Response Types and Factors Associated with Response Types to Biologic Therapies in Patients with Moderate-to-Severe Plaque Psoriasis from Two Randomized Clinical Trials.

INTRODUCTION: This study aimed to understand treatment response dynamics, including factors associated with favorable response, among patients with moderate-to-severe psoriasis who received guselkumab, adalimumab, or secukinumab. METHODS: These post hoc analyses used data from the phase III clinical trials ECLIPSE and VOYAGE 1, which were conducted between September 2021 and November 2022. On the basis of absolute Psoriasis Area and Severity Index (aPASI) scores, patients were divided into short-term response types (SRT1-6, based on week 20-48 response) and long-term response types (LRT1-4, based on week 52-252 response). Response types (RTs) were based on aPASI cutoffs deemed clinically relevant by the investigators; SRT1/LRT1 were the most favorable response types. Baseline characteristics were compared across RTs, and logistic regression analyses established factors associated with SRT1/LRT1. RESULTS: Overall, 1045, 662, and 272 patients were included in the ECLIPSE short-term, VOYAGE 1 short-term, and VOYAGE 1 long-term analyses, respectively. Mean age, body mass index (BMI), baseline aPASI score, and body surface area were lower in SRT1 than SRT6. In VOYAGE 1, adalimumab treatment, high BMI, and current/former smoking status resulted in less favorable responses. In the VOYAGE 1 long-term analysis, patients in LRT4 had the highest baseline aPASI score, were older, and were more often obese compared with other LRT groups. Regression analyses showed that SRT1 (both treatments) in VOYAGE 1 and ECLIPSE, and LRT1 (guselkumab group) in the VOYAGE 1 long-term analysis, were associated with week 16 aPASI response. In VOYAGE 1, SRT1 was associated with psoriasis duration and smoking status. CONCLUSIONS: Early treatment response and baseline characteristics, including smoking, psoriasis duration, and obesity, may be associated with longer-term response to biologics. TRIAL REGISTRATION NUMBERS: ECLIPSE: NCT03090100, VOYAGE 1: NCT02207231.

Guselkumab in Patients with Scalp Psoriasis: A post hoc Analysis of the VOYAGE 2 Phase III Randomized Clinical Trial.

Scalp psoriasis affects approximately 80% of patients with psoriasis and can negatively impact their quality of life. This post hoc analysis of the VOYAGE 2 Phase III randomized clinical trial evaluated scalp response to guselkumab treatment and its association with skin response and patient-reported outcomes. The study included patients with moderate-to-severe plaque psoriasis and baseline scalp psoriasis who were initially randomized to receive guselkumab. Patients were divided into 3 groups based on their achievement of a Psoriasis Area and Severity Index 90 response at week 28: responder continuation, non-responder continuation and responder withdrawal. In all 3 groups, mean Psoriasis Area and Severity Index head and scalp-specific Investigator's Global Assessment scores improved through week 28. In the responder withdrawal group, these scores worsened after treatment withdrawal at week 28, but remained stable through week 48 in both continuation groups. Trends in Dermatology Life Quality Index and Psoriasis Symptoms and Signs Diary itch scores mirrored those of mean scalp-specific Investigator's Global Assessment scores through week 48. Within-subject correlations were 0.83 between scalp-specific Investigator's Global Assessment and Psoriasis Area and Severity Index head scores and 0.78 between scalp-specific Investigator's Global Assessment and Psoriasis Symptoms and Signs Diary itch scores. Through week 252, Psoriasis Area and Severity Index head scores remained stable in the responder continuation group, improved in the non-responder continuation group and rapidly improved by week 84 in the responder withdrawal group after retreatment.

Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥ 156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

BACKGROUND: Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. MATERIALS AND METHODS: This post-hoc analysis of the 5-year VOYAGE 1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥ 156 consecutive weeks (PASI = 0 group) with those that never achieve PASI = 0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. RESULTS: Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥ 156 consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p < 0.05) associated with the PASI = 0 group. CONCLUSION: A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥ 156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. TRIAL REGISTRATION: NCT02207231.

Nail psoriasis dynamics during biologic treatment and withdrawal in patients with psoriasis who may be at high risk of developing psoriatic arthritis: a post hoc analysis of the VOYAGE 2 randomized trial.

BACKGROUND: Nail psoriasis is a common, physiologically, and psychologically disruptive, and yet often under-treated manifestation of psoriasis. The objectives of this analysis were to investigate the trajectory of nail psoriasis, a risk factor for psoriatic arthritis (PsA), with guselkumab vs adalimumab treatment followed by withdrawal, and determine characteristics associated with nail response in patients treated with guselkumab. METHODS: This post hoc analysis of the phase III trial VOYAGE 2 included patients with moderate-to-severe plaque psoriasis and baseline nail involvement. Nail Psoriasis Severity Index (NAPSI) and Psoriasis Area and Severity Index (PASI) were analyzed through week 48 in patients randomized to guselkumab or adalimumab. Multiple logistic regression analyzed factors associated with NAPSI 0/1 at week 24/week 48 following guselkumab treatment. In a separate analysis, patients were stratified by prior biologic experience. RESULTS: Overall, 272 vs 132 patients receiving guselkumab vs adalimumab had nail psoriasis at baseline. Lower baseline NAPSI and week 16 PASI were associated with achieving NAPSI 0/1 at week 24 (NAPSI, odds ratio 0.685 [95% confidence interval: 0.586, 0.802]; week 16 PASI, 0.469 [0.281, 0.782]) and week 48 (NAPSI, 0.784 [0.674, 0.914]; week 16 PASI, 0.557 [0.331, 0.937]) with guselkumab. Previous biologic experience did not impact NAPSI response. Following treatment withdrawal at week 28, mean NAPSI was maintained in the guselkumab arm (week 24 1.7, week 48 1.9) and increased slightly in the adalimumab arm (week 24 1.4, week 48 2.3). Mean PASI increased across both treatment arms. CONCLUSIONS: Higher skin efficacy at week 16 was associated with better nail responses during guselkumab treatment. Nail psoriasis improvements reflected skin improvements. Following guselkumab withdrawal, nail response was maintained longer than skin response. Future studies should investigate whether such improvements in nail response reduce patients' risk of later PsA development. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02207244. Registered July 31, 2014.

Impact of psoriatic arthritis and comorbidities on ustekinumab outcomes in psoriasis: a retrospective, observational BADBIR cohort study.

OBJECTIVES: Psoriasis and psoriatic arthritis (PsA) are independently associated with comorbidities, including obesity and metabolic syndrome, which may impact treatment outcomes. This study aimed to assess baseline differences between patients with plaque psoriasis alone and those with concomitant PsA, and to investigate the impact of these characteristics on ustekinumab (UST) persistence and outcomes. METHODS: 9057 patients receiving UST or conventional systemic disease-modifying antirheumatic drugs were selected from the British Association of Dermatologists Biologic and Immunomodulators Register. The psoriasis and PsA cohorts were compared at baseline. Time to discontinuation during 10-year follow-up was assessed using multivariable Cox regression and Kaplan-Meier analyses, stratifying for interacting covariates and PsA status. Generalised linear mixed models assessed the impact of baseline characteristics on Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index over time. RESULTS: Greater comorbidity burden, including hypertension, diabetes, obesity and depression, and greater inability to work were observed in the PsA cohort than in the psoriasis cohort. PsA (HR 1.98), female sex (HR for male sex 0.72) and depression (HR 1.21) were associated with shorter UST persistence. PsA showed a differential association with UST persistence by PASI strata and prior biologic exposure. Quality of life was negatively impacted by depression and PsA. CONCLUSIONS: The negative impact of comorbidities on treatment persistence identified in this study emphasises the need for patient-centric, multidisciplinary care in screening for and managing comorbidities in psoriasis and PsA treatment. Psychological support and lifestyle management of modifiable risk factors, including obesity, should be considered.

Minimally invasive vertical versus conventional tooth extraction: An interrupted time series study.

BACKGROUND: Minimally invasive vertical tooth extraction techniques have evolved in light of the limitations of conventional tooth extraction techniques and flap surgery in preserving the alveolar bone. The authors conducted a study to obtain data on the performance of a vertical extraction system. This included comparing the need for flap surgery using the vertical extraction system versus conventional tooth extraction techniques for the extraction of anterior teeth and premolars not suitable for forceps extraction. METHODS: The authors conducted a prospective observational clinical study of the vertical extraction system versus conventional tooth extraction techniques using an interrupted time series in line with the Idea, Development, Exploration, Assessment, Long-term Follow-up collaboration framework for surgical innovation. RESULTS: Overall, 276 of 323 teeth (85.4%) in 240 patients were successfully extracted using the vertical extraction system. Of the 47 failures in the vertical tooth extraction cohort, 18 required flap surgery, resulting in an overall incidence of flap surgery of 5.6% (95% confidence interval [CI], 3.2% to 8.7%). During the routine care period, of the 94 anterior teeth and premolars in 78 patients, 21 teeth could not be extracted using conventional techniques and required flap surgery, leading to an incidence of flap surgery of 22% (95% CI, 14% to 32%). CONCLUSIONS: The results suggest that the vertical extraction system may be used with a high success rate for extraction of severely destroyed teeth, and its use may lead to a marked reduction in the need for flap surgery. Randomized clinical trials are needed to confirm the findings. PRACTICAL IMPLICATIONS: The use of a vertical extraction system may lower the incidence of flap surgery.

Perioperative supplementation with a fruit and vegetable juice powder concentrate and postsurgical morbidity: A double-blind, randomised, placebo-controlled clinical trial.

BACKGROUND & AIMS: Surgical trauma leads to an inflammatory response that causes surgical morbidity. Reduced antioxidant micronutrient (AM)a levels and/or excessive levels of Reactive Oxygen Species (ROS)b have previously been linked to delayed wound healing and presence of chronic wounds. We aimed to evaluate the effect of pre-operative supplementation with encapsulated fruit and vegetable juice powder concentrate (JuicePlus+®) on postoperative morbidity and Quality of Life (QoL)c. METHODS: We conducted a randomised, double-blind, placebo-controlled two-arm parallel clinical trial evaluating postoperative morbidity following lower third molar surgery. Patients aged between 18 and 65 years were randomised to take verum or placebo for 10 weeks prior to surgery and during the first postoperative week. The primary endpoint was the between-group difference in QoL over the first postoperative week, with secondary endpoints being related to other measures of postoperative morbidity (pain and trismus). RESULTS: One-hundred and eighty-three out of 238 randomised patients received surgery (Intention-To-Treat population). Postoperative QoL tended to be higher in the active compared to the placebo group. Furthermore, reduction in mouth opening 2 days after surgery was 3.1 mm smaller (95% CI 0.1, 6.1), the mean pain score over the postoperative week was 8.5 mm lower (95% CI 1.8, 15.2) and patients were less likely to experience moderate to severe pain on postoperative day 2 (RR 0.58, 95% CI 0.35, 0.95), comparing verum to placebo groups. CONCLUSION: Pre-operative supplementation with a fruit and vegetable supplement rich in AM may improve postoperative QoL and reduce surgical morbidity and post-operative complications after surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01145820; Registered June 16, 2010.

A case report of open craniofacial sutures, a novel feature of systemic sclerosis?

Scleroderma is an uncommon connective-tissue disease, its key feature being excessive collagen deposition resulting in fibrosis of the skin and internal organs. There are different types that can vary in severity from localized scleroderma to systemic sclerosis. Various clinical and radiographic findings can be attributed to the disease, which arise owing to the progressive nature of microvascular changes and collagen deposition. These include limited mouth opening, xerostomia, periodontal disease and cardiac and pulmonary disease. Whilst bone resorption has been reported, as far as we are aware, the literature has not described a case with failure of bony suture closure. Hence, we would like to describe what is probably a unique case of a patient with a 5-year history of systemic sclerosis, who was referred for management of increased mobility of her upper central incisors. Radiographic imaging (conventional and three-dimensional) confirmed increased bone resorption, partly owing to periodontal disease, but also owing to an open premaxillary suture. Similarly, other craniofacial sutures were diagnosed as being open, and, to our knowledge, this represents a yet undescribed finding in a patient suffering from scleroderma.

Development and application of LED arrays for use in phototherapy research.

Lasers/LEDs demonstrate therapeutic effects for a range of biomedical applications. However, a consensus on effective light irradiation parameters and efficient and reliable measurement techniques remain limited. The objective here is to develop, characterise and demonstrate the application of LED arrays in order to progress and improve the effectiveness and accuracy of in vitro photobiomodulation studies. 96-well plate format LED arrays (400-850 nm) were developed and characterised to accurately assess irradiance delivery to cell cultures. Human dental pulp cells (DPCs) were irradiated (3.5-142 mW/cm2 : 15-120 s) and the biological responses were assessed using MTT assays. Array calibration was confirmed using a range of optical and analytical techniques. Multivariate analysis of variance revealed biological responses were dependent on wavelength, exposure time and the post-exposure assay time (P < 0.05). Increased MTT asbsorbance was measured 24 h post-irradiation for 30 s exposures of 3.5 mW/cm2 at 470, 527, 631, 655, 680, 777, 798 and 826 nm with distinct peaks at 631 nm and 798 nm (P < 0.05). Similar wavelengths were also effective at higher irradiances (48-142 mW/cm2 ). LED arrays and high throughput assays provide a robust and reliable platform to rapidly identify irradiation parameters which is both time- and cost-effective. These arrrays are applicable in photobiomodulation, photodynamic therapy and other photobiomedical research.

The relevance of EGFR overexpression for the prediction of the malignant transformation of oral leukoplakia.

The present study evaluated the relevance of EGFR overexpression in prediction of malignant transformation of oral leukoplakia (OLP). The retrospective study comprised paraffin-embedded tissue samples of OLP that transformed into oral squamous cell carcinoma (OSCC) (n=53) and tissue samples of OLP that did not transform into OSCC (n=45) during a follow-up period of 5 years. EGFR overexpression was assessed immunohistochemically. A significantly different expression rate of EGFR was determined between transformed and non-transformed OLP (p=0.017). A statistically significant increase of EGFR expression for low dysplasia lesions in group I compared to group II was proven (D0, p=0.013; D1, p=0.049). By calculation of ROC curve and determination of highest Youden index the optimal threshold value [cut-off point (COP) = 44.96] for distinguishing the transformed from non-transformed lesions was estimated (critical expression rate of EGFR). Using the determined COP the correlation between high-risk lesions and the detection of increased expression rates were significant (p=0.001). In the future, the assessment of EGFR overexpression in OLP may allow identifying OLP lesions with an increased risk of malignant transformation that may have been regarded harmless when only the grade of dysplasia had been taken into account.

Detection of MAGE-A expression predicts malignant transformation of oral leukoplakia.

The study aimed at checking if MAGE-A expression in oral leukoplakia (OLP) lesions is related to malignant transformation. The 48 samples of OLP that transformed to oral squamous cell carcinoma (OSCC) (group 1) and 50 samples of OLP that did not transform to OSCC (group 2) were included in the study. The expression of MAGE-A was restricted to group 1. The correlation between malignant transformation and MAGE-A occurrence in OLP was statistically significant (p < .0001). Detection of MAGE-A may allow identifying OLP with a high risk of malignant transformation giving a view to a new approach to prevention of oral cancer.