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Background: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. Objective: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. Methods: We studied 180 SNPs in patients with moderate‐to‐severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. Results: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR‐146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83–0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. Conclusion: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non‐response to this drug in patients with plaque psoriasis. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing interest in the utilization of biologic therapies for the management of asthma. Both TSLP and IgE are important immune molecules in the development of asthma, and they are involved in the occurrence and regulation of inflammatory response. Methods: A comprehensive search of PubMed and Web of Science was conducted to gather information on anti-TSLP antibody and anti-IgE antibody. Results: This investigation elucidates the distinct mechanistic roles of Thymic Stromal Lymphopoietin (TSLP) and Immunoglobulin E (IgE) in the pathogenesis of asthma, with a particular emphasis on delineating the therapeutic mechanisms and pharmacological properties of monoclonal antibodies targeting IgE and TSLP. Through a meticulous examination of clinical trials involving paradigmatic agents such as omalizumab and tezepelumab, we offer valuable insights into the potential treatment modalities for diseases with shared immunopathogenic pathways involving IgE and TSLP. Conclusion: The overarching objective of this comprehensive study is to delve into the latest advancements in asthma therapeutics and to provide guidance for future investigations in this domain. [ABSTRACT FROM AUTHOR]

Background: Demodex density is known to increase in various immunosuppressive conditions. The relationship between biologic therapy and Demodex density remains unknown. We aimed to investigate whether the density of Demodex mites is higher in psoriasis patients treated with biologic agents compared to treatment‐naive or topically treated patients. Methods: A cross‐sectional study was conducted, comparing psoriasis patients receiving biologic therapy (n = 34) with controls (n = 33). Demodex density was assessed using the standardized skin surface biopsy technique (SSSB). Statistical analysis was performed to compare the densities and prevalence of demodicosis between the two groups. Results: Demodex density was significantly higher in the biologic therapy group compared to the control group on the right cheek (7.29 vs. 0.12/cm2; P = 0.001), left cheek (8.15 vs. 0.24/cm2; P = 0.002), and whole face (average of all four regions: 5.50 vs. 0.80/cm2; P = 0.001). The prevalence of demodicosis was significantly higher in the biologic therapy group on the forehead (35.3% vs. 12.1%; P = 0.043), right cheek (41.2% vs. 0%; P < 0.001), and left cheek (44.1% vs. 0%; P < 0.001). The frequency of cases with demodicosis in at least one localization was higher in the biological therapy group compared to the control group (61.8% vs. 15.2%; P < 0.001). Conclusions: Psoriasis patients receiving biologic therapy had a higher Demodex density and prevalence of demodicosis compared to controls. Biologics may lead to an increase in Demodex density by blocking specific cytokines, such as interleukin‐17 and tumor necrosis factor‐α, which play a role in immunity against Demodex. Further research is needed to explore the impact of different biological agents on Demodex density. Plain Language Summary: "Demodex" mites live in human hair follicles, usually without causing any harm. However, when the immune system is suppressed due to several conditions, the Demodex density (Dd) can increase. "Biological drugs" that suppress some immunity elements are used to treat psoriasis. We aimed to determine if Dd increases in 34 psoriasis patients using biological therapies compared to those who do not. Dd on the face was significantly higher in the biological treatment group compared to the controls. The blockage of certain immune system molecules by biological drugs could explain this. [ABSTRACT FROM AUTHOR]

Background: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. Methods: We performed a single‐centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. Results: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re‐epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. Conclusions: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first‐line approach for severe forms, but using biological immunosuppressants is promising. [ABSTRACT FROM AUTHOR]

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non‐smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non‐smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144. [ABSTRACT FROM AUTHOR]

Background: Prior work showed that patients from the CorEvitas Psoriasis Registry who had previously failed a prior biologic and then initiated ixekizumab demonstrated improvements in disease severity and patient-reported outcomes after 6 months. However, newer therapies such as interleukin-23 inhibitors (IL-23i) were not considered. Here, with more recent data including IL-23i, 6-month effectiveness of ixekizumab following a switch from any biologic was assessed as well as whether 6-month effectiveness of ixekizumab was impacted by prior biologic class. Methods: We included CorEvitas Psoriasis Registry patients who initiated ixekizumab after discontinuing another biologic therapy and had a corresponding 6-month follow-up visit following ixekizumab initiation (N = 743, 2016–2023). Immediate prior biologic class was categorized as tumor necrosis factor inhibitor (TNFi) or interleukin-12/23 inhibitors (IL-12/23i, n = 405), non-ixekizumab interleukin-17i (IL-17i, n = 237), or IL-23i (n = 101). Adjusted mean changes in body surface area (BSA), Dermatology Life Quality Index (DLQI), itch, and skin pain were calculated for prior biologic class groups using analysis of covariance (ANCOVA). Proportions achieving ≥ 75%, ≥ 90%, and ≥ 100% improvement in Psoriasis Area and Severity Index (PASI75, PASI90, and PASI100, respectively), Investigator's Global Assessment (IGA) 0/1, and DLQI 0/1 were calculated for all patients and compared among prior biologic classes via relative risks (RRs) and 95% confidence intervals (CIs) using multivariable modified Poisson regression. Results: Mean improvements in BSA, DLQI, itch, and skin pain, were 7.6, 3.6, 23.3, and 16.7, respectively, for ixekizumab patients who switched from TNFi or IL-12/23i (all p < 0.05); 6.8, 3.3, 19.6, and 14.1, respectively, for those who switched from non-ixekizumab IL-17i (all p < 0.05); and 7.8, 3.4, 22.2, and 12.8, respectively, for those who switched from IL-23i (all p < 0.05). Overall, 54%, 41%, and 31% of ixekizumab initiators achieved PASI75, PASI90, and PASI100, respectively, 50% maintained or achieved IGA 0/1, and 48% maintained or achieved DLQI 0/1. The prior TNFi or IL-12/23i group was 31% more likely to achieve PASI100 (RR = 1.31, 95% CI 1.01, 1.69) and 32% more likely to maintain or achieve IGA 0/1 (RR = 1.32, 95% CI 1.11, 1.57), but not significantly more likely to achieve PASI90. The prior IL-23i group was 45% more likely to achieve PASI90 (RR = 1.45, 95% CI 1.10, 1.91), 55% more likely to achieve PASI100 (RR = 1.55, 95% CI 1.12, 2.13), and 39% more likely to maintain or achieve IGA 0/1 (RR = 1.39, 95% CI 1.12, 1.73) compared to the prior non-ixekizumab IL-17i group. Achievement of PASI75 and DLQI 0/1 was consistent across the prior TNFi or IL-12/23i, IL-23i, and non-ixekizumab IL-17i groups. Conclusions: These updated findings with IL-23i data reaffirm that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity and patient-reported outcomes at 6 months in real-world settings. Compared to patients who switched from another IL-17i, patients who switched class from a TNFi or IL-12/23i were more likely to achieve PASI100 and IGA 0/1, and patients who switched class from an IL-23i were more likely to achieve PASI90 in addition to PASI100 and IGA 0/1. [ABSTRACT FROM AUTHOR]

Objective. To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. Methods. Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. Results. A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. Conclusion. No significant differences were found between treatments in long-term survival due to inefficacy or AEs. [ABSTRACT FROM AUTHOR]

This review provides an overview of evidence supporting the existence of distinct homeostatic and inflammatory eosinophil subpopulations in health and disease. Particular emphasis is placed on describing the phenotypic and functional roles of these eosinophil subtypes in asthma, as well as the phenotypic changes induced by clinical therapy with the anti-IL-5 biologic agent, mepolizumab. Improved understanding of distinct eosinophil phenotypes may enable targeting of select subpopulations in the treatment of patients with type 2 inflammatory diseases such as asthma. [ABSTRACT FROM AUTHOR]

Aim: This study sought to assess hepatitis B virus (HBV) serology and the incidence of HBV reactivation (HBVr) in rheumatology patients with resolved hepatitis B infection (HBsAg negative and HBcAb positive) who were undergoing treatment with biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Material and Method: Data from rheumatology patients treated with b/tsDMARDs were retrospectively reviewed from the electronic records. The demographic data, the anti-rheumatic drugs used, and the hepatitis serologies (HBsAg, anti-HBc IgG, anti-HBs, and anti-HCV) of the patients were analyzed. Results: The study included a total of 316 patients, of whom 217 (68.7%) were diagnosed with ankylosing spondylitis, 74 (23.4%) with rheumatoid arthritis, and 25 (7.9%) with psoriatic arthritis. Evaluation of the patients' viral serologies revealed that four (1.2%) were HBsAg positive, and 18 (5.7%) were HBsAg negative and HBcAb positive. Anti-HCV positivity was observed in one. Conclusion: The rate of resolved hepatitis B infection is relatively high in patients under rheumatologic follow-up. However, the use of biologics in these patients poses a low risk of HBVr. [ABSTRACT FROM AUTHOR]

Anti-mitochondrial antibody (AMA)-positive myopathy, a recently identified condition with significant cardiac involvement, poses a serious challenge in treatment consensus due to its extreme rarity. While several studies demonstrate the efficacy of high-dose prednisolone in managing this disease, the current literature lacks substantial evidence regarding the effectiveness of biologic therapy or low-dose prednisolone for remission induction. Here, we present a case of AMA-positive myocarditis that emerged during rheumatoid arthritis treatment with tocilizumab (TCZ) and low-dose prednisolone (PSL). Successfully, intensive immunosuppressive therapy with high-dose PSL proved effective in stabilizing this condition. Our case highlights the necessity of a robust immunosuppressive approach, favoring high-dose PSL over the combination of low-dose PSL and TCZ in this disease. [ABSTRACT FROM AUTHOR]

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children. [ABSTRACT FROM AUTHOR]

Juvenile idiopathic inflammatory myopathy (JIIM) is a rare systemic autoimmune disease characterized by skeletal muscle weakness with or without a skin rash. Juvenile dermatomyositis (JDM) is the most common subtype of JIIM, accounting for 80% of JIIM. Recent studies identified several myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). Each MSA or MAA is associated with distinct clinical features and outcomes, although there are several differences in the prevalence of MSA/MAA and autoantibody–phenotype relationships between age and ethnic groups. Histopathological studies have revealed critical roles of type I interferons and vasculopathy in the development of JDM. Serological classification mostly corresponds to clinicopathological classification. Novel therapeutic agents, such as biologics and Janus kinase inhibitors (JAKi), have been developed; however, to date, there is a lack of high-level evidence. As advances in treatment have reduced the mortality rate of JIIM, recent studies have focused on medium- and long-term outcomes. However, rapidly progressive interstitial lung disease (RP-ILD) remains a major cause of death in anti-melanoma differentiation gene 5 autoantibody-positive JDM. Early diagnosis and intervention using a multi-drug regimen is critical for the treatment of RP-ILD. Rituximab and JAKi may reduce mortality in patients with JDM-associated RP-ILD refractory to conventional therapy. [ABSTRACT FROM AUTHOR]

Introduction: The management of Crohn's disease (CD) in the Middle East, like in other parts of the world, is rapidly evolving with the introduction of novel advanced medical and biological therapies. In the United Arab Emirates (UAE), several biological therapies are used to achieve remission in severe and resistant cases of CD. We carried out a literature search to analyze the effectiveness and safety of biologic treatments currently licensed in the UAE. Methods: We searched the PubMed, Embase and Cochrane library databases from inception to January 2020 to identify relevant studies. Search terms were generated using established treatment guidelines for CD. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: Biologic and small molecule agents for CD include four core drug classes: anti-tumor necrosis factor-α agents (TNF-α), integrin receptor antagonists, Janus kinase (JAK) inhibitors and IL-12/IL-23 antagonists. All drug classes showed good efficacy and safety in managing patients with CD. Some drug classes had distinguishable side effect profiles. This included an increased lymphoma and tuberculous risk for TNF-α and integrin receptor antagonists. Many trials supported the effectiveness of these licensed drugs. Biologic agent intolerance was common; one-third of patients receiving TNF-α treatment will develop intolerance to that specific drug. Conclusions: Advanced medical therapies licensed in the UAE have proven to be safe and efficacious. Additional research is required to evaluate the safety and efficacy of newer biologics and biosimilars. [ABSTRACT FROM AUTHOR]

The abiotic/abiotic hybrid S@UIL system enhances ICD-associated antitumor effects by inducing excessive autophagy and mild-temperature photothermal therapy. [Display omitted] The tumor microenvironment, characterized by hypoxia, supports the efficacy of anaerobic bacteria like attenuated S. typhimurium in cancer therapies. These bacteria target and penetrate deep tumor regions, significantly reducing tumor size but often lead to tumor regrowth due to limited long-term efficacy. To enhance the therapeutic impact, a novel biohybrid system, S@UIL, has been developed by coating S. typhimurium with a zirconium-based nanoscale metal–organic framework (UiO-66-NH 2) loaded with indocyanine green (ICG) and luteolin (LUT). This system maintains the bacteria's tumor-targeting ability while increasing the penetration and therapeutic effectiveness through excessive autophagy and mild hyperthermia. In a subcutaneous colon cancer model, the integration of LUT and ICG promotes autophagic cell death and photothermal sensitization, leading to the release of damage-associated molecular patterns (DAMPs). These DAMPs activate immune responses through dendritic cells and T -cells, enhancing immunogenic cell death (ICD) and potentially reducing immune evasion by tumors. This single-administration approach also integrates multimodal imaging capabilities, providing a promising strategy for improved tumor ICD induction and cancer progression inhibition. [ABSTRACT FROM AUTHOR]

Introduction: Severe asthma is a chronic respiratory condition that affects a significant number of individuals, causing persistent inflammation of the airways and leading to recurrent symptoms such as wheezing, coughing, and shortness of breath. While conventional asthma treatments, including inhaled corticosteroids and bronchodilators, are generally effective for most asthma patients, they may not always provide sufficient relief for individuals with severe asthma. In such cases, the use of biologic agents licensed specifically for severe asthma can be a valuable treatment option. Aim of the study: This article aims to explore the different biologic agents licensed for severe asthma and delve into their effectiveness in managing this complex and challenging condition. Material and methods: Literature available in the PubMed database was reviewed using the following keywords: biologic agents for asthma; omalizumab; mepolizumab; bernalizumab; tezepelumab; monoclonal antibodies. Conclusions: These medications are designed to target the underlying mechanisms of severe asthma, addressing the root causes of the condition rather than just managing the symptoms. As a result, they have shown promising results in improving symptoms and reducing exacerbations in individuals with severe asthma. By understanding the potential benefits of these medications, healthcare professionals can make informed decisions when it comes to treating patients with severe asthma. [ABSTRACT FROM AUTHOR]

Immune check inhibitors (ICIs) are a class of biologic therapy used for cancer treatment that enhances T-cell recognition of cancer cells. Toxicities from ICIs are described as immune-related adverse events (irAEs) with Grade 1 to 2 irAEs representing mild-to-moderate toxicity and Grade 3 to 4 irAEs representing severe to life-threatening toxicity. The long half-life of ICIs contributes to the extended and unpredictable nature of irAEs. ICI therapy is typically stopped for Grade 3 to 4 irAEs except for endocrinopathies if clinically optimized. Toxicities can involve any organ system; therefore, a thorough preoperative assessment is imperative to ensure appropriate clinical management. [ABSTRACT FROM AUTHOR]

Introduction: Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time. Methods: This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8. Results: Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250 µg/g) and biomarker normalization (FC ≤ 100 µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS]≤1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], p < 0.001). Conclusion: In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response. [ABSTRACT FROM AUTHOR]

Abstract C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r 1) value (21.87 mM−1S−1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.

Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into NAD + within the body after ingestion. NMN plays a pivotal role in several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. NMN has emerged as a key focus of research in the fields of biomedicine, health care, and food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights into the pathogenesis of age- and aging-related diseases. Given the sustained global research interest in NMN and the substantial market expectations for the future, here, we comprehensively review the milestones in research on NMN biotherapy over the past 10 years. Additionally, we highlight the current research on NMN in the field of digestive system diseases, identifying existing problems and challenges in the field of NMN research. The overarching aim of this review is to provide references and insights for the further exploration of NMN within the spectrum of digestive system diseases. [ABSTRACT FROM AUTHOR]

Hypertrophic scarring is an aberrant wound-healing response to reestablish dermal integrity after an injury and can cause significant abnormalities in physical, aesthetic, functional, and psychological symptoms, impacting the patient's quality of life. There is currently no gold standard for preventing and treating hypertrophic scars. Therefore, many researchers have attempted to search for antihypertrophic scar agents with greater efficacy and fewer side effects. Natural therapeutics are becoming attractive as potential alternative anti-scarring agents because of their high efficacy, safety, biocompatibility, low cost, and easy accessibility. This review demonstrates various kinds of natural product-based therapeutics, including onion, vitamin E, Gotu kola, green tea, resveratrol, emodin, curcumin, and others, in terms of their mechanisms of action, evidence of efficacy and safety, advantages, and disadvantages when used as anti-scarring agents. We reviewed the literature based on data from in vitro, in vivo, and clinical trials. A total of 23 clinical trials were identified in this review; most clinical trials were ranked as having uncertain results (level of evidence 2b; n = 16). Although these natural products showed beneficial effects in both in vitro and in vivo studies of potential anti-scarring agents, there was limited clinical evidence to support their efficacy due to the limited quality of the studies, with individual flaws including small sample sizes, poor randomization, and blinding, and short follow-up durations. More robust and well-designed clinical trials with large-scale and prolonged follow-up durations are required to clarify the benefits and risks of these agents. [ABSTRACT FROM AUTHOR]

Background: Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains. Method: In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI. Result: Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI. Conclusion: Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI. [ABSTRACT FROM AUTHOR]

Introduction: Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC); however, their precise contributions remain unclear. The present study aimed to investigate the diagnostic value of the activated NK-associated gene (ANAG) score in UC and evaluate its predictive value in response to biological therapy. Methods: Bulk RNA-seq and scRNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) and Single Cell Portal (SCP) databases. In the bulk RNA-seq, differentially expressed genes (DEGs) were screened by the “Batch correction” and “Robust rank aggregation” (RRA) methods. The immune infiltration landscape was estimated using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. DEGs that correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen key ANAGs and establish an ANAG score. The expression levels of the four key ANAGs were validated in human samples by real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence. The potential therapeutic drugs for UC were identified using the DSigDB database. Through scRNA-seq data analysis, the cell scores based on the ANAGs were calculated by “AddModuleScore” and “AUCell.” Results: Immune infiltration analysis revealed a higher abundance of activated NK cells in noninflamed UC tissues (ssGSEA, p < 0.001; CIBERSORT, p < 0.01). Fifty-four DEGs correlated with activated NK cells were identified as ANAGs. The ANAG score was established using four key ANAGs (SELP, TIMP1, MMP7, and ABCG2). The ANAG scores were significantly higher in inflamed tissues (p < 0.001) and in biological therapy nonresponders (NR) tissues before treatment (golimumab, p < 0.05; ustekinumab, p < 0.001). The ANAG score demonstrated an excellent diagnostic value (AUC = 0.979). Patients with higher ANAG scores before treatment were more likely to experience a lack of response to golimumab or ustekinumab (golimumab, p < 0.05; ustekinumab, p < 0.001). Conclusion: This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is a chronic inflammatory condition of the gut. It has two major subtypes Crohn's disease and ulcerative colitis. The follow-up consists of radiologic, molecular, endoscopic, and histological assessments. Intestinal ultrasound (IUS) is a noninvasive measure that provides future hope in guiding the management of IBD patients. This study is to assess the effectiveness of IUS in IBD patients' follow-up in our tertiary center during the pandemic. This is a prospective observational study during the COVID-19 pandemic. We used IUS to assess activity of IBD at baseline and at 6-month follow-up of patients on maintenance biological therapy using the following parameters: bowel haustrations, stratification, bowel wall thickness (BWT), Doppler sign (Limberg classification), presence of lymph nodes, or fibrofatty infiltration, echogenicity of the bowel, and presence of fistulae or abscesses. We compared the IUS with other radiologic parameters, histologic, and endoscopic scores at baseline before therapy, while we compared IUS with clinical scores and laboratory parameters before and after 24 weeks of biological treatment. Results: The cohort included 50 known IBD patients from June 2021 to January 2022. The laboratory studies showed a significant improvement in the hemoglobin indices, CRP, and fecal calprotectin from baseline and after 24 weeks. BWT, lumen diameter, lymph node presence, inflammatory signs, and Doppler activity signs were the most significant parameters in detecting improvement. However, there was no significant correlation between fecal calprotectin levels and ultrasound parameters. There was a positive correlation between MR and CT enterography, endoscopic parameters, and IUS parameters at baseline. Conclusions: IUS is an effective tool for follow-up of IBD patients especially during the pandemic periods. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cause of death and morbidity among women. A major challenge for clinical management of breast cancer is the dissemination of breast cancer cells from the primary tumor site via lymphatic drainage, resulting in metastatic tumor spread. Recent studies have found that high expression of the microRNA miR‐146a‐5p is associated with better survival outcomes for breast cancer patients. However, the mechanisms for this prognostic benefit are not fully elucidated, including whether or not miR‐146a‐5p plays a role in suppression of lymphatic dissemination. In this study, we investigated the role and uncovered functional mechanisms of miR‐146a‐5p in breast cancer. We found that high expression of miR‐146a‐5p is associated with better clinical outcomes, specifically in the patients with N0 breast cancer. In culture, miR‐146a‐5p overexpression in MCF‐7 breast cancer cells suppressed cell migration and lymphangiogenesis in lymphatic endothelial cells. When implanted in the mammary fat pad of mice, we observed that miR‐146a‐5p overexpressing MCF‐7 suppressed lymphatic dissemination but had no effect on tumor progression in the primary site. This suppression was associated with fewer disseminated cancer cells and reduced lymphangiogenesis in the draining and distal lymph nodes. In conclusion, these results suggest that miR‐146a‐5p can exhibit a protective role against breast cancer metastasis, and it can be a therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV1 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV1 (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV1%, FVC%, AEs rate, and OCS use. FEV1% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20 years, the improvement of knowledge on the pathogenesis of the disease has made available several drugs targeting key elements of the pathogenetic process, which now represent the preferred treatment option after the failure of first-line therapy with conventional drugs such as methotrexate (MTX). To this category of targeted drugs belong anti-cytokine or cell-targeted biological agents and more recently also Janus kinase inhibitors (JAKis). In the absence to date of specific biomarkers to guide the therapeutic choice in the context of true precision medicine, the choice of the first targeted drug after MTX failure is guided by treatment cost (especially after the marketing of biosimilar products) and by the clinical characteristics of the patient (age, sex, comorbidities and compliance) and the disease (presence or absence of autoantibodies and systemic or extra-articular manifestations), which may influence the efficacy and safety profile of the available products. This viewpoint focuses on the decision-making process underlying the personalized approach to RA therapy and will analyse the evidence in the literature supporting the choice of individual products and in particular the differential choice between biological drugs and JAKis. [ABSTRACT FROM AUTHOR]

Background: To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients. Results: The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients' demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%. Conclusion: While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index. Trial registration: NCT05105217. Registered 3 November 2021 [ABSTRACT FROM AUTHOR]

Nowadays, biological therapies are booming and more of these formulations are coming to the market. Platelet‐rich plasma, or PRP, is one of the most widely used biological therapies due to its ease of obtention and autologous character. Most of the techniques to obtain PRP are focusing on new processes and methods of optimization. However, not enough consideration is being given to modify the molecular components of PRP to generate more effective formulations with the aim of improving PRP treatments. Therefore, this review covers different novel PRP‐obtaining methods that attempt to modify the molecular composition of the plasma. [ABSTRACT FROM AUTHOR]

Background: Biologics has been known to be effective for patients with psoriasis. However, optimal treatment pathways and their cost-effectiveness are limited in a resource-limited country. This study assessed the cost-effectiveness of different sequential biologics for moderate-to-severe plaque psoriasis. Method: A hybrid model from a societal perspective was used. Model inputs were derived from network meta-analysis, clinical trials, and published literature. Three different sequential biologic treatments were assessed; Sequence 1; 1st Interleukin-17 (IL-17) inhibitor (secukinumab) followed by 2nd IL-17 inhibitors (ixekizumab or brodalumab), then 3rd IL-23 inhibitor (guselkumab), Sequence 2; ixekizumab followed by secukinumab or brodalumab, then guselkumab, and Sequence 3; brodalumab followed by ixekizumab or secukinumab, then guselkumab. Methotrexate or ciclosporin was used as standard of care (SoC). Results: All three different sequential biologic therapies could gain total quality-adjusted life year (QALY), but they had higher cost than SoC. Sequence 1 had the lowest incremental cost-effectiveness ratio (ICER) compared to SoC at 621,373 THB/QALY (19,449 $/QALY). ICER for Sequence 2 was 957,258 THB/QALY (29,962 $/QALY), while that for Sequence 3 was 1,332,262 THB/QALY (41,700 $/QALY). Fully incremental analysis indicated that Sequence 3 was dominated by Sequence 1 and Sequence 2. ICER for Sequence 2 was 7,206,104 THB/QALY (225,551 $/QALY) when compared to Sequence 1. Conclusion: At the current willingness-to-pay of 160,000 THB/QALY, no sequential IL-17 inhibitor was cost-effective compared to SoC. Secukinumab followed by ixekizumab or brodalumab then guselkumab (Sequence 1) may be the most appropriate option compared with other treatments. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterised by recurrent painful nodules, abscesses, fistulas and scarring. The primary distinguishing factor in the complex, yet still not fully understood, pathogenesis is an inflammation occurring within the hair follicle, followed by an immune response leading to further development of the skin lesions seen in HS. The treatment of patients with HS is very difficult due to the complexity of the lesions and the frequent tendency to recurrence, which also has a negative impact on the psychological state of patients and directly translates into a reduced quality of life. This review article addresses the pathogenesis, clinical presentation of HS and, in particular, explores the new therapeutic options available. [ABSTRACT FROM AUTHOR]

Paediatric non-infectious uveitis can lead to vision loss and permanent damage to the eye. It is difficult to diagnose, as it often presents asymptomatically, and can have a different aetiology compared with adult-onset non-infectious uveitis. Treatment depends on the cause of uveitis and the region of the eye affected, but generally involves corticosteroids, conventional immunosuppressive agents and biologic agents either as monotherapies or as combination therapies. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid is an autoantibody-mediated subepidermal blistering disorder which develops predominately in patients of advanced age. Corticosteroids remain as the first line of treatment for this disorder, although for difficult-to-treat cases (relapsing, corticosteroid-dependent, corticosteroid-resistant) or where corticosteroids are contraindicated, conventional immunotherapy or newer biologic agents can be used (as adjuvant or monotherapy). While new biologics are under evaluation for bullous pemphigoid, stronger evidence is still required for the majority of these new treatments. [ABSTRACT FROM AUTHOR]

Objective: Transforming growth factor-beta (TGF-β), an anti-inflammatory cytokine, plays a crucial role in restraining the proliferation and differentiation of T effector cells in autoimmune diseases. Glycoprotein A repetitions predominant (GARP), belonging to the leucine-rich repeat protein family, functions in facilitating the presentation of TGF-β on the surface of regulatory T-cells. The study aims to evaluate the activity of regulatory T-cell in Iraqi patients with psoriasis, treated with topical and biological therapy considering the level of TGF-β1 and LRRC32 gene (GARP) expression. Materials and Methods: In this study 22 blood samples of psoriasis patients and 24 healthy samples as a control group were analyzed to measure the level of TGF-β1 by enzyme-linked immunosorbent assay and the gene expression level of the LRRC32 (GARP gene) by quantitative reverse transcription polymerase chain reaction technique. Results: The results showed a significant decrease (p=0.004) in the level of TGF-β1 in the serum of patients with psoriasis treated with topical therapy and others treated with biological therapy compared to the control group. A significant increase (p=0.05) in the folding of LRRC32 gene expression was detected in psoriasis patients compared to the control percentage (100%). Moreover, there was a significant increase (p=0.000) in the percentage of the gene expression folding of LRRC32 gene in patients treated with biological therapy and patients treated with topical therapy compared to control percentage (100%). Conclusions: The high expression of the LRRC32 gene in patient samples is an indication of the effective role of regulatory T-cells under biological and topical treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Royal Darwin Hospital (RDH) is the sole public dermatology service in the Northern Territory (NT). Prescription of biologic therapies (BT) in the NT is uniquely challenging, with remote populations carrying a high tropical disease burden. The aim of this audit is to examine the demographics and outcomes of patients on BT for dermatologic conditions. Methods: Retrospective case note review of patients receiving BT through the RDH Dermatology department between August 2021 and October 2023. Data analysed were demographics, location, dermatological diagnosis and serology status. Results: In this audit, 115 patients were included. Age range of 13–91 years, mean of 51.1 years (±14.7), 52 (45.2%) patients were female and 8 (7.8%) identified as First Nations Australian. A large geographical area was serviced, with a primary address between 1 and 1496 km from RDH. Eighteen patients (15.7%) have discontinued BT completely. There was a statistically significant relationship between cessation of BT and increased distance of primary residence from RDH (p < 0.0007). Eighteen patients (15.7%) required management of infections identified in opportunistic infection screening. These infections were strongyloidiasis, tuberculosis, melioidosis and hepatitis B. Conclusions: There is significant anxiety surrounding BT and tropical infections, including in returning travellers in southern Australian states. There has been particular interest in strongyloidiasis infection, as dupilumab acts on the Th2 immunity mechanism critical to parasitic infection response. This audit exhibits the unique experience of dermatological care in a tropical setting, demonstrating how BT can be used safely and how, when identified, these tropical infections can be successfully managed. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a monoclonal antibody used for the treatment of moderate/severe atopic dermatitis (AD). In recent years, several studies have confirmed the positive association between AD and overweight/obesity, and a report demonstrated the effect of weight reduction on the improvement of AD symptoms. Methods: The weight of 170 patients under treatment with dupilumab was recorded at baseline and after 48 weeks (T48). Clinical monitoring was mainly conducted using the Eczema Area and Severity Index (EASI). The study aimed to assess a possible correlation between the clinical outcome of dupilumab therapy and BMI. Results: Although not statistically significant, patients with a BMI < 25 have a higher EASI percentage improvement than patients with a BMI ≥ 25 at any time point, and the percentage of overweight and obese patients that does not reach EASI-75 at T48 is higher compared to normal-weight patients (13.5% vs. 5.9%). Despite this, in the multivariate regression analysis, no baseline characteristic, including BMI, appears to increase the risk of not reaching EASI-75. In addition, the results show no differences in BMI between baseline and T48 in any age/sex group. Conclusions: The results suggest that overweight and obese patients have a lower response to dupilumab when considering the EASI score, but this difference does not appear to be clinically significant. Furthermore, dupilumab treatment does not seem to impact weight. [ABSTRACT FROM AUTHOR]

Summary: Background: The introduction of biologic therapies and the 'treat‐to‐target' treatment strategy may have changed the disease course of ulcerative colitis (UC). Aims: To describe the early disease course and disease outcome at 1‐year follow‐up in a population‐based inception cohort of adult patients with newly diagnosed UC. Methods: The Inflammatory Bowel Disease in South‐Eastern Norway (IBSEN) III study is a population‐based inception cohort study with prospective follow‐up. Patients newly diagnosed with inflammatory bowel disease during 2017–2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1‐year follow‐up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1‐year follow‐up. Results: We included 877 patients with UC (median age 36 years (range: 18–84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left‐sided colitis and 36.0% extensive colitis. At the 1‐year follow‐up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid‐free clinical remission was observed in 76.6%, and steroid‐free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. Conclusion: In this population‐based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1‐year follow‐up. The use of biologic therapy increases, consistent with findings from previous studies. [ABSTRACT FROM AUTHOR]

Introduction: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables. Aim: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay. Methods: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication. Results: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12–37] days (infliximab, 19 [13–33] days; adalimumab, 10 [5–26] days; vedolizumab, 21 [14–42] days; and ustekinumab, 21 [14–42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval. Conclusion: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval. [ABSTRACT FROM AUTHOR]

An interview with Isaac Eliaz, founder of Amitabha Medical Clinic in Santa Rosa, California, is presented. Eliaz talks about his training and education in Chinese medicine and the factors that influence his decision to become a licensed acupuncturist. He discusses his research on the protein called galectin-3 and its role in affecting cancer metastasis, sepsis and sepsis-associated acute kidney disease, as well as the ketogenic diet and intermittent fasting, and the development of apheresis.

Psoriatic arthritis (PsA) is part of the psoriatic disease spectrum and is characterized by a chronic inflammatory process that affects entheses, tendons and joints. Cytokines produced by immune and non-immune cells play a central role in the pathogenesis of PsA by orchestrating key aspects of the inflammatory response. Pro-inflammatory cytokines such as TNF, IL-23 and IL-17 have been shown to regulate the initiation and progression of PsA, ultimately leading to the destruction of the architecture of the local tissues such as soft tissue, cartilage and bone. The important role of cytokines in PsA has been underscored by the clinical success of antibodies that neutralize their function. In addition to biologic agents targeting individual pro-inflammatory cytokines, signaling inhibitors that block multiple cytokines simultaneously such as JAK inhibitors have been approved for PsA therapy. In this review, we will focus on our current understanding of the role of cytokines in the disease process of PsA and discuss potential new treatment options based on modulation of cytokine function. [Display omitted] • Cytokines such as TNF and IL-23 play a crucial role in the pathogenesis of psoriatic arthritis. • Several preclinical studies indicate that inhibition of cytokine function by neutralizing antibodies can suppress disease activity. • Neutralizing antibodies targeting these cytokines have been approved for clinical therapy of psoriatic arthritis. • JAK inhibitors that target multiple cytokine signaling events simultaneously have been approved for therapy of psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Objectives To investigate if disease activity among elderly RA patients >75 years of age has changed over time in the real-world clinical setting. Methods Data from an observational multicentre registry of RA patients in Japan were analysed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (>75 years) who achieved remission and low disease activity (LDA), from 2014 to 2021. The secondary outcome was to identify factors associated with remission and LDA by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression. Results A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients >75 years of age increased from 16.5% to 26.9%, with biologics and targeted synthetic DMARDs (b/tsDMARDs) use increasing and glucocorticoids use decreasing, while conventional synthetic DMARDs use remained relatively stable. The proportion of RA patients >75 years of age achieving remission and LDA significantly increased from 62.2% to 78.2% (P for trend < 0.001). A negative factor associated with achieving remission and LDA was glucocorticoid use, seropositivity and a history of previous b/tsDMARDs use while MTX use was associated positively, independent of other predictors. Conclusions In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

The article focuses on the transformative impact of orthobiologics in orthopaedic care, highlighting their role in enhancing natural healing processes and reducing the reliance on invasive surgeries and long recovery times. Topics include the wide-ranging applications of orthobiologics such as PRP, BMPs, and stem cell therapies in treating conditions like osteoarthritis, tendon injuries, and spinal disorders.

Introduction: Biologics like growth factors, stem cells, and platelet-rich plasma show potential in stimulating cartilage regrowth and reducing inflammation. By synthesizing preclinical and clinical studies, this study offers insights into how these biologics work and their effectiveness in treating knee osteoarthritis. Methods and Materials: Twenty-four participants with knee osteoarthritis (Kellgren − Lawrence grade II or III) were enrolled after obtaining consent. They received three doses of 2 ml intraarticular platelet-rich plasma at 1 month intervals. The clinical assessment involved the oxford knee score (OKS) and visual analogue scale (VAS) for pain on Days 0, 90, and 180. Ultrasound measured femoral and trochlear cartilage thickness pre- (Day 0) and post-PRP (Day 90–180). Results: Before treatment, the average pain score was 7.2 (p = 1.03). On Day 90 post-PRP, it decreased to 5 (p = 0.81), and by Day 180, it further reduced to 4.5 (p = 0.97). The initial total OKS was 33.5 (p = 1.76), which increased to 36 (p = 1.71) on Day 90 and 38.5 (p = 1.89) on Day 180. The femoral and trochlear cartilage thickness also showed improvement from baseline (0.92) to Day 90 (0.96) and Day 180 (1.01), indicating significant cartilage healing post-PRP administration. Conclusion: Our study highlights the probability of PRP in treating knee OA, highlighting their ability to alleviate symptoms, enhance joint function, and promote articular cartilage regeneration. [ABSTRACT FROM AUTHOR]

SUMMARY OF KEY POINTS: Asthma research and management needs to meet the priorities of the end user—patients, carers and clinicians.A better understanding of the natural history of asthma and the progression of disease has highlighted the importance of early identification of patients with asthma and the potential role of early intervention.Management of mild asthma requires a consistent approach with the same detail and consideration used when managing severe disease.Evidence around treatable traits approaches continues to evolve, supporting the role of a personalized medicine in asthma.Oral corticosteroid (OCS) stewardship continues to be an urgent issue in asthma management. Strategies to taper OCS doses and the implementation of biologic therapies for their steroid sparing benefits will be important steps to address this problem.The concept of remission in asthma provides an ambitious target and treatment outcome. [ABSTRACT FROM AUTHOR]

MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in healthy volunteers or in patients with psoriasis or rheumatoid arthritis (RA). This is the first study conducted under clinical practice conditions evaluating the switch from reference adalimumab to MSB11022 in patients with RA. Retrospective and multicenter study with data from the medical records of patients with RA who switched from reference adalimumab or another biosimilar to MSB11022 and maintained this treatment for at least 6 months. Information registered comes from baseline visit, the moment of the switch, and the follow-up visits. Data from 86 patients were evaluated (median age 63.5 years, 75.6% female, 44.2% had erosive RA). Only 3.5% of the patients received biologic therapy prior to adalimumab. At baseline, median DAS28-CRP was 1.77 (80.2% in remission and 96.5% with low disease activity) and median CDAI was 4.00 (44.2% in remission and 90.7% with low disease activity). After a median follow-up of 8 months, median DAS28-CRP was 1.87 (86.0% in remission and 94.2% with low disease activity) and median CDAI was 4.00 (38.5% in remission and 95.3% with low disease activity). Only three patients experienced pain, swelling, and stinging at the injection site or a locally extensive hematoma in the area of administration. Adalimumab biosimilar MSB11022 maintained the efficacy benefits provided by previous adalimumab treatments with a safety profile in line with that already described for other biosimilars. [ABSTRACT FROM AUTHOR]

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06–30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24–14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04–1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94–6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71–76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10−19–NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19–269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05–16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22–20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58–91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7–75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9–112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16–73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response. [ABSTRACT FROM AUTHOR]

Cancer cells depend on specific oncogenic pathways or present a genetic alteration that leads to a particular disturbance. Still, personalized and targeted biological therapy remains challenging, with current efforts generally yielding disappointing results. Carefully assessing onco-target molecular pathways can, however, potently assist with such efforts for the selection of patient populations that would best respond to a given drug treatment. RNF43, an E3 ubiquitin ligase that negatively regulates Wnt/frizzled (FZD) receptors by their ubiquitination, internalization, and degradation, controls a key pathway in cancer. Recently, additional target proteins of RNF43 were described, including p85 of the PI3K/AKT/mTOR signaling pathway and protease-activated receptor 2 (PAR2), a G-protein-coupled receptor that potently induces β-catenin stabilization, independent of Wnts. RNF43 mutations with impaired E3 ligase activity were found in several types of cancers (e.g., gastrointestinal system tumors and endometrial and ovarian cancer), pointing to a high dependency on FZD receptors and possibly PAR2 and the PI3K/AKT/mTOR signaling pathway. The development of drugs toward these targets is essential for improved treatment of cancer patients. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting about one-third of individuals with psoriasis. Defining axial involvement in PsA (axPsA) remains debated. While rheumatologists guide clinical practice, consensus on axPsA is still lacking. This paper explores historical and upcoming definitions from the Axial Involvement in Psoriatic Arthritis (AXIS) study, which aims to establish a validated axPsA definition. Epidemiological data reveal diverse axPsA prevalence rates, emphasizing its complex relationship with peripheral arthritis and enthesitis. Unique genetic, clinical, and radiological features differentiate axPsA from ankylosing spondylitis (AS), necessitating refined classification criteria. The recommendations from the Assessment of Spondylarthritis international Society (ASAS) provide valuable guidance due to the limited direct evidence. Emerging therapies, including interleukin-23 (IL-23) inhibitors or Janus kinase (JAK) inhibitors, are under investigation for axPsA. Currently, secukinumab, an interleukin-17 (IL-17) inhibitor, is an evidence-based option for axPsA management. However, given the variability in individual patient responses and disease manifestations, personalized, evidence-based treatment approaches remain essential for optimizing patient outcomes. In the final section, two real-life cases illustrate the challenges in managing axPsA, emphasizing the importance of tailored therapies. Achieving precision in defining axPsA remains a formidable task, making detailed criteria essential for effective strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. 'As needed' biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited. Objectives The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an 'as needed' approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care. Methods We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on 'as needed' biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis. Results Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of 'as needed' biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of 'as needed' drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9–64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8–33)]. Both patients and clinicians felt that an 'as needed' treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an 'as needed' approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence. Conclusions These data indicate that 'as needed' biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an increasingly prevalent immune‐mediated disease that leads to chronic changes in the oesophagus. These changes can include strictures, narrowing, and stenosis, mediated by an interleukin (IL)‐13 pathway, which leads to remodelling and fibrosis through increasing migration of fibroblasts and subepithelial fibrosis via collagen deposition 1. IL‐13 downregulates TSPAN12, a gene whose expression regulates fibrosis and causes changes in barrier function and higher rates of fibrostenosis in EoE. Dupilumab, a biologic therapy aimed at blocking IL‐13, has been shown to improve EoE‐related inflammation and fibrosis in clinical trials. We report here four unique patients with documented oesophageal stenosis with inability to pass a paediatric endoscope due to structuring disease, requiring dilation, who had resolution of their oesophageal narrowing following dupilumab therapy. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinits is a prevalent condition, affecting a substantial proportion of the population. This study investigates the impact of ongoing biologic therapy, specifically with Dupilumab, on allergy diagnostics in patients with allergic rhinits. Methods: Various tests, including the Skin Prick Test, serum IgE levels and Allergy Screening Panels, were examined for their effectiveness in detecting sensitizations during biologic treatment. Results: The results indicate a significant decline in total IgE levels following biologic therapy initiation, aligning with previous findings on Dupilumab's inhibitory effects on IL-4 and IL-13. However, the specific IgE to total IgE ratio for major allergens was not significantly reduced. Comparing diagnostic tools, the Skin Prick Test demonstrates an impressive retention rate of sensitizations (98%) during Dupilumab treatment, outperforming the Allergy Screening Panel, which shows a 75% detection rate. Notably, the panel displays limitations in capturing lower sensitization levels. Conclusion: In summary, this study underscores that, despite the influence of biologic therapy on certain markers, standard allergy tests remain viable while emphasizing the importance of considering specific IgE levels rather than relying solely on CAP classes. The Skin Prick Test in particular proves to be a reliable tool for identifying sensitizations during Dupilumab treatment. The results offer valuable guidance for the diagnostic management of Allergic rhinits in individuals subjected to Dupilumab treatment. [ABSTRACT FROM AUTHOR]