Biologics Research Articles

Clinical remission in severe asthma: lights and shadows on an ambitious goal.

The aim of this study was Describe the latest evidence related to the concept of clinical remission in patients with severe asthma, focusing on the lights and shadows of this concept. The idea of clinical remission in severe asthma patients brings about a significant shift in the way asthma is treated and managed. Although there has yet to be unanimous agreement among various scientific societies on the precise definition, this concept can be extremely useful in advancing the treatment of the disease. Asthma is a common respiratory condition that affects more than 300 million people globally. It has variable symptoms and severity levels, with about 10% of patients experiencing severe asthma. While there have been advancements in treatment, severe asthma poses significant challenges. Recent approaches have focused on achieving clinical remission, which goes beyond symptom control to address underlying inflammation and biological processes. Clinical remission criteria include the absence of symptoms, reduced medication usage, and normalized inflammatory markers. Various biologic therapies show promise, with some patients achieving remission. However, remission's definition varies globally, hindering standardization and a valid comparison. Standardizing remission criteria and refining predictive factors are crucial for effective asthma management. Overall, achieving clinical remission offers hope for improved long-term outcomes in severe asthma patients.

Single-cell proteomics and transcriptomics capture eosinophil development and identify the role of IL-5 in their lineage transit amplification.

The activities, ontogeny, and mechanisms of lineage expansion of eosinophils are less well resolved than those of other immune cells, despite the use of biological therapies targeting the eosinophilia-promoting cytokine interleukin (IL)-5 or its receptor, IL-5Rα. We combined single-cell proteomics and transcriptomics and generated transgenic IL-5Rα reporter mice to revisit eosinophilopoiesis. We reconciled human and murine eosinophilopoiesis and provided extensive cell-surface immunophenotyping and transcriptomes at different stages along the continuum of eosinophil maturation. We used these resources to show that IL-5 promoted eosinophil-lineage expansion via transit amplification, while its deletion or neutralization did not compromise eosinophil maturation. Informed from our resources, we also showed that interferon response factor-8, considered an essential promoter of myelopoiesis, was not intrinsically required for eosinophilopoiesis. This work hence provides resources, methods, and insights for understanding eosinophil ontogeny, the effects of current precision therapeutics, and the regulation of eosinophil development and numbers in health and disease.

Percepción del impacto del tratamiento biológico endovenoso sobre el ámbito laboral y personal en pacientes con enfermedad inflamatoria intestinal

IntroductionIn the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. MethodsAll IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. ResultsA total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. ConclusionsThe intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.

Effectiveness and Safety of Tildrakizumab in Psoriasis Patients Who Failed Anti-IL17 Treatment: A 28-Week Real-Life Study.

Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, -12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness.

Benefit Design And Biosimilar Coverage In Medicare Part D: Evidence And Implications From Recent Reforms.

There is substantial disparity between Medicare Part D and employer-sponsored health insurance plans in the coverage of biosimilars and their reference biologics. These disparities may be due to design elements of Part D plans that encourage the adoption of more expensive biologic drugs. We undertook several analyses to illustrate the dynamics of benefit design incentives over time, compare formulary coverage in Part D plans with that of employer-sponsored plans, and study how the Bipartisan Budget Act of 2018 affected Part D formulary coverage. Using these analyses of Part D reforms enacted through the Bipartisan Budget Act, we discuss the implications of elements of the Inflation Reduction Act of 2022 that will be implemented in 2025. Biosimilar coverage increased by 23percentage points five quarters after the Bipartisan Budget Act was implemented. We predict that the Inflation Reduction Act will also have a positive effect on biosimilar coverage. Given ample evidence of a relationship between drug coverage and utilization, our results suggest that Medicare patients and the federal government could realize substantial savings if Part D formularies resembled those of employer-sponsored plans.

Early response to Tezepelumab in type-2 severe asthma patients non-responders to other biological treatments: a real-life study.

ABSTRACT BACKGROUND. Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios. OBJECTIVE. We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs. METHODS. Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs. RESULTS. Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2-3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings. CONCLUSION. In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings.

The current status and challenges of surgical treatment for chronic Achilles tendon rupture

With the growing demand for physical activity, an increasing number of individuals with chronic Achilles tendon ruptures are opting for surgical intervention. Surgical approaches encompass end-to end anastomosis, tendon flap techniques, tendon transfer procedures, and free tendon grafting, among others. When selecting the appropriate surgical method and determining the surgical indications, it is imperative to consider factors like the length of the Achilles tendon defect, patient age, aesthetic preferences, functional requirements, and local tissue conditions. As medical devices evolve and surgical techniques advance, the criteria for surgical intervention are also evolving. Drawing from existing literature evidence, it becomes crucial to define reasonable parameters for addressing Achilles tendon defects with each surgical technique, aligning more closely with clinical needs. Additionally, auxiliary technologies such as biologic therapy and innovative biomaterials have demonstrated promising results in laboratory or animal models. The focal point of advancing these auxiliary technologies lies in facilitating the translation of pertinent clinical outcomes in the future.

Assessment of the efficacy of comprehensive medical rehabilitation of patients with polypoid rhinosinusitis based on the international classification of functioning, disability and health

Abstract. Purpose of the study. The article discusses an algorithm for using the categories of the International Classification of Functioning, Disability and Health (ICF) for comparative assessment of the effectiveness of various medical rehabilitation programs for patients with polypoid rhinosinusitis. It is shown that the use of the ICF makes it possible to implement a systematic approach to assessing the efficacy of rehabilitation measures, taking into account the biopsychosocial model for assessing health (illness) and the category of functioning, which serves as the basis for the integration process of rehabilitation. The results of comparative monitoring of the formed categorical profile of a patient with polypoid rhinosinusitis convincingly proved the advantages of complex medical rehabilitation of patients with nasal polyposis, based on biological therapy with dupilumab in combination with a course application of an alternating magnetic field and low-intensity laser radiation.

Does the introduction of an infliximab biosimilar always result in savings for hospitals? A descriptive study using real-world data

BackgroundBiosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13.MethodsGastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping.ResultsSixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal.ConclusionsThe introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.

Total knee and hip replacement in rheumatoid arthritis: A current trend

Total joint replacement (TJR) is a surgical procedure widely used in severe destructive joint damage. TJR of the knee and hip joint (TKR and THR respectively) occupies an important place in the complex treatment of rheumatoid arthritis (RA) and osteoarthritis (OA), and can significantly reduce pain and improve function in patients with severe structural joint damage due to an ineffectiveness of conservative therapy. In recent years, due to the development of the modern concept of active treatment of RA (treat-to-target) and the introduction of new classes of anti-inflammatory drugs, such as biologic disease modifying antirheumatic drugs and JAK inhibitors, the need for TJR in RA has begun to decrease. At the same time, the aging of the population, the increase in the number of patients with OA and the lack of generally approved pathogenetic therapy determine the increase of TKR/THR incidence in this disease. This review presents the long-term dynamics of the incidence of TKR and THR according to the national registers of different countries. The issues of the complication risks in patients with RA and OA, current recommendations for anti-rheumatic therapy in RA in the perioperative period are also considered.

Short-term efficacy of vedolizumab in patients with inflammatory bowel disease in real-life settings in Bosnia and Herzegovina.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), necessitates effective management strategies. This study aims to evaluate the real-world efficacy of vedolizumab, a newer biological therapy, in treating IBD in Bosnia and Herzegovina. A retrospective observational study was conducted across 6 medical centers, involving 139 IBD patients, 76 with UC and 63 with CD. Patients were assessed for clinical remission and other outcomes at the 26-week mark post vedolizumab treatment initiation. At 26 weeks, clinical remission was achieved in 82.9% of UC patients and 85.7% of CD patients. Mucosal healing was observed in 38.1% of CD patients. The efficacy of vedolizumab did not significantly differ based on prior anti-tumor necrosis factor (TNF) exposure. Notably, the clinical scoring tools for predicting vedolizumab response showed limited applicability in this cohort. Vedolizumab demonstrated high efficacy in treating both UC and CD in a real-world settings in Bosnia and Herzegovina, underscoring its potential as a significant therapeutic option in IBD management.

Rheumatoid arthritis epidemiology: a nationwide study in Poland

To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013–2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients’ gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.

Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Evaluation of Clinical Remission in Best-Performing Severe Asthmatic Patients Treated for Three Years with Mepolizumab.

In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. According to the criteria, 39-52% of patients experienced complete remission in the first year, increasing to 51-73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.

Krüppel-like Factor-4-Mediated Macrophage Polarization and Phenotypic Transitions Drive Intestinal Fibrosis in THP-1 Monocyte Models In Vitro.

Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD.

CORNEAL TRANSPLANTATION

Corneal transplantation is an ophthalmic surgery that aims to restore vision in patients with corneal diseases. Advances in transplantation techniques and in the treatment of rejection have improved the results of this procedure, making it more effective and safer. This paper seeks to analyze the latest developments in transplantation techniques and treatments for rejection in corneal transplantation, highlighting not only scientific advances, but also the emotional and social aspects involved in this procedure, providing a comprehensive overview of the latest innovations in the field of corneal transplantation, highlighting improvements in surgical techniques and post-operative treatments, which are helping to transform the lives of thousands of patients around the world. This is a bibliographical review, using qualitative premises, with the PubMed, Scopus, Web of Science and Scielo databases. The health descriptors “corneal transplantation”, “corneal graft rejection” and “penetrating keratoplasty” were used to better refine the research. Corneal transplantation is indicated for various conditions, such as keratoconus, corneal dystrophies, corneal opacities, among others. The most common transplant techniques include complete (penetrating) corneal transplantation, anterior lamellar transplantation and endothelial transplantation (DSAEK/ DMEK). In recent years, there have been significant advances in lamellar transplantation techniques, which allow specific layers of the cornea to be replaced while preserving the healthy layers. This has resulted in better success rates and faster visual recovery compared to penetrating transplantation. Treatment of corneal graft rejection includes the use of topical and systemic corticosteroids, immunosuppressants and anti-inflammatory agents. New approaches, such as biological and immunomodulatory therapies, are also being investigated to improve results in cases of refractory graft rejection. In conclusion, corneal transplantation remains an important option for restoring vision in patients with corneal diseases. Updates in transplantation techniques and advances in the treatment of rejection have improved the results of this procedure, providing patients with a better quality of life and faster and more effective visual recovery.

Advances in precision therapy of low-grade serous ovarian cancer: A review.

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer that accounts for approximately 6% to 10% of serous ovarian cancers. The clinical treatment of LGSOC is similar to that of high-grade serous ovarian carcinoma, however, its clinical and molecular characteristics are different from those of high-grade serous ovarian carcinoma. This article reviews the research on gene diagnosis, surgical treatment, chemotherapy, and biological therapy of LGSOC, providing reference for clinical diagnosis and treatment of LGSOC. Surgery is the cornerstone of LGSOC treatment and maximum effort must be made to achieve R0 removal. Although LGSOC is not sensitive to chemotherapy, postoperative platinum-based combination chemotherapy remains the first-line treatment option for LGSOC. Additional clinical trials are needed to confirm the clinical benefits of chemotherapy and explore new chemotherapy protocols. Hormone and targeted therapies may also play important roles. Some patients, particularly those with residual lesions after treatment, may benefit from hormone maintenance therapy after chemotherapy. Targeted therapies, such as MEKi, show good application prospects and are expected to change the treatment pattern of LGSOC. Continuing to further study the genomics of LGSOC, identify its specific gene changes, and combine traditional treatment methods with precision targeted therapy based on second-generation sequencing may be the direction for LGSOC to overcome the treatment bottleneck. In future clinical work, comprehensive genetic testing should be carried out for LGSOC patients to accumulate data for future scientific research, in order to find more effective methods and drugs for the treatment of LGSOC.

Diagnosis, management and therapeutic options for eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic and commonly evolving condition leading to relevant and potentially irreversible burden in terms of tissue damage and related functional impairment, thus significantly impacting on quality of life. The aim of the present review is to summarize the recent advances in terms of diagnostic work-up and pharmacological and nonpharmacological management of the disease, under the broader perspective of type 2 inflammation. Two major novelties have prompted an innovative approach to EoE. In terms of diagnosis, it has been proposed to dissect the disease heterogeneity in three endotypes, independent from tissue eosinophil number: EoEe1, characterized by normal appearing oesophagus; EoEe2, associated with type 2 inflammation and steroid-refractoriness; EoEe3, whose features include adult onset, a more fibro-stenotic aspect and loss of epithelial gene expression. Concerning treatment, two recently licensed drugs for EoE, oro-dispersible budesonide and dupilumab represent the first treatment options specifically developed for EoE and addressing EoE-related peculiar pathobiological features. In the era of precision medicine, managing EoE according to a phenotype-driven approach might be helpful in defining the best treatment options in the different disease forms or stages. In addition, exploring the coexistence or the previous occurrence of other type 2 conditions may suggest the opportunity to specifically target type 2 inflammation through biologic therapy. The complex EoE pathobiology combining inflammatory and functional features, both at organ and systemic level, requires a multidimensional approach relying on the strict integration of gastroenterologists and allergist-immunologists.

Artificial Intelligence for Quantifying Cumulative Small Bowel Disease Severity on CT-Enterography in Crohn's Disease.

Assessing the cumulative degree of bowel injury in ileal Crohn's disease (CD) is difficult. We aimed to develop machine learning (ML) methodologies for automated estimation of cumulative ileal injury on CT-enterography (CTE) to help predict future bowel surgery. Adults with ileal CD using biologic therapy at a tertiary care center underwent ML analysis of CTE scans. Two fellowship trained radiologists graded bowel injury severity at granular spatial increments along the ileum (1cm), called mini-segments. ML segmentation methods were trained on radiologist grading with predicted severity then spatially mapped to the ileum. Cumulative injury was calculated as the sum (S-CIDSS) and mean of severity grades along the ileum. Multivariate models of future small bowel resection were compared cumulative ileum injury metrics and traditional bowel measures, adjusting for laboratory values, medications, and prior surgery at the time of CTE. In 229 CTEs, 8424 mini-segments underwent analysis. Agreement between ML and radiologists injury grading was strong (κ=0.80, 95%CI 0.79-0.81) and similar to inter-radiologist agreement (κ=0.87, 95%CI 0.85-0.88). S-CIDSS (46.6 vs. 30.4, P=0.0007) and mean cumulative injury grade scores (1.80 vs. 1.42, P<0.0001) were greater in CD biologic users that went to future surgery. Models using cumulative spatial metrics (AUC=0.76) outperformed models using conventional bowel measures, laboratory values, and medical history (AUC=0.62) for predicting future surgery in biologic users. Automated cumulative ileal injury scores show promise for improving prediction of outcomes in small bowel CD. Beyond replicating expert judgement, spatial enterography analysis can augment the personalization of bowel assessment in CD.

Impact of Biologic Therapy on Key Cardiovascular Risk Parameters in a Psoriatic Cohort-a Retrospective Review.

Psoriasis is a risk factor for cardiovascular disease. Biologic agents have revolutionised psoriatic skin control. This study aims to assess the change in cardiovascular risk factors in a cohort of patients treated with 1 year of continuous biologic treatment. A retrospective medical record review was conducted of consecutive patients receiving biologic therapy for chronic plaque psoriasis in a single dermatology centre at a major tertiary hospital in Australia. The effect of biologic therapy on psoriasis was assessed using a psoriasis area severity index (PASI). Cardiovascular risk factors included systolic blood pressure (SBP), diastolic BP (DBP), heart rate (HR) and body mass index (BMI). Measurements at baseline and 1-year follow-up were compared using paired t-tests. A total of 106 patients were reviewed with a median age of 44 years, and 63% of the patients were male. At baseline, mean BMI was 30 (SD 7), mean SBP was 129 (SD 17), mean DBP was 81 (SD 9) and mean HR was 82 (SD 14). Over 12months, the PASI was reduced from 17.4 (SD 8.5) to 1.4 (SD 1.7, p < 0.001) indicating skin improvement. There was no significant difference from baseline in SBP (difference 2.3mmHg, 95% CI - 1.4-5.9), DBP (0.6mmHg, 95% CI - 1.2-2.5), BMI (difference - 0.1kg/m2, 95% CI - 0.9-0.7) or HR (difference 1.3, 95% CI - 3.9-6.4). In patients with psoriasis, markers of cardiovascular disease risk did not improve after 1year of biologic therapy despite significant improvements in psoriasis skin severity.