Expert Review of Clinical Immunology最新文献

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. High proportions of patients with CRSwNP characterized by type 2 inflammation fail to gain adequate control with conventional medical and surgical approaches. The application of biologics in clinical practice and assessments of novel biologics in clinical trials are blooming in expectations to fulfill the unmet medical needs of patients with CRSwNP with type 2 inflammation.

Areas covered: After an extensive search of PubMed, Medline, and EMBASE for the most recent evidence, we thoroughly summarize the current advances in biological therapies for treating patients with CRSwNP.

Expert opinion: In recent years, biological therapy has been in the spotlight in clinical studies on CRSwNP. Biologics have proven to be efficacious in reducing nasal polyp size, alleviating CRSwNP-related symptoms, improving quality of life, and reducing the need for systemic corticosteroids or endoscopic sinus surgery for nasal polyps. The considerable efficacy and safety profile of biologics demonstrated in clinical trials has offered patients with refractory CRSwNP another treatment option. However, some concerns remain to be addressed. Aspects such as the position of biological therapy in the management of CRSwNP, traits of patients suitable for certain biologics, etc. necessitate efforts to elucidate these unknowns in order to provide patients with tailored therapy.

Introduction: In recent years, the understanding of atopic dermatitis (AD) pathogenetic mechanisms has expanded, and now it is recognized that Th2 immune axis dysregulation is pivotal to AD pathogenesis. The advent of biological drugs and small molecules has marked a revolution in the treatment of AD. Dupilumab, targeting IL-4 and IL-13, has been the first to demonstrate efficacy in treating moderate to severe AD by modulating type-2 inflammation pathways. Increasing knowledge of different immune axis and cytokines has fueled the development of new biologics and small molecules. JAK inhibitors, which target the JAK-STAT pathway, involved in cytokine signaling, represent a promising novel therapeutic strategy, enlarging the treatment options for moderate to severe atopic dermatitis.

Areas covered: This comprehensive review aims to provide an updated and critical overview of the drugs currently in use and under investigation for the treatment of moderate to severe AD in children and adolescents, along with addressing the unmet needs and future research perspectives.

Expert opinion: Biologics and small molecules offer the promise to enlarge the arsenal options for the treatment of AD. Since the patients' response to biologics depends on AD pheno-endotype, choosing the right biologic is crucial for ensuring therapy success.

Background: CT-P47 is a candidate tocilizumab biosimilar that is currently in clinical development. We assessed the usability of CT-P47 self-administration via auto-injector (AI) in patients with rheumatoid arthritis (RA).

Research design and methods: This was a 12-week, single-arm, open-label, multiple-dose, Phase 3 study. Patients self-injected CT-P47 (162 mg/0.9 mL) via AI at Weeks 0 and 2, and then every other week via pre-filled syringe (PFS) from Week 4 through Week 10. The primary endpoint was POST-Self-Injection Assessment Questionnaire (SIAQ) at Week 2. Efficacy, safety, and immunogenicity were also assessed.

Results: Thirty-three patients were enrolled. Mean scores for all POST-SIAQ domains at Week 2 exceeded 8, except for 'self-confidence' (7.11) and 'satisfaction with self-injection' (7.98), indicating positive patient experiences with CT-P47 AI. Furthermore, an observer-completed checklist found that all patients successfully followed the required steps for self-injection. Efficacy, assessed by Disease Activity Score in 28 joints and its components, showed improvements from baseline to Week 12. No new safety signals were observed; the most common adverse events were leukopenia, neutropenia, and injection-site reaction, each occurring in 3 (9.1%) patients.

Conclusions: CT-P47 self-administered using an AI showed successful usability in patients with moderate-to-severe RA.

Trial registration: ClinicalTrials.gov identifier: NCT05725434.

Introduction: Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies against hemidesmosomal proteins on basal membrane zone. The presence of a high incidence of thrombotic events has led to the identification of a hypercoagulable state in BP patients.

Area covers: This review highlights the interactions between coagulation and immune-inflammatory responses based on the current literature available, as well as individual changes of characteristic coagulation parameters in BP. This review is based on publications up to August 2024 that were retrieved by a selective search in the PubMed database.

Expert opinion: The hypercoagulable state and bullous pemphigoid (BP) have a reciprocally enhancing effect on each other. For clinicians, it is crucial to closely monitor the fluctuations in circulating coagulation markers among BP patients, such as D-dimer, fibrinogen, and fibrin degradation products (FDP). Furthermore, considering the interplay between coagulation and immune-inflammatory responses in BP, targeting the shared pathways in treatment strategies could be beneficial for patients who exhibit both BP and a hypercoagulable state.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are severely immunocompromised and susceptible to bacterial, viral, and fungal infections. Despite improved anti-microbial prophylaxis and preemptive strategies, bacterial bloodstream infections (BSIs) occur frequently in allo-HSCT recipients and are associated with increased morbidity and mortality. Cytomegalovirus (CMV) and Epstein Barr virus (EBV) are the most relevant viruses following allo-HSCT and remain major concerns. Fungal infections, including those caused by Candida and Aspergillus species, are persistent and feared complications.

Areas covered: We aim to provide clinicians caring for allo-HSCT recipients with a comprehensive overview of the risk factors that predispose patients to common bacterial, fungal, and viral infections during the first years post-transplant. The focus is on the value of noninvasive diagnostic biomarkers and serological assays in enhancing the early detection and management of these infections.

Expert opinion: Effective management of infectious complications following allo-HSCT relies on continuous immune recovery monitoring and the implementation of advanced diagnostic methods. Utilizing noninvasive diagnostic methods is crucial for early detection and different intervention strategies. The development and integration of reliable microbiological markers into clinical practice is essential for enhancing patient outcomes and mitigating infection-related risks. Emphasizing diagnostic innovation will be pivotal in advancing patient care post-allo-HSCT.

Introduction: The clinical benefits of combining immunotherapy with chemotherapy and surgical resection in pancreatic adenocarcinoma remain unclear. The expression and clinical significance of HIF1A in circulating tumor cells (CTCs) in pancreatic adenocarcinoma remains limited.

Methods: This retrospective cohort study compared survival outcomes in pancreatic adenocarcinoma patients treated with two regimens: surgery+chemotherapy (nab-paclitaxel plus gemcitabine)+anti-PD1 (Tislelizumab) (S+AG+anti-PD1) (n = 37), and surgery+chemotherapy (S+AG) (n = 5). The study also evaluated CTCs and HIF1A-positive CTCs as potential prognostic biomarkers.

Results: The S+AG+anti-PD1 group (n = 37) showed significantly better progression-free survival (PFS) compared to S+AG (n = 15) in multivariate analysis (HR: 0.426, 95% CI: 0.185-0.983, p = 0.045). Overall survival (OS) differences were not statistically significant between groups. Lower CTC counts (≤1) were associated with longer PFS in surgical patients. This association was confirmed in multivariate analysis, after adjustment for AJCC stages (HR: 0.318, 95% CI: 0.104-0.974, p = 0.045). HIF1A-positive CTCs showed similar trends and prognostic significance to total CTC counts. Advanced AJCC stages remained the strongest independent predictor of worse PFS and OS.

Conclusion: Combining surgery, chemotherapy, and immunotherapy may improve PFS in resectable pancreatic adenocarcinoma. While CTCs and HIF1A-positive CTCs may have prognostic value, AJCC staging remains the most reliable indicator.

Objectives: Atopic/allergic diseases impose a growing burden on public health, affecting millions of patients worldwide. The main objective of this study was to develop a national expert consensus on relevant clinical questions related to type 2 inflammation.

Methods: We conducted: a comprehensive literature review with a qualitative analysis to identify the most repeated themes on the overlap of conditions; a modified 3-round Web-Delphi (or e-Delphi); and a final online decision conference.

Results: We included 51 studies. Following three Web-Delphi rounds, we ended up with 30 statements with a 76% overall full agreement rate, 16% agreement, 2% disagreement, and 0% full disagreement. The decision conference enabled adjustments, and the expert panel agreed unanimously on the final set of statements. The consensus used evidence synthesis, Web-Delphi, and decision conference to produce 30 statements on type 2 inflammation as a driver for multimorbidity in asthma, certain rhinitis phenotypes, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis grouped under five domains in underlying pathophysiology, multimorbidity, diagnosis and management, multidisciplinary management, and impact on mental health.

Conclusion: We expect the first Portuguese expert consensus INFLAT2-PT to promote understanding of type 2 inflammation diseases, multidisciplinary care, integrated care pathways, future research, and inform health authorities.

Introduction: The pathogenesis of inflammatory bowel disease (IBD) involves the dysregulation of multiple inflammatory pathways. The understanding of these mechanisms allows their selective targeting for therapeutic purposes. The discovery of Tumor Necrosis Factor-alpha's (TNF-α) role in mucosal inflammation ushered an exciting new era of drug development which now comprises agents targeting multiple pro-inflammatory signaling pathways, integrins, and leukocyte trafficking regulators.

Area covered: This review provides an overview of the main molecular players of IBD, their translation into therapeutic targets and the successful development of the advanced agents modulating them. We combine basic science with clinical trials data to present a critical review of both the successful and failed drug development programs. A PubMed literature search was conducted to delve into the available literature and clinical trials.

Expert opinion: The treatment landscape for IBD has rapidly expanded, particularly with the development of biologics targeting TNF-α, integrins, and S1P modulators, as well as newer agents such as IL-12/IL-23 inhibitors and JAK inhibitors, offering robust efficacy and safety profiles. However, challenges persist in understanding and effectively treating difficult-to-treat IBD, highlighting the need for continued research to uncover novel therapeutic targets and optimize patient outcomes.

Introduction: Depression and anxiety are among the most prevalent mental health conditions in Brazil. Both are associated with poor quality of life (HRQoL) and challenges in disease management for chronic illnesses, including Behçet's disease (BD). This study aimed to evaluate depression, anxiety, and HRQoL in BD patients from a non-endemic area.

Research design and methods: This case-control study included adult BD patients from Brazilian tertiary center and healthy controls (HC). All patients fulfilled the ISG and ICBD diagnostic criteria. Depression, anxiety and quality of life were assessed using BDI, HADS, SF-36, and physical capacity with the HAQ.

Results: We enrolled 58 BD patients (60% female, mean age 46.1) and 96 HC (74% female, mean age 44). High rates of depression and anxiety were observed in BD patients, correlating with disease activity, younger age, absence of a partner, shorter disease duration, and lower income. BD patients showed significant HRQoL restrictions, particularly in physical and emotional roles, compared to HC. Longer disease duration was correlated with better HRQoL.

Conclusion: High rates of depression and anxiety were observed in BD patients, negatively impacting HRQoL, particularly in those with higher disease activity. Further study and clinical attention are warranted to enhance patient care and outcomes.

Introduction: Current medications for autoimmune disorders often induce broad-ranging side effects, prompting a growing interest in therapies with more specific immune system modulation. Pioglitazone, known for its anti-diabetic properties, is increasingly recognized for significant immunomodulatory potential. Beyond its traditional use in diabetes management, pioglitazone emerges as a promising therapeutic candidate for autoimmune disorders.

Areas covered: This comprehensive review explores pioglitazone's impact on four prominent autoimmune conditions: systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. We focus on pioglitazone's diverse effects on immune cells and cytokines in these diseases, highlighting its potential as a valuable therapeutic option for autoimmune diseases. Here we have reviewed the latest and most current research literature available on PubMed, based on research published in the last 15 years.

Expert opinion: Pioglitazone as an immunomodulatory agent can regulate T cell differentiation, inhibit inflammatory cytokines, and promote anti-inflammatory macrophages. While further clinical studies are needed to fully understand its mechanisms and optimize treatment strategies, pioglitazone represents a potential therapeutic approach to improve outcomes for patients with these challenging autoimmune conditions. The future of autoimmune disease research may involve personalized treatment approaches, and collaborative efforts to improve patient quality of life.