation. There is still no consensus to guide dosing, duration of TXA therapy and need for maintenance treatment. Our aim was to evaluate and compare the efficacy of two different TXA dosing regimens, 250 mg twice daily vs. 500 mg twice daily in patients with melasma using the modified Melasma Area and Severity Index (mMASI) score. This was a randomized open-label study involving 50 patients aged &gt; 18 years with moderate-to-severe melasma. Patients were randomized into group A (oral TXA 250 mg twice daily) and group B (oral TXA 500 mg twice daily) for 12 weeks and later followed-up monthly to 24 weeks. The primary outcome measure was the proportion of patients achieving a 75% reduction in mMASI (mMASI-75) at 12 weeks from baseline, and a reduction in mMASI and Melasma Quality of Life (MelasQOL) score at 12 and 24 weeks. The proportion of patients achieving mMASI-75 at 12 weeks was 20% in group A and 25% in B (P = 0.71). Both groups showed a statistically significant reduction in mean (SD) mMASI [4.8 (2.2) in group A and 6.8 (3.4) in group B; P = 0.02] at 12 weeks. mMASI remained stable after 12 weeks and was 4.9 (2.43) and 4.92 (2.85) in groups A and B, respectively, at 24 weeks (P = 0.97). The mean (SD) percentage reduction rates in MelasQOL in groups A and B were 41.8 (15.3) and 29.5 (21.5), respectively (P = 0.03). No adverse effects were observed in either group. Both dosing regimens showed comparative efficacy in terms of mMASI reduction at 12 weeks. The improvements achieved were well maintained even after 12 weeks of discontinuing treatment. Hence, lower doses of TXA (i.e. 250 mg twice daily) are equally as effective and safe as higher doses (i.e. 500 mg twice daily). With regard to maintenance dosing, few patients relapsed; hence, not all patients will require tapering or dosing maintenance.
P73 Laboratory safety from a 16-week phase III study of dupilumab in patients aged 6 months–5 years with moderate-to-severe atopic dermatitis
Authors: Paller Amy S , Cork Michael J , Wollenberg Andreas , Siegfried Elaine C , Gonzalez Mercedes E , Lockshin Benjamin , Khokhar Faisal A , Chen Zhen , Gonzalez Tayler , Simcox Elizabeth , Prescilla Randy 
Published: June 2023

Abstract
Previous studies of dupilumab treatment in adults, adolescents and children aged 6–11 years with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful changes in laboratory parameters. Here, we evaluate laboratory safety data for dupilumab-treated children aged 6 months–5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL (NCT03346434 part B), a placebo-controlled phase III trial, 162 children aged 6 months–5 years with moderate-to-severe AD were randomized to receive dupilumab 200 mg or 300 mg every 4 weeks (n = 83) based on baseline weight (200 mg: ≥ 5 to &lt; 15 kg; 300 mg: ≥ 15 to &lt; 30 kg), or placebo (n = 79) for 16 weeks. Low-potency topical corticosteroids were initiated from day −14. At baseline, mean (SD) haematology parameters were similar in both treatment groups: eosinophils [dupilumab: 1.1 × 109 cells L−1 (0.7); placebo: 1.1 × 109 cells L−1 (0.7)], platelets [dupilumab: 397.7 × 109 cells L−1 (103.2), placebo: 385.6 × 109 cells L−1 (112.9)] and neutrophils [dupilumab: 3.54 × 109 cells L−1 (1.56); placebo: 3.85 × 109 cells L−1 (1.73)]. Mean (SD) counts of neutrophils [dupilumab: 3.18 × 109 cells L−1 (1.94); placebo: 3.79 × 109 cells L−1 (1.91)] remained within the normal reference interval (RI) at week 16. Mean (SD) change in platelet count at week 16 was −16.3 × 109 cells L−1 (78.5) in the dupilumab group and 17.4 × 109 cells L−1 (106.6) in the placebo group. In the dupilumab group, the mean (SD) change in eosinophil count increased at week 4 [0.48 × 109 cells L−1 (1.8)] and trended downward by week 16 [0.31 × 109 cells L−1 (1.4)], while minimal changes were noted in the placebo group at week 4 [0.1 × 109 cells L−1 (0.7)] and week 16 [−0.2 × 109 cells L−1 (0.7)]. The mean (SD) values for creatine kinase [dupilumab: 144.2 U L−1 (84.8); placebo: 130.7 U L−1 (46.39)], alkaline phosphatase [dupilumab: 273.4 U L−1 (80.01); placebo: 233.2 U L−1 (65.98)] and lactate dehydrogenase [dupilumab: 283.8 U L−1 (44.74); placebo: 317.4 U L−1 (67.58)] at week 16 remained within the normal RI in all treatment groups. Two patients treated with dupilumab reported cases of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of study treatment. No clinically meaningful changes in haematology or chemistry laboratory safety parameters in children aged 6 months–5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this population.
Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
P78 Amyopathic dermatomyositis: a retrospective review of 21 cases
Authors: Sambi Pavan , Khan Wajeeha , Laws Phil 
Published: June 2023

Abstract
Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, which can be associated with malignancy and lung disease. We report a retrospective review of 21 cases of ADM presenting to a tertiary clinic. We discuss the clinical presentations, investigation, and cancer and lung associations. Patients were included if they met the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for ADM. We identified 21 patients with ADM (16 women and five men). Mean age at diagnosis was 61 years (range 35–81). Clinical features were as follows: Gottron papules (n = 15; 71%), nailfold involvement (n = 16; 76%), heliotrope rash (n = 12; 57%), shawl sign (n = 11; 52%), Raynaud phenomenon (n = 9; 43%), scalp disease (n = 6; 29%) and calcinosis (n = 3; 14%). Antinuclear antibody (ANA) was positive in 76% of patients (n = 16) and 41% (n = 9) had myositis-specific antibodies. Four patients had a prediagnosed malignancy. One patient had prostate cancer detected on malignancy screen. One nerve sheath tumour was diagnosed within 1 year of ADM diagnosis and one cholangiocarcinoma within 3 years. Three patients were found to have mild lung fibrosis, but none was found to have severe interstitial lung disease. Patients were treated with corticosteroids (n = 16), hydroxychloroquine (n = 11), metho­trexate (n = 10), mycophenolate (n = 6), cyclophosphamide (n = 3), rituximab (n = 3), intravenous immunoglobulin (n = 3), mepacrine (n = 2), azathioprine (n = 1), ciclosporin (n = 1) and thalidomide (n = 1). In conclusion, in our study, a female preponderance and cutaneous findings involving extremities were seen in the majority of patients (95%), in keeping with other published data (el-Azhary RA, Pakzad SY. Amyopathic dermatomyositis: retrospective review of 37 cases. J Am Acad Dermatol 2002; 46:560–5). Our study further highlights the heterogeneity of cutaneous clinical presentation of ADM, which is broadly consistent with other reported cohorts [el-Azhary and Pakzad; Tang K, Zhang H, Jin H. Clinical characteristics and management of patients with clinical amyopathic dermatomyositis: a retrospective study of 64 patients at a tertiary dermatology department. Front Med (Lausanne) 2021; 8:783416]. We report high levels of hand and nail involvement, emphasizing the need for formal assessment of hands, including dermoscopy of nails. ANA was positive in 76% of patients; other reported data suggest that it is positive in 31.6–71% (el-Azhary and Pakzad; Tang et al.). Although previous studies have found myositis-specific antibodies in 87.5% (Tang et al.), only 42% in our cohort had positive antibodies; therefore, a high index of suspicion is required to detect cases and appropriately screen for associated morbidity (lung disease and malignancy). In addition, a third of patients had associated malignancy prediagnosed or within 3 years of diagnosis, highlighting the importance of baseline screening and ongoing follow-up.
P84 Efficacy and safety of lebrikizumab at 16 weeks: pooled analyses from ADvocate1 and ADvocate2 phase III trials in patients with moderate-to-severe atopic dermatitis
Authors: Warren Richard B , Silverberg Jonathan I , Guttman-Yassky Emma , Thaçi Diamant , Irvine Alan , Gold Linda Stein , Blauvelt Andrew , Simpson Eric L , Chu Chia-Yu , Liu Zhuqing T , Lima Renata Gontijo , Pillai Sreekumar , Gil Esther Garcia , Seneschal Julien 
Published: June 2023

Abstract
Lebrikizumab (LEB) is a high-affinity monoclonal antibody targeting interleukin (IL)-13, preventing IL-13 signalling via the IL-4Rα/IL-13Rα1 receptor complex. Here, we report 16-week efficacy and safety outcomes of LEB monotherapy in patients with moderate-to-severe atopic dermatitis from two 52-week, randomized, double-blinded, placebo-controlled phase III trials, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Eligible adults and adolescents (aged 12–17 years, weighing ≥ 40 kg) from ADvocate1 and ADvocate2 were randomized (2 : 1) to subcutaneous LEB 250 mg (500 mg loading dose at baseline and week 2) or placebo every 2 weeks (Q2W). Efficacy analyses included proportions of patients achieving Investigator’s Global Assessment (IGA) 0/1 and Eczema Area and Severity Index (EASI)-75 (coprimary endpoints), EASI-90, and pruritus numeric rating scale (NRS) ≥ 4-point improvement from baseline to week 16. This was a pooled analysis of ADvocate1 and ADvocate2, where IGA 0/1 and EASI-75 and EASI-90 were analysed in 564 and 287 patients (LEB 250 mg and placebo), respectively, and pruritus NRS in 516 and 264 patients, respectively. Cochran–Mantel–Haenszel with Markov chain Monte Carlo multiple imputation was performed. Patients treated with LEB 250 mg and placebo for 16 weeks achieved, respectively, IGA 0/1 response rates of 38.1% (n = 215) and 11.7% (n = 34; P &lt; 0.001); EASI-75 responses of 55.4% (n = 313) and 17.2% (n = 49; P &lt; 0.001); EASI-90 responses of 34.5% (n = 195) and 9.2% (n = 26) (P &lt; 0.001); and pruritus NRS ≥ 4-point improvement responses of 42.9% (n = 221) and 12.2% (n = 32; P &lt; 0.001). The percentage of patients reporting one or more treatment emergent adverse event(s) was lower in the LEB group (49.6%) than in the placebo group (59.0%; P = 0.009). These data suggest that LEB 250 mg Q2W for 16 weeks is an efficacious and safe treatment option for adult and adolescent patients with moderate-to-severe atopic dermatitis.
Funding sourcesThis study was funded by Dermira, a wholly owned subsidiary of Eli Lilly and Company. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including atopic dermatitis, in Europe. Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of world outside Europe.
P93 Dupilumab treatment in children with moderate-to-severe atopic dermatitis increases levels of bone mineralization biomarkers
Authors: Irvine Alan D , Paller Amy S , Horowitz Julie E , Farrell Annamaria , Hatsell Sarah , Ehmann Peter , McDonald Robert , Marco Ainara Rodriguez , Tian Tingting , Cyr Sonya L 
Published: June 2023

Abstract
Children with atopic dermatitis (AD) are at risk for lower bone mineral density (BMD) and lower alkaline phosphatase (ALP) levels than healthy children. Low BMD and ALP in children could contribute to a higher lifetime prevalence of fractures, osteopenia and osteoporosis. Dupilumab is a fully humanized monoclonal anti-interleukin (IL)-4R antibody approved for the treatment of AD in children. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone mineralization in children aged 6–12 years with moderate-to-severe AD vs. reference intervals (RIs). Analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS, a phase III placebo-controlled trial of 16 weeks (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454), an open-label extension trial in which eligible patients received dupilumab until week 52. Biomarkers, including bone ALP (BALP), procollagen type 1 N-terminal propeptide (P1NP), C-terminal crosslinking telopeptide of β-1 collagen (β-CTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1), were analysed at baseline, 8, 12 and 16 weeks; only BALP was measured at 52 weeks. Both dupilumab dosing regimens led to significant increases in geometric mean (SE) levels of BALP at 8, 12 and 16 weeks compared with placebo. For the 100/200-mg Q2W group, at week 8 the BALP level was 72.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P &lt; 0.0001), at week 12 it was 74.7 (1.03) μg L−1 vs. 64.3 (1.05) μg L−1 (P &lt; 0.001) and at week 16 it was 78.0 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P &lt; 0.001). For the 300-mg Q4W group, at week 8 the BALP level was 76.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P &lt; 0.001), at week 12 it was 73.3 (1.04) μg L−1 vs. 64.3 (1.05) μg L−1 (P = 0.002) and at week 16 it was 77.3 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P &lt; 0.001). At 52 weeks, BALP levels were statistically significantly increased compared with baseline [placebo vs. placebo transitioned to dupilumab: 64.2 (1.04) μg L−1 vs. 82.9 (1.04) μg L−1 (P &lt; 0.001); 100/200 mg Q2W: 62.0 (1.05) μg L−1 vs. 83.8 (1.03) μg L−1 (P &lt; 0.001); 300 mg Q4W: 64.1 (1.04) μg L−1 vs. 78.7 (1.04) μg L−1 (P &lt; 0.001)] and also increased within RIs. From baseline to week 16, OC, P1NP and β-CTX levels improved from below to within the RIs, and levels of IGF-1 increased from the lower limit of the RI. However, data points were limited due to insufficient sera volumes, preventing statistical analyses for these biomarkers. The overall results suggest an increase in bone mineralization biomarkers in paediatric patients with moderate-to-severe AD following dupilumab treatment.
Funding sources:research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.