tbuckley/cabot-search huggingface dataset:
P74 Guselkumab clinical super-response is associated with faster normalization of blood and skin pathology: data from the Phase 3b GUIDE trial
Journal: British Journal of Dermatology (2024)

Abstract The ongoing GUIDE trial (NCT03818035) examines the clinical and immunological impact of an extended dosing interval of guselkumab [an interleukin (IL)-23p19 subunit inhibitor] in patients with moderate-to-severe plaque-type psoriasis. A mechanistic substudy was conducted to explore the molecular differences in the skin and blood of ‘super-responder’ (SRe) and non-SRe patients. SRes were defined as patients achieving a psoriasis area and severity index (PASI) = 0 at both Week [W]20 and W28 following guselkumab treatment. RNA-sequencing was performed on non-lesional (at W0) and lesional skin samples (at W0, W4, W28, and W68) along with serum analyses of matching timepoints. Published gene sets related to psoriasis skin and cytokine-stimulated keratinocytes were used for gene set variation analysis. At W0, ∼1100 protein-coding transcripts were upregulated in lesional vs. non-lesional skin, and ∼3000 protein-coding transcripts were downregulated in lesional vs. non-lesional skin. Following treatment with guselkumab, robust pharmacodynamic changes were observed for immune- and psoriasis inflammation-related gene signatures. Faster changes were observed in SRes vs. non-SRes. Signatures related to psoriasis skin inflammation, IL-17-stimulated keratinocyte response, T-helper (Th)17 cells, and many keratinocyte subtypes (differentiated, proliferating and inflamed keratinocytes) were more significantly reduced in SRes vs. non-SRes as early as W4. By W28, all signatures that were upregulated at baseline in lesional vs. non-lesional skin were normalized in SRes, including molecular scar skin and Th17 pathway signatures. In contrast, among non-SRes, molecular scar and immune-cell-regulated signatures (including macrophage, Th22, mucosal-associated invariant T cells, and CD4+ T cells) were &amp;lt;75% normalized at W28. In both SRes and non-SRes, signatures initially downregulated in lesional vs. non-lesional skin at W0, including those for adipocytes, smooth muscles, meta-analysis-derived psoriasis downregulated genes, and IL-17-stimulated KC downregulated genes, represent the few signatures that did not return to non-lesional skin levels after 68 weeks of guselkumab treatment. Consistent with the effect of guselkumab on inflammatory processes in the skin as observed via RNA sequencing, guselkumab treatment decreased the serum levels of several inflammatory mediators as early as W4. The levels of IL-17A, IL-17F and IL-22 were comparable in SRes and non-SRes, while the reduction in beta defensin-2 level was more pronounced in SRes at W4 and W28. These reductions were maintained to W68. In summary, molecular analyses of SRes and non-SRes in the GUIDE clinical trial show kinetic and quantitative differences in the response to guselkumab treatment.
FC26 The MEditerranean Diet and Time-Restricted Eating Dietary Interventions for Psoriasis (METRED-P) study: an interim analysis of the first UK-based diet intervention trial
Journal: British Journal of Dermatology (2024)

Abstract There is no dietary guidance for people living with psoriasis in the UK, and evidence from randomized controlled trials (RCTs) is lacking. To address the knowledge gap on the efficacy of anti-inflammatory interventions such as the Mediterranean diet (MD) and Time-Restricted Eating (TRE), the MEditerranean Diet and Time-Restricted Eating Dietary interventions for Psoriasis (METRED-P) study aimed to examine the feasibility and collect pilot data subject to an MD, MD with TRE, or a TRE diet on psoriasis severity, life quality, and body composition. The METRED-P study (NCT05820698) was a single-centre parallel-arm feasibility pilot trial recruiting participants between June 2023 and July 2024. Inclusion criteria consisted of a psoriasis area and severity index (PASI) &amp;gt;5, body mass index (BMI) of 20–40 kg/m2, no systemic treatments (or on stable systemic treatments &amp;gt;6 months), and no underlying conditions. Participants were randomized by variance minimization to a TRE diet (10-h eating with 14-h fasting), an MD (rich in fruits, vegetables, whole-grains, fish, olive oil, and nuts) or an MD with TRE, and attended clinic visits at baseline and 12 weeks for repeat measures. Psoriasis severity was assessed with the PASI, life quality with the Dermatology Life Quality Index (DLQI), and body composition with the Tanita® scale. Twenty-four participants (60% female and 40% male) enrolled in the METRED-P study, and 10 participants completed the study to date. Participants reported a mean (SD) age of 44 (10) years, BMI of 28 (6) kg/m2, and baseline PASI of 10 (4). One-way analysis of variance showed statistically significant mean changes in total body fat % and in DLQI scores (P &amp;lt; 0.05). Post hoc analyses showed TRE improved DLQI scores compared with the MD, −11 (4) points, P &amp;lt; 0.05. TRE resulted in the greatest mean reductions in PASI −5 (4), compared with the MD −2 (3) and MD with TRE −1 (3), but statistical significance was not reached in this interim analysis. This is the first study clinically testing the MD and TRE in people with psoriasis. Whilst the METRED-P study is anticipated to end in October 2024, interim analyses illustrate favourable effects of TRE on life quality; an often-overlooked patient outcome. Given the ease and low cost of administration, TRE could be a consideration for people living with psoriasis. These pilot data will enable sample size calculations for fully powered RCTs to confirm these preliminary findings.
FC25 Interdisciplinary clinical boards on chronic inflammatory diseases: beneficial effects on psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Many chronic inflammatory diseases may involve various organs of the human body and need interdisciplinary care for the benefit of affected patients. Therefore, interdisciplinary clinical boards on chronic inflammatory diseases (ICB) are increasingly established, yet their prerequisites with regard to the composition of participants, diseases to be covered, frequency of meetings and administration as well as documentation still need to be clarified. In 2016 an ICB was inaugurated at the University Hospital of Erlangen as part of Deutsches Zentrum Immuntherapie (DZI). During once-weekly meetings with compulsory and minimal participation of a dermatologist, rheumatologist and gastroenterologist between 5 and 15 patients are discussed and diagnostic as well as therapeutic issues decided. The meeting parameters between 2020 and 2024 have been analysed to evaluate the quality and outcome of ICB activities. Within this interval, 1067 consultations took place covering 804 patients, 13% below the age of 18 years. The main topics were induction of systemic treatment in 15% of cases and change of therapy in 34%. Diagnostic issues were raised in 10% of cases. Twenty-four percentage of requests were dermatologic, 11% gastroenterologic and 8% rheumatologic. Psoriasis accounted for 22% of cases, psoriasis arthritis 2%, and inflammatory bowel disease 9%. Sixty-two percentage of ICB-recommendations were followed, and 24% were not followed. Recommendations by ICB resulted in a clinical improvement of disease in 38% of cases, and diagnostic procedures were followed in 27% of cases. This study documents a positive structural and process quality, whereas the quality of results with regard to the improvement of disease activity still needs to be ameliorated.
FC20 Automating psoriasis area and severity index assessment from real-world images using Vision Transformers
Journal: British Journal of Dermatology (2024)

Abstract The psoriasis area and severity index (PASI) is the gold standard for assessing psoriasis severity but is time-consuming, subjective, poorly reproducible, and requires face-to-face interaction between clinician and patient. Automating PASI assessments using deep learning-based image analysis may provide a more objective, efficient measure of disease severity in trial and real-world settings. Most studies have used Convolutional Neural Networks.1 However, Vision Transformers (ViTs) are sophisticated deep learning models that have shown unprecedented capabilities in image analysis, including classifying skin lesions from dermoscopic images and 3D image (computed tomography/magnetic resonance imaging scan) analysis. We sought to develop and evaluate a ViT model for automated PASI using images. Following consent, adults with chronic plaque psoriasis were recruited via a UK national specialized psoriasis service (04/2021–05/2024). Professional studio photographs (five standardized views) and self-taken photographs (three views) were captured. Two blinded, independent face-to-face physician PASI measures were recorded, with the first rater used as the primary reference value. Fitzpatrick Skin Type and Physician Global Assessment (PGA) were also noted. We trained our ‘MultiViT’ model over 300 epochs and tested using an 80:20 split of the participants. MultiViT advances beyond standard ViTs by handling multiple images and resolutions simultaneously. Mean absolute error (MAE) was used to assess prediction accuracy and compare the standard ViT models with the MultiViT. We captured 1109 images from 152 participants; 63% were male, median age of 45.5 years [interquartile range (IQR) 33.75–57.0], median body mass index of 29.68, 84% Fitzpatrick Skin Types I–IV, and 16% V and VI. The majority (76%) had mild-to-moderate disease (PGA ≤3); median PASI was 8.2 (IQR 5.7–12.7). The MultiViT model demonstrated an MAE of 3.88 for predicting PASI from skin images vs. 5.13 for the standard ViT. When stratified by skin type, I–IV performed better than V and VI (MAE of 2.80 and 8.17, respectively), and by disease severity, PGA ≤3 performed better than PGA &amp;gt;3 (MAE of 1.97 and 9.13, respectively). Our findings suggest the MultiViT model offers potential for automated psoriasis severity assessments from skin images, with favourable prediction accuracy despite a small dataset. An expanded and more diverse (Fitzpatrick Skin Type, severity) dataset will enable further refinement, validation and testing of the MultiViT model in trial and real-world settings. Future integration into a smartphone application will facilitate self-monitoring of psoriasis and healthcare efficiency for improved health and cost outcomes in psoriasis.
P117 Dose optimization of bimekizumab for adult patients with plaque psoriasis: an interim analysis of data from a real-world, multicentre, retrospective review
Journal: British Journal of Dermatology (2024)

Abstract The standard bimekizumab dosing regimen for adult patients with plaque psoriasis is 320 mg administered as a subcutaneous injection at Weeks 0, 4, 8, 12, and 16, then every 8 weeks (Q8W) thereafter. However, dose optimization may be required due to variability in treatment response. We conducted a real-world, multicentre, retrospective review of bimekizumab dose optimization for plaque psoriasis in adults. From a total cohort of 91 patients, we identified 15 (16.5%) that underwent dose optimization from Q8W to every 4 weeks (Q4W; 93.3%, 14/15) or every 6 weeks (Q6W; 6.7%, 1/15) in the maintenance period. All patients underwent dose optimization due to lack of efficacy. Mean age was 47.7 (range: 23–74) years, with 60% (9/15) being female. Mean time to dose optimization was 42.4 (range: 15.6–99) weeks. At the time of dose escalation (n = 15), mean psoriasis area and severity index (PASI) score was 3.4 (mean improvement from baseline: 50.5%) and mean body surface area (BSA) was 3.2% (mean improvement from baseline: 51%), with Investigator Global Assessment (IGA) scores of 1 (33.3%, 5/15), 2 (46.7%, 7/15), 3 (13.3%, 2/15), and 4 (6.7%, 1/15). Prior to dose escalation, there were 33.3% (5/15), 46.7% (7/15), and 20% (3/15) of IGA 0/1, 75% improvement in PASI (PASI75), and 90% improvement in PASI (PASI90) responders. Following a mean follow-up period of 17.5 (range: 2.9–35.6) weeks after dose optimization, there were 86.7% (13/15), 66.7% (10/15), 66.7% (10/15), and 60% (9/15) responders in IGA 0/1, PASI75, PASI90, and PASI100. From the time of dose escalation, mean improvement in PASI and BSA were 79.2% (85.2% from baseline) and 81.2% (90.6% from baseline), respectively. There was 1 (6.7%) discontinuation due to persistent lack of efficacy following dose optimization. Five treatment-related adverse events (AEs) occurred, including candidiasis (13.3%, 2/15), folliculitis (6.7%, 1/15), recurrent cellulitis (6.7%, 1/15), and recurrent urinary tract infection (UTI; 6.7%, 1/15). Of these, only the UTI patient (6.7%, 1/15) experienced an AE following dose escalation. There were no safety-related treatment discontinuations, nor any serious infections, suicidal ideation/behaviour, malignancies, hypersensitivity reactions, major adverse cardiac events, or hepatic abnormalities. In Phase III clinical trials, while IGA 0/1 and PASI90 rates were comparable between dosing regimens, Q4W maintenance dosing of bimekizumab was associated with a higher PASI100 rate than Q8W dosing [73.5–83% (Q4W) vs. 66–70.8% (Q8W)] at 1-year. Furthermore, AEs were comparable between dosing regimens with slightly higher rates of oral candidiasis and UTI with Q4W dosing. Our real-world results show increased achievement of IGA 0/1, PASI90, and PASI100 with dose optimization and no new safety signals. Study limitations include its small sample and retrospective nature.
FC29 Risk of developing psoriatic arthritis in patients with psoriasis initiating treatment with different classes of biologics
Journal: British Journal of Dermatology (2024)

Abstract It is debated whether this risk of psoriatic arthritis (PsA) is different according to the class of the biologic the patient with psoriasis (PsO) is receiving. To investigate the risk of PsA in patients receiving different classes of biologics. A retrospective observational study involving consecutive bio-naïve patients. The cumulative incidence rate of PsA using an event per person-years analysis was estimated in patients stratified according to the class of the biologic (TNF-a, IL-17 or IL-23 inhibitors). Cox proportional hazards models involving time-dependent explanatory variables were fitted to estimate the hazard risk (HR) of PsA. Six hundred and twenty-two patients, 388 (62.4%) males, mean age 46.9 years, were included. They have been treated with TNF-a (n = 317, 50.9%), IL-17 (n = 164, 26.4%) or IL-23 inhibitors (n = 141, 22.7%), and followed for 2820.2 person-year (a mean of 4.73 ± 2.12 years per person). Incidence rates of PsA were 2.60 [95% confidence interval (CI) 1.95–3.49], 1.58 (95% CI, 0.82–3.04) and 1.14 (95% CI, 0.51–2.54) cases per 100 patients/year in the TNF-a, IL-17 and IL-23 inhibitors groups, respectively. The variables associated with higher risk of incident PsA were baseline PASI score [adjusted hazard ratio, aHR 1.18 (95% CI 1.12–1.25) P &amp;lt; 0.001], family history of PsA [aHR 2.78 (95% CI 1.90–3.52), P = 0.005] and nail involvement [hazard ratio 1.85 (1.07–3.21) P = 0.029]. Treatment with IL-17 or IL-23 inhibitors was associated with a lower risk of PsA compared with TNF-a inhibitors [aHR 0.43 (95% CI 0.20–0.93) P = 0.031] and [aHR 0.58 (95% CI 0.24–0.75) P = 0.015], respectively. Treatment with IL-17 or IL-23 inhibitors is associated with lower risk of PsA.
P115 Real-world experience of bimekizumab for plaque psoriasis in adult patients with prior exposure to interleukin-23 inhibitors: a 52-week multicentre retrospective review
Journal: British Journal of Dermatology (2024)

Abstract For adult patients with plaque psoriasis, limited information exists on switching between classes from an IL-23 inhibitor (IL-23i) to bimekizumab. We conducted a real-world, multicentre, retrospective study of bimekizumab following IL-23i exposure. Twenty-three subjects with prior exposure to an IL-23i were identified. Effectiveness outcomes included Investigator Global Assessment (IGA), psoriasis area and severity index (PASI), body surface area (BSA), and IGA × BSA scores. Safety was assessed via treatment-related adverse events (AEs). For 23 patients included, the mean age was 43 (range: 20–73) years, with 56.5% (13/23) being male. Prior IL-23i exposures included guselkumab only (52.2%, 12/23), risankizumab only (21.7%, 5/23), and both guselkumab and risankizumab (26.1%, 6/23). Reasons for discontinuation included lack of efficacy (95.7%, 22/23) and persistent psoriatic arthritis (4.3%, 1/23). Primary non-response to prior IL-23i was defined as lack of IGA 0/1 and/or 75% improvement in PASI (PASI75) at Week 16, whereas secondary non-response to prior IL-17i was defined as loss of IGA 0/1 and/or PASI75 response at any point afterwards. At Weeks 52 ± 6: IGA 0/1 was achieved by 66.7% (12/18); mean PASI, BSA, and IGA × BSA improvements from baseline were 69.6% (8.5–0.8), 71.8% (8.2–0.7%), and 74.6% (22.6–1.4), respectively; 65.2% (15/23), 56.5% (13/23), and 47.8% (11/23) achieved PASI75, 90% improvement in PASI (PASI90), and 100% improvement in PASI (PASI100), respectively; 78.3% (18/23), 69.6% (16/23), and 65.2% (14/23) achieved absolute PASI scores &amp;lt;3, &amp;lt;2, and &amp;lt;1; and 73.9% (17/23) achieved BSA &amp;lt;1%. In prior IL-23i primary non-responders (n = 6), 83.3% (5/6) achieved IGA 0/1 and/or PASI90 and 50% (3/6) achieved PASI100 with bimekizumab at Week 52 ± 6. In prior IL-23i secondary non-responders (n = 12), 66.7% (8/12) achieved IGA 0/1 and/or PASI90 and 50% (6/12) achieved PASI100 with bimekizumab at Week 52 ± 6. Four treatment-related AEs occurred (17.4%, 4/23), including oral candidiasis (8.7%, 2/23) and bacterial folliculitis (4.3%, 1/23). There were 3 (13%) treatment-related discontinuations [lack of efficacy (n = 2); AE: anxiety (n = 1)]. While our real-world results of patients with prior IL-23i exposure demonstrated lower achievement of effectiveness endpoints (IGA 0/1: 66.7%; PASI90: 56.5%; PASI100: 47.8%) at Week 52 ± 6 as compared with clinical trials, the discrepancy between clinical trials and this study may be explained by a more difficult-to-treat population with multiple biologic failures (56.5% utilized &amp;gt;3 biologics and 26.1% used several IL-23i). Our real-world study also included patients with &amp;gt;1 biologic failure, while Phase III clinical trials excluded this population. Our results highlight the long-term utility of bimekizumab in the setting of prior IL-23i exposure. Study limitations include its small sample and retrospective nature.
P62 Efficacy and safety of picankibart in moderate-to-severe plaque psoriasis: a randomized, double-blind, Phase 3 CLEAR-1 trial
Journal: British Journal of Dermatology (2024)

Abstract The aim of this study was to evaluate the efficacy and safety of picankibart (an inhibitor of the interleukin-23 p19 subunit) compared with placebo in patients with moderate-to-severe plaque psoriasis. CLEAR-1 was a Phase 3, randomized, double-blind, placebo-controlled trial. Eligible patients between 18 and 75 years old who had a diagnosis of moderate-to-severe plaque psoriasis for at least 6 months [body surface area involvement ≥10%, psoriasis area and severity index (PASI) ≥12, and static Physician’s Global Assessment (sPGA) ≥3] at screening and baseline visits were randomly assigned at a 2:2:1 ratio to receive 200 mg picankibart at Week 0, 4, and 8 followed by 200 mg picankibart every 12 weeks at Week 20, 32, and 44; 200 mg picankibart at Week 0, 4, and 8 followed by 100 mg picankibart every 12 weeks at Weeks 20, 32, and 44; or placebo at Weeks 0, 4, and 8 followed by 200 mg picankibart at Weeks 16, 20, 24, 32, and 44. Co-primary endpoints were the proportions of patients achieving ≥90% improvement from baseline in PASI (PASI 90) and a sPGA score of 0 or 1 at Week 16 (superiority comparison of picankibart 200 mg with placebo) assessed in the intention-to-treat population. A total of 500 patients were randomly assigned to receive 200 mg picankibart through Week 52 (n = 199), 200 mg picnakibart for 16 weeks followed by 100 mg from Week 16 to Week 52 (n = 202), or placebo followed by 200 mg picankibart (n = 99). The mean age of patients was 41.9 years (standard deviation 12.0), 384 (76.8%) were men; baseline characteristics were balanced across treatment groups. Co-primary endpoints were met. At Week 16, PASI 90 was achieved by 322 (80.3%) patients receiving picankibart vs. 2 (2.0%) receiving placebo [difference 78.3% (95% confidence interval (CI) 73.5–83.1%); P &amp;lt; 0.0001], and sPGA 0 or 1 was achieved by 375 (93.5%) patients receiving picankibart vs. 13 (13.1%) receiving placebo [difference 80.4% (95% CI 73.4–87.5%); P &amp;lt; 0.0001]. Picankibart also showed superiority to placebo regarding all key secondary endpoints (P &amp;lt; 0.0001). The improvements were maintained at Week 52 for patients receiving 200 mg or 100 mg picankibart. The rate of treatment-emergent adverse events was similar between picankibart and placebo groups. No new safety signal was noted during the maintenance period. Picankibart showed superior efficacy to placebo in the treatment of moderate-to-severe plaque psoriasis. The safety profile of picankibart was favourable with no unexpected safety findings.
P23 Epidermal feed-forward inflammatory loop in psoriasis plays a dominant role in psoriasis development
Journal: British Journal of Dermatology (2024)

Abstract Skin is the outmost barrier that separates the human body from the external environment. In psoriasis, immune cells are resident and/or infiltrated into the epidermis in order to form the epidermal immunological microenvironment (EIME) and constitute a complex interaction with keratinocytes, together with nerve and microbiota influence. Our results have shown that psoriasis is mainly mediated by a specific inflammatory environment composed by keratinocyte-neuro-immune cell units (KNICUs), which is the interaction of activated epidermal immune cells, keratinocytes and peripheral nerve fibres, which are increased in psoriatic lesions and are closely innervated around immune cells and keratinocytes. We mapped psoriatic skin immune cells from a paired lesion, a perilesion, and a nonlesion using mass cytometry. Phenotypical dendritic cells (DCs) were found in the psoriatic epidermis and dermis. Psoriatic dermal CD1c+CD11b+ cDC2s migrated to the epidermis in the perilesional skin, positioned in preinitiation. CD1c+CD11b+ cDC2s rapidly replaced EpCAM+CD11clowLC cells and initiated inflammation. Simultaneously, CD207+CD11chiLC and CD5+ T cells occurred in the psoriatic epidermis and orchestrated epidermal inflammation in psoriasis. Multiple units gather to complete circulatory and amplified loop, both an epidermal feed-forward inflammatory loop constituted with epidermal dendritic cells pDC, cDC, Langerhans cells and CD8+T cells. The epidermal loop was more significant and coincided with the inflammation of psoriasis.