tbuckley/cabot-search huggingface dataset:
P25 Genome-wide association study and predictive models for the efficacy and safety of NB-UVB phototherapy in psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Background Psoriasis is a chronic inflammatory skin disease affecting ∼125 million individuals worldwide. Although the treatment of psoriasis has entered an era of biological agents and small molecule drugs, narrowband ultraviolet B (NB-UVB) phototherapy still represents an effective, cost-efficient, and safe therapeutic option for patients with plaque psoriasis. However, the clinical and genetic predictors of NB-UVB treatment response remain limited. Objective We aimed to detect single nucleotide polymorphisms (SNPs) associated with the efficacy of NB-UVB in treating psoriasis and its adverse events (AEs), in order to establish predictive models for the efficacy and safety of NB-UVB phototherapy. Methods A total of 252 patients with moderate-to-severe plaque psoriasis were enrolled in this study and underwent 12 weeks of NB-UVB phototherapy. Psoriasis area and severity index (PASI) and the AEs of NB-UVB treatment were recorded during follow-up. Whole blood samples were collected from the participants, and extracted DNA was genotyped using Infinium Global Screening Array-24 v3.0 BeadChip. Genome-wide association studies (GWASs) were performed to identify SNPs related to NB-UVB treatment response. Predictive models for the efficacy and safety of NB-UVB therapy, which involved SNPs along with clinical parameters, were developed utilizing logistic regression and further validated by receiver operating characteristic (ROC) curve and calibration curve. Results After 4 weeks of NB-UVB phototherapy, 40.8% of patients achieved PASI50. Through GWASs, we discovered that SLC7A13 rs35314286 TA allele [odds ratio (OR) = 2.631, P = 5.96 × 10−6] and DYNC1H1 rs941636 A allele (OR = 3.066, P = 3.15 × 10−6) were significantly correlated with better efficacy of 4-week NB-UVB treatment. After 12 weeks of treatment, 61.4% of patients achieved PASI75. Seven ATP2B2 SNPs and 11 PSMB7 SNPs significantly impacted 12-week PASI75 achievement. During the treatment, 29.8% of patients experienced AEs that included pruritus, sting, numbness, erythema, vesicles, desquamation, hyperpigmentation, and photosensitivity. Two KCNA2 SNPs, seven THSD7B SNPs and one TENM4 SNP were considerably associated with the occurrence of AEs. Based on the clinical parameters (body mass index, smoking history, PASI score, and the percentage of PASI improvement at Week 4) and NB-UVB relevant SNPs, predictive models for the efficacy and safety of NB-UVB phototherapy were established, demonstrating excellent predictive capacities with area under the curve (AUC) value being 0.81 for 4-week efficacy, 0.80 for 12-week efficacy, and 0.85 for AE development. Conclusion Multiple gene SNPs were identified to be correlated with the efficacy and safety of NB-UVB phototherapy. Moreover, predictive models of NB-UVB treatment response were subsequently established. Our findings might contribute to the advancement of precision phototherapy in psoriasis. Clinical trial registration (www.chictr.org.cn), identifier (ChiCTR2000036186).
P41 Phase 2b, long-term extension, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER-2
Journal: British Journal of Dermatology (2024)

Abstract JNJ-77242113, a targeted oral peptide, inhibits interleukin (IL)-23 signalling by binding the IL-23 receptor. At all doses, JNJ-77242113 showed superior efficacy at Week (W)16 vs. placebo in moderate-to-severe psoriasis in FRONTIER-1. FRONTIER-2 was a multicentre, long-term extension, double-blind, dose-ranging, Phase 2b study evaluating efficacy and safety of JNJ-77242113 in adults with moderate-to-severe plaque psoriasis who were candidates for systemic treatment or phototherapy. FRONTIER-1 randomized patients 1:1:1:1:1:1 to JNJ-77242113 25 mg daily (QD), 25 mg twice daily (BID), 50 mg QD, 100 mg QD, 100 mg BID, or placebo through W16. In FRONTIER-2, patients completing FRONTIER-1 (at W16) continued their assigned dose through W52; those randomized to placebo crossed over to 100 mg QD (PBO→100 mg QD). The primary endpoint was the proportion of patients achieving ≥75% improvement in psoriasis area and severity index (PASI75) at W52. Response rates were estimated using non-responder imputation and FRONTIER-1 baseline data. Response rates among JNJ-77242113–treated patients from FRONTIER-1 were maintained, across dose groups, through W52. Patients who crossed over to JNJ-77242113 from placebo at W16 (PBO→100 mg QD) had substantially higher response rates at W52. At W52, proportions of patients achieving PASI75 with JNJ-77242113 were: 25 mg QD 48.8%, 25 mg BID 58.5%, 50 mg QD 69.8%, 100 mg QD 65.1%, 100 mg BID 76.2%; PBO→100 mg QD 65.7%; the respective PASI90/PASI100 rates were 27.9%/14.0%, 36.6%/17.1%, 41.9%/20.9%, 51.2%/25.6%, 64.3%/40.5%, 57.1%/34.3%. Proportions of patients achieving an Investigator’s Global Assessment (IGA) score of 0/1 or 0 with JNJ-77242113 at Week 52 were: 25 mg QD 37.2%/14.0%, 25 mg BID 46.3%/19.5%, 50 mg QD 60.5%/23.3%, 100 mg QD 60.5%/30.2%, 100 mg BID 73.8%/42.9%, and PBO→100 mg QD 65.7%/31.4%. Approximately 90% of patients receiving JNJ-77242113 100 mg BID who had achieved a PASI75, PASI90, or IGA 0/1 response at W16 maintained the response at W52. Across dose groups, 58.6% of patients experienced adverse events (AEs), with no evidence of a dose-dependent increase in AEs, including gastrointestinal disorders. The proportion of patients with serious AEs through W52 was 4%; all serious AEs were considered unrelated to study treatment. In patients with psoriasis receiving JNJ-77242113, the first targeted oral peptide to selectively block IL-23 pathway signalling, rates of near-complete/complete skin clearance from FRONTIER-1 were maintained through W52; the highest response rates were seen in patients randomized to JNJ-77242113 100 mg BID. Among patients who had achieved a PASI or IGA response at W16, responses were maintained in substantial proportions of patients at W52. Consistent with prior studies, no safety signals were identified.
P60 Safe application of Guselkumab in a psoriasis patient combined with coronary heart disease after percutaneous coronary intervention for acute myocardial infarction
Journal: British Journal of Dermatology (2024)

Abstract Aim Recent studies indicated psoriasis leads to an increase of inflammatory cytokine levels in the skin lesions, the resulting asymptomatic chronic subclinical inflammation can also progress to a variety of complications, including cardiovascular diseases, arthritis, metabolic syndrome, inflammatory bowel disease and so on. Patients combined with acute myocardial infarction (MI) need to be treated by percutaneous coronary intervention (PCI); there is a lack of evidence indicating how to select a safe biologic after PCI. Methods Here, we report a long disease duration psoriasis patient who underwent PCI and then treated with Guselkumab, maybe can bring some experience for the treatment of a similar situation. A 49-year-old male came to our department with severe plaque psoriasis [psoriasis area and severity index (PASI) 15.2, body surface area (BSA) 12%, sPGA 4] in August 2022. The first plaque of psoriasis appeared 25 years ago and did not relapse after treatment with traditional drugs. He was diagnosed with hypertension in March 2011 but did not receive formal treatment. Results On 14 February 2021, the patient experienced a burst of acute MI and was treated with PCI. It was learned that the patient had a history of hypertension for 10 years and a history of psoriasis for 25 years. After discharge, he regularly returned to the outpatient departments of cardiology and rheumatology for follow-up visits, and his current physical condition remains good. In August 2022, he came to our department with a relapse of skin lesion. According to suggestions provided by multiple disciplinary team, for the treatment of psoriasis, he was treated with Guselkumab with recommended dosage (subcutaneous 100 mg at Weeks 0, 4 and then every 8 weeks) in our department after routine screenings of blood tests and chest CT before biologic treatment. After two injections of 100 mg Guselkumab, he achieved 100% percentage improvement of skin lesions (PASI 0, BSA 0%, sPGA 0) at Week 12, which significantly improved his quality of life. After 12-month follow-up, the patient did not appear any abnormality of examination for cardiovascular disease. Also, the skin lesion of psoriasis was controlled well without relapse or exacerbation. No safety issues appeared during the follow-up too. Conclusion We first report a long-term plaque psoriasis patient combined with hypertension and cardiovascular disease and treated with Guselkumab after PCI. Application of Guselkumab after PCI was proved to be safe and maintain stable skin lesion clearance efficacy.
P73 Fatty acid rewiring via PPARα-FADS2 axis in keratinocytes contributes to skin inflammation in psoriasis through NF-κB pathway
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, accompanied by significant alterations in immune homeostasis. Dysregulation of fatty acid metabolism, particularly involving polyunsaturated fatty acids (PUFAs), has been implicated in the pathogenesis of psoriasis; however, the precise relationship between metabolic dysregulation and inflammatory responses in psoriasis remains poorly understood. In this study, we investigated the role of Δ6 desaturase/fatty acid desaturase 2 (FADS2), the first and rate-limiting enzyme in PUFA synthesis, in psoriasis and its underlying mechanisms. We first demonstrate that the expression of FADS2 was significantly decreased in the epidermis of the skin lesions from psoriasis patients and imiquimod (IMQ)-induced psoriasis mouse model. Treatment with IL-23 inhibitor Guselkumab restored FADS2 expression in the epidermis of lesional skin of psoriasis patients. Furthermore, silencing FADS2 in cultured human keratinocytes resulted in the upregulation of multiple chemokines and antimicrobial peptides under M5 condition (a psoriasis-like inflammatory condition). Mechanically, suppression of FADS2 disrupted PUFA metabolism with an inhibition of the desaturation of omega-3 fatty acids to the anti-inflammatory metabolite docosahexaenoic acid (DHA), thereby contributing to the inflammatory processes through the NF-κB pathway. Additionally, we found that FADS2 expression in keratinocytes was dependent on peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor involved in lipid metabolism across various tissues. A reduction in the PPARα-FADS2 axis was observed in the lesional skin of psoriasis patients and IMQ-induced psoriasis mouse model. In vivo experiments revealed that silencing FADS2 via the topical application of small interfering RNA (siRNA) exacerbated IMQ-induced psoriasis-like dermatitis, whereas enhancing FADS2 expression through PPARα activation with its agonist WY14643 led to a significant attenuation of psoriasis inflammation. These findings identify PPARα as a critical regulator of FADS2 expression in psoriasis and elucidate the contribution of FADS2 to fatty acid reprogramming and inflammatory responses in psoriasis. Therefore, FADS2 and PPARα emerge as promising therapeutic targets for managing psoriasis.
P21 Development of a novel multidisciplinary care model for screening and managing patients with psoriatic arthritis: consensus guidance for primary care providers in Canada
Journal: British Journal of Dermatology (2024)

Abstract There is an unmet need for timely assessment and diagnosis of psoriatic arthritis (PsA) in patients with psoriasis (PsO) and a lack of standardized clinical guidance for primary care providers (PCPs) for supporting the screening and management of these patients. Our study aimed to develop consensus guidance for screening and managing PsA in patients diagnosed with PsO, and identify potential roles for pharmacists within the multidisciplinary care team to facilitate timely specialist access. We used a modified DELPHI process to gather insights on screening practices, quality of life (QoL) monitoring, and lifestyle counselling from 11 Key Opinion Leaders across Canada, including pharmacists, rheumatologists, and dermatologists. Key questions that address current care gaps within each category were identified, and the extent of agreement was determined through two rounds of voting. The threshold for designating consensus for each question was ≥75% agreement. After two rounds of voting, the following recommendations for the multidisciplinary screening and management of PsA in patients with PsO were identified: (i) screening for PsA should be performed by dermatologists or family physicians; (ii) all patients diagnosed with PsO should be screened every 6–12 months; (iii) screening should rely on clinical judgement with a focus on swollen and tender joints, though validated screening tools can be used in the absence of adequate clinical judgement, which can be administered via virtual/telephone appointments; (iv) patients flagged through virtual screening should have an in-person follow-up assessment with their PCP or dermatologist, followed by referral to a rheumatologist if deemed necessary; (v) dermatologists and rheumatologists should be responsible for monitoring QoL in patients with PsO and PsA, respectively, with the method of assessment at the discretion of the responsible HCP; (vi) pharmacists are best positioned to review adherence to biologic therapy at each medication refill, manage injection site reactions, monitor drug safety, and assist with navigating reimbursement; and (vii) pharmacists should counsel patients on health and lifestyle factors such as smoking, alcohol consumption, and maintaining healthy body weight, advise patients on all appropriate vaccines, and counsel patients on the importance of staying up to date on vaccinations. This consensus-derived guidance provides a valuable and novel framework for the multidisciplinary management of PsA in Canada, with pharmacists being uniquely positioned to help address some of the current gaps in care. Implementing these best practices has the potential to reduce delays in diagnosing and initiating treatment for PsA in patients with PsO and improve overall patient ­outcomes.
P59 Clinic and genetic characteristics of patients with generalized pustular psoriasis: a bidirectional cohort study
Journal: British Journal of Dermatology (2024)

Abstract Generalized pustular psoriasis (GPP) is an infrequent disease with significant genetic predisposition, the IL36RN gene has been evidenced of pathogenicity, additionally, furthermore, eight genes including CARD14, AP1S3, MPO, SERPINA1, SERPINA3, BTN3A3, TNIP1 and TGFBR2 have been successively identified of involved in the pathogenesis of GPP.1,2 However, a considerable proportion of quintessential GPP patients either exhibit no mutations in the aforementioned genes, or been detected of only single-allele heterozygous variation, or have found two or more pathogenic genes. The prevailing view thought GPP follows an oligogenic inheritance pattern rather than a monogenic one. Currently, genetic testing for GPP employs methodologies such as whole-exome sequencing, next-generation sequencing (NGS) targeted gene panel exome sequencing and Sanger sequencing for specific genes like IL36RN. However, the aforementioned methods do not address the identification of unknown genes, variations in non-coding regions, structural variants (SVs), or copy number variations (CNVs). Whole-genome sequencing (WGS), by comparing individual genomic sequences to a reference genome, provides detailed information on single nucleotide variations (SNVs), insertions and deletions (InDels), SVs and CNVs within the genome. The application of WGS to the research of GPP will undoubtedly contribute to the investigation of its unknown mechanisms. In our study, WGS was carried out on a total of 79 patients diagnosed with pustular psoriasis (PP) up to the present, comprising single GPP (35), psoriasis vulgaris (PsV)-GPP (15), and palmoplantar pustulosis (PPP) or acrodermatitis continua (ACH)-GPP (4), single PPP (10) or ACH (2), clinic characteristics including groove or map-like tongue, nail involvements were also recorded for phenotypic matching. Four variant types (c.115+6T&amp;gt;C, c.334G&amp;gt;A, c.227C&amp;gt;T and c.169G&amp;gt;A) of IL36RN in 43 patients (43/79) were identified, among which c.115 + 6T&amp;gt;C exhibited the highest frequency. Among them, 19 patients had c.115 + 6T&amp;gt;C homozygous mutations, 15 patients had c.115 + 6T&amp;gt;C single heterozygous mutation and 2 patients had c.115 + 6T&amp;gt;C and c.227C&amp;gt;T complex heterozygous mutations. A total of 21/43 patients had IL36RN biallelic mutations, and 22/43 patients had IL36RN monoallelic mutations. In addition, some predicted pathogenic mutations were detected in TNIP1, SERPINA1, MPO, TGFBR2, AP1S3 and CARD14 genes.
P27 The state of the skin microbiome in patients with psoriasis
Journal: British Journal of Dermatology (2024)

Abstract In dermatological practice, in the pathogenesis of chronic dermatoses, much attention is paid to the state of the skin microbiome. According to research, the role of superantigens—protein substances—bacterial toxins of staphylococcal, streptococcal nature, as well as fungi of the genus Candida, takes place in the pathogenesis of psoriasis. The purpose of our research was to assess the state of the skin microbiome in patients with psoriasis. Research materials and methods We examined 94 patients with psoriasis aged 12–69 years who received inpatient treatment at the Dermatological Department of the Research Dermatology Centre of Clinic of the Ministry of Health of the Republic of Uzbekistan. Taking into account gender, 40 patients were male and 54 were female. Clinical, biochemical, microbiological and statistical studies were conducted in all patients. The control group consisted of 72 healthy individuals of the appropriate age. The results of the study Microbiological studies of the skin in patients with psoriasis have shown a high detectability of opportunistic microorganisms of the Micrococaccea family—staphylococcus spp., which amounted to 62.7% of cases. Taking into account the clinical course of dermatosis, frequent seeding of opportunistic microflora was noted in the progressive stage—72.8%, whereas in the stationary stage—27.1%, respectively. According to the species identification of staphylococci in the examined patients, Staphylococcus epidermidis was most often sown—S. epidermidis was most often sown—32.2% and Staphylococcus haemoliticus—27.1%, Staphylococcus aureus—23.7% of cases. Cases with increased colonization caused the development of the syndrome of colonization resistance of opportunistic microorganisms. Conclusion Thus, the results obtained indicate that the role of opportunistic microorganisms in the clinical course of psoriasis is of clinical importance, the degree of colonization plays an important role in the pathogenesis of psoriasis, causing the development of the syndrome of colonization resistance of opportunistic microorganisms on the skin of patients.
P34 The incidence and prevalence of psoriasis in Newfoundland and Labrador, Canada
Journal: British Journal of Dermatology (2024)

Abstract The Canadian province of Newfoundland and Labrador (NL) is recognized as a founder population of English and Irish descent, with an approximate population of 525 000 people. The incidence and prevalence of psoriasis in the NL population have not been formally studied, although provincial dermatologists acknowledge an increased burden of psoriasis, compared with other regions in Canada. Our objective was to examine the incidence and prevalence of psoriasis in NL and the variation by age, gender, geographic region, and time. Digital Health, Newfoundland and Labrador Health Services provided Provincial Electronic Health Records that were used to identify patients with psoriasis using International Classification of Diseases 9th revision (ICD-9) code 696 from 2001 to 2020. The prevalence of psoriasis was 6830 per 100 000 people (3801 women, 3029 men), and incidence was 365.4 per 100 000 person-years [95% confidence interval (CI), 298.0–432.9]; 395.9 (329.5–462.2) per 100 000 person-years for women and 334.2 (263.5–404.9) per 100 000 person-years for men. The peak age group for incident cases was 55–59 years, suggesting that the late onset of psoriasis is higher than in most Western European and North American populations. There was significant geographic variation in the prevalence of psoriasis, as 20 of the 234 communities with a population over 200 people had a psoriasis prevalence between 0 and 3% and nine communities with psoriasis prevalence over 30%. It is likely that regional founder effects most likely account for the high prevalence of psoriasis in selected communities, although environmental influences cannot be discounted. The NL populations had a high incidence and prevalence of psoriasis, with significant regional variations in prevalence.
P66 Perforating dermatosis in a young female patient receiving adalimumab biosimilar CTP-17 for chronic plaque psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Opportunistic infections, reactivation of latent tuberculosis, demyelinating diseases were found to be the most severe adverse events associated with adalimumab. Among TNF-a inhibitors-related cutaneous adverse reactions, paradoxical reactions are the most common, whereas sweet-like neutrophilic dermatosis or perforating dermatosis have been rarely reported. A 34-year-old Caucasian woman was referred to the outpatient clinic of the University Hospital of Verona for acute onset of diffuse erythematous plaques with concentric hyperkeratosis and ulceration localized on the right thigh, right glutaeal area and elbows bilaterally, associated with pain and difficulties in walking. The acute skin reaction occurred 3 days after the switching to adalimumab biosimilar CTP17. In particular, the patient affected by chronic plaque psoriasis and psoriatic arthritis had been successfully treated with adalimumab biosimilar GP2017 for 2 years, which was later switched to CTP17 for non-medical reasons. The patient did not report any comorbidities or known allergies and was not taking other medications apart from the adalimumab biosimilar. No other symptoms were reported. The skin lesions were biopsied, and the histological examination revealed areas of epidermal ulceration, overlaid by dendritic-granulocytic crust associated with transepidermal elimination of elastic fibres (elastin). Dermal infiltrate with a rich plasma cellular component was also present. The histological diagnosis was consistent with acquired perforating dermatosis. Fungal, bacterial and mycobacterial cultures were negative. Consequently, adalimumab biosimilar CTP17 was suspended and a 30-day course of systemic therapy with corticosteroids was prescribed. After ∼60 days the cutaneous lesions progressively improved, and the ulcers have been re-epithelized, with a residual post-inflammatory erythema. Perforating dermatosis is usually associated with conditions such as trauma, diabetes, chronic renal failure and lymphoma, but is occasionally also triggered by drugs including biologics such as adalimumab, infliximab, etanercept and risankizumab.