Advances in Therapy最新文献

Introduction: Endoscopic assessment, routinely performed using the Rutgeerts score (RS), offers prognostic information for postoperative Crohn's disease (CD) patients. The clinical relevance of anastomotic lesions (AL), however, remains debated. Additional proposed scoring systems include the POCER index (PI) and the UEDA et al. score (US), which also characterize anastomotic and peri-anastomotic disease features. Our retrospective study aims to evaluate the predictive value of the PI and the US in a real-life cohort.

Methods: Consecutive patients with CD undergoing ileo-colonic resection with subsequent first endoscopic evaluation within 6-12 months after surgery were enrolled. Endoscopic recurrence (ER) was assessed by RS, PI and US. Clinical recurrence (CR) was assessed at 24 ± 3 months. A second endoscopy at 24 ± 3 months was available for some patients.

Results: A total of 177 patients were included. Regarding CR prediction, RS ≥ i2 showed an AUROC of 0.74 (sensitivity 82.7%, specificity 56.9%); PI ≥ 2 an AUROC of 0.61 (sensitivity 31%, specificity 82.5%); US ≥ intermediate an AUROC of 0.67 (sensitivity 50%, specificity 74.6%). In patients without ileal lesions at 6-12 months, RS ≥ i2 showed an AUROC of 0.68 (sensitivity 58.3%, specificity 75.8%), PI an AUROC of 0.67 (sensitivity 25%, specificity 92.6%) and the US ≥ intermediate an AUROC of 0.63 (sensitivity 16.7%, specificity 93.4%) for predicting CR. In the sub-cohort of patients with RS < i3 at 6-12 months, the PI showed an AUROC of 0.65 (sensitivity 21.4%, specificity 87.3%), while the US showed an AUROC of 0.53 (sensitivity 14.3%, specificity 82.6%) for CR.

Conclusion: Grading AL seems to improve the prognostic value of early endoscopic assessment in predicting postoperative clinical recurrence. Future prospective studies are required to validate these findings. Graphical Abstract available for this article. Postoperative recurrence is a prevalent issue in Crohn's disease, affecting patients' quality of life. The Rutgeerts score serves as the standard scoring system for assessing the presence and severity of endoscopic activity after surgery; however, it is often inaccurate, particularly in cases of mild inflammation or when inflammation is confined to surgical connection between two parts of the bowel (the anastomosis). This study investigated two alternative scoring systems: the POCER index and the score developed by Ueda et al. These tools offer a more comprehensive evaluation of the anastomotic area and have proven useful in predicting postoperative recurrence within 2 years post-surgery, especially when inflammation is restricted to the anastomosis. Integrating these newer scoring systems into routine clinical practice may facilitate earlier identification of patients at higher risk of recurrence, thereby aiding in the development of more personalized treatment strategies.

Introduction: Treatment for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has shifted from chemoimmunotherapy (CIT) to targeted therapies, administered as continuous treatment until progression or in fixed-duration regimens. Fixed-duration regimens with targeted therapies (usually in combination regimens with venetoclax and a Bruton tyrosine kinase inhibitor [BTKi] and/or an anti-CD20 monoclonal antibody) are of increasing interest, and recent phase 3 trial results support this approach. Fixed-duration treatment offers a pre-defined treatment stopping point and may provide patients with a treatment-free interval, potentially reducing the burden of long-term therapy while minimizing cumulative toxicity and costs.

Methods: Here, we review the currently approved fixed-duration regimens and some investigational combinations in ongoing registrational clinical trials.

Results: The registrational fixed-duration studies CLL14 (venetoclax plus obinutuzumab), GLOW (ibrutinib plus venetoclax), CAPTIVATE (ibrutinib plus venetoclax), AMPLIFY (acalabrutinib plus venetoclax with or without obinutuzumab), and MURANO (venetoclax plus rituximab) along with the investigator-initiated CLL17 study, which may impact treatment guidelines, demonstrated extended treatment-free intervals. Generally, targeted fixed-duration regimens in patients with unmutated immunoglobulin heavy chain variable region or TP53 and/or del(17p) demonstrated greater efficacy than CIT, but outcomes were typically poorer than in patients without these high-risk features. Cardiovascular toxicity and death remain a significant concern with ibrutinib plus venetoclax, which was also associated with high rates of diarrhea and atrial fibrillation.

Conclusion: Successful fixed-duration regimens in CLL should achieve deep remission (i.e., undetectable minimal residual disease), sustain long-term progression-free survival, decrease the burden of treatment-related adverse events, and allow for re-treatment with minimal risk of drug resistance. Although fixed-duration treatment represents a positive step forward for most patients with CLL/SLL, the currently approved regimens often fall short in patients at high risk of progression. Continued research and development of next-generation drugs is essential to enhance efficacy and safety, ultimately improving outcomes in all patients with CLL/SLL.

Background: Virtual reality (VR) technology has become more mature and accessible in recent years. In the context of alcohol use disorder (AUD), it can be used for various therapeutic contexts, such as exposure therapy, diagnostics, and improved interactivity. Although promising, the data regarding its effectiveness vary; therefore, caution is warranted when it is introduced. This review aims to illustrate the current state of research on virtual reality in alcohol use disorder therapy.

Methods: In accordance with the PRISMA and Cochrane guidelines, publications focusing on implementing virtual reality to treat alcohol use disorder, published since 2015, were investigated. These included trials, prototype presentations, and expert interviews.

Results: Thirty-two publications were identified, 19 of which were trials, with 653 participants. The results indicate that VR has been researched in various therapeutic contexts. In virtual cue-exposure therapy (CET), trials suggest that virtual reality can effectively increase craving and anxiety after one-time use and reduce craving after multiple uses. In diagnostics, trials demonstrate that it is possible to distinguish between heavy and light consumers based on the choices made in virtual reality, leading to a more standardized approach. In virtual approach-avoidance therapy (AAT), trials indicate increased effectiveness in the use of VR compared to the usual two-dimensional approach regarding craving. Non-trial publications focus on the inclusion of specific technologies, such as biofeedback, design choices, and ethical considerations.

Conclusions: Despite promising results, current research is limited. From a therapeutic perspective, the limitations are the variety of approaches to development and use, the heterogeneous designs, inconsistent trial results, and the lack of long-term data on abstinence, effectiveness, and potential risks for patients. Technologically, the adaptation of virtual environments and the inclusion of biofeedback devices require more research. Methodically, the interdependence of scientific disciplines increases the complexity. Since virtual reality has been used in other types of therapy with success (e.g., phobia and anxiety treatment) and a growing body of literature presents promising findings, there is a strong incentive to continue research on using virtual reality in treating alcohol use disorder.

Introduction: Gestational trophoblastic neoplasia (GTN) is a highly curable malignancy arising from placental trophoblasts, yet a small subset of patients develops multidrug resistance with limited therapeutic options. The discovery of high programmed death-ligand 1 (PD-L1) expression across trophoblastic tumors has provided a compelling biological rationale for immunotherapy, particularly immune checkpoint blockade targeting the PD-1/PD-L1 axis.

Objective: To summarize current evidence on immunotherapy in GTN, integrating biological foundations, clinical experiences, and ongoing clinical trials, and to discuss future perspectives toward individualized, fertility-preserving management.

Methods: A narrative review was conducted according to structured PRISMA-based principles. Literature was retrieved from PubMed, Scopus, and Web of Science from 2000 to 2025 using predefined descriptors related to GTN and immunotherapy. Eligible studies included clinical trials, case series, case reports, and translational research addressing immune checkpoint inhibitors in GTN.

Results: GTN exhibits high PD-L1 expression, mirroring the immune-privileged nature of the placenta. Checkpoint inhibitors alone, such as pembrolizumab, avelumab, or the combination of camrelizumab plus apatinib (that potently suppresses the kinase activity of vascular endothelial growth factor 2), have demonstrated complete and durable responses in approximately 70-80% of patients with multidrug-resistant GTN, with acceptable safety and preserved fertility.

Conclusions: Immunotherapy has expanded therapeutic GTN, transforming refractory disease as a result of its immune responsiveness. Checkpoint inhibition not only achieves high remission rates but also offers fertility preservation and long-term survivorship. The future challenge lies in optimizing combination strategies, refining biomarkers, and ensuring equitable global access to these emerging treatments.

Introduction: Hematologic response is well established in systemic light chain (AL) amyloidosis treatment, but hepatic response patterns remain unclear. This study explored hepatic response dynamics in hepatic-involved patients with AL amyloidosis who achieved hematologic partial response within 24 months post-treatment.

Methods: Using two- and four-level hepatic response criteria (two-level: hepatic organ response [hepatic OR], hepatic no response [hepatic NR]; four-level: hepatic complete response [hepaCR], hepatic very good partial response [hepaVGPR], hepatic partial response [hepaPR], hepatic no response [hepaNR]), responses were assessed at 3, 6, 12, and 24 months.

Results: Among 137 patients (median follow-up: 55.0 months), hepatic OR and ≥ hepaPR plateaued at 24 months, with hepatic OR achieved in 75.6% (65/86), hepaCR in 10.5% (9/86), hepaVGPR in 16.3% (14/86), and hepaPR in 38.4% (33/86). The two-level hepatic response better predicted overall survival than the four-level criteria. Patients achieving hepatic OR within 24 months had significantly better prognosis than non-responders (log-rank p = 0.008; HR, 2.782; 95% CI, 1.260-6.141), with no impact from response speed. Hematologic complete response (CR_H) at 3 months predicted higher likelihood of 24-month hepatic OR (OR 2.571, 95% CI, 1.387-4.767, p = 0.003).

Conclusion: The study highlights the importance of monitoring hepatic response dynamics, identifying 3-month CR_H and 24-month hepatic OR as key treatment milestones. A graphical abstract is also available with this article.

Introduction: Efsubaglutide alfa is a novel, long-acting GLP-1RA, which imparts human homology, molecular flexibility and enhanced GLP-1 receptor-specific binding. This drug-free, observational follow-up evaluated remission and durability of glycemic control in drug-naïve T2D participants who had completed 52 weeks of once-weekly efsubaglutide alfa in the SUPER-1 randomized trial.

Methods: Adults who completed SUPER-1 with HbA1c ≤ 7.0% discontinued all glucose-lowering therapy and entered a 52-week, medication-free observation. The primary endpoint was diabetes remission, defined as HbA1c < 6.5% (American Diabetes Association criteria, ADA 2021) measured ≥ 3 months after the last efsubaglutide dose. Kaplan-Meier (KM) analysis was employed to estimate the probability of maintaining HbA1c < 7% over 12 months post-treatment. Continuous glucose monitoring (CGM) assessed changes in time in range (TIR). Factors contributing to diabetes remission were analyzed using logistic regression and subgroup KM analyses.

Results: Twenty-nine participants were enrolled; at 3 months post-discontinuation, the diabetes remission rate was 60% (12/20). The probabilities of maintaining HbA1c < 7% at 6- and 12-month post-treatment were 58.1% (17/29; 95% CI 39.0-73.1%) and 41.4% (12/29; 95% CI 24.0-58.0%), respectively. Efsubaglutide alfa treatment during the 52-week period significantly improved TIR (baseline: 46.4%; 52 week: 89.1%, p < 0.001). TIR levels off therapy were 70.1% at 3 months, 68.1% at 6 months and 64.1% at 12 months. Patients who achieved remission had relatively lower baseline HbA1c and higher body mass index (BMI) values before treatment, demonstrating significantly greater reductions in waist circumference (- 3.3 cm) and postprandial glucose (PPG) levels compared to those who did not remit. Post-treatment HbA1c levels and improvements in homeostasis model assessment of β-cell (HOMA-β) scores were strongly associated with a higher probability of remission (p = 0.03 and 0.05, respectively). Body weight remained stable throughout the 12-month drug-free observation without rebound.

Conclusions: Efsubaglutide alfa demonstrated efficacy in achieving stable glycemic control and drug-free diabetes remission. Enhanced β-cell function emerged as a key factor contributing to long-term remission.

Trial registration: ClinicalTrials.gov identifier, NCT06605287.

Introduction: Type 2 diabetes mellitus (T2DM) presents a major challenge in low- and middle-income countries (LMICs) due to workforce shortages, limited primary-care capacity, and fragmented chronic-care delivery. Community-based diabetes care models have emerged as scalable approaches to strengthen self-management and extend service reach. With this background, we aimed to synthesize global evidence on community-based diabetes care models, classify major intervention typologies, examine their alignment with the diabetes care continuum, and assess their effectiveness and implementation characteristics.

Methods: A narrative review was conducted using a structured search of PubMed, Scopus, Web of Science, and Embase for studies published between January 2010 and March 2025. Eligible studies focused on community-based T2DM interventions delivered by community health workers (CHWs), peer educators, or digital-community hybrids. Interventions were categorized and mapped across the diabetes care continuum, and evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, as well as complementary integration models.

Results: Eleven studies were included, in which peer-led models were common in high-income countries, while CHW-led and hybrid models were predominant in LMICs. Interventions demonstrated clinically significant improvements in glycated hemoglobin (HbA1c), BMI, and self-efficacy. Successful models embedded within existing public health systems or culturally rooted community platforms showed higher adoption and long-term maintenance. Digital interventions enhanced reach, but faced challenges with sustained engagement and infrastructure support. The RE-AIM analysis revealed strong effectiveness and reach; however, long-term maintenance and adoption varied based on the level of contextual integration and supervision structures.

Conclusion: Community-based T2DM care models offer scalable, sustainable strategies to improve disease control. Integration into national health platforms, supportive supervision, and digital augmentation enhance implementation success. Challenges persist in follow-up, cost-effectiveness, and equity design; scale-up should prioritize integration, financing, and CHW capacity.

Introduction: While the therapeutic options for Crohn's disease (CD) have broadened swiftly, direct comparative evidence on treatment efficacy remains limited. This study explored the relative efficacy and safety of available treatments based on current evidence.

Methods: A network meta-analysis (frequentist random-effect model) evaluated comparative efficacy of licensed advanced therapies for CD using data on efficacy of maintenance therapy from fully published, randomised, controlled phase 3/3b studies with 48-64-week follow-up periods and placebo or active comparator controls, identified through a systematic literature review (PROSPERO number CRD42023413752). Intravenous (IV) and subcutaneous (SC) infliximab, SC adalimumab, IV and SC vedolizumab, SC ustekinumab, SC risankizumab, and oral upadacitinib were included. Clinical remission and endoscopic response rates attained through maintenance regimens were assessed according to line of use (e.g., first-line and second-or-later line). Safety (serious adverse event rates) was also compared.

Results: Data from nine randomised controlled trials were analysed. SC infliximab 120 mg every 2 weeks (q.2.w.) exhibited the highest risk difference (95% confidence interval) vs. placebo in both first-line and second-or-later-line maintenance treatment for achieving clinical remission (0.38 [0.23-0.53] and 0.51 [0.19-0.83], respectively; 14 and 12 comparator arms, respectively), and endoscopic response (0.39 [0.29-0.49] and 0.35 [0.07-0.63], respectively; 5 comparator arms) compared with other treatments. Differences between therapies did not reach statistical difference. Safety was comparable among treatments in terms of rates of serious adverse events.

Conclusions: The current NMA integrating recently updated phase 3 data in CD indicated that no single treatment significantly outperformed others in achieving clinical remission and endoscopic response, although SC infliximab 120 mg q.2.w exhibited highest numerical efficacy as both a first-line and second-or-later-line maintenance treatment in adult patients with moderate-to-severe CD.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment challenges. Although androgen deprivation therapy (ADT) has been the standard treatment for metastatic prostate cancer for over 80 years, its efficacy is often limited to the initial treatment phase for most patients. Recent clinical trials have investigated various therapeutic options for mCRPC; however, real-world evidence is essential for a comprehensive understanding of the current treatment landscape and to identify unmet clinical needs.

Methods: A multi-country, retrospective, non-interventional study was conducted across 31 centres in Latin America, the Middle East and Asia. Adults diagnosed with mCRPC between January 2016 and December 2018 were enrolled as the study subjects. Treatment patterns were thoroughly analysed, including those used when patients were at the metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC) settings.

Results: Among 795 enrolled patients with mCRPC (most aged ≥ 65 years), significant attrition was observed between treatment lines: approximately 50% of patients on first-line (1L) therapy advanced to second line (2L) but only 23.5% proceeded to third line (3L). New hormonal agent (NHA)-based therapies were the most prevalent choice for 1L and 2L, with post-chemotherapy NHA being the most common 1L-2L sequence. Disease progression, the primary reason for discontinuation across all regimens, occurred in > 60% of patients during mCRPC treatment. Generally, median real-world progression-free survival (rwPFS) decreased with each subsequent line of therapy. This study also highlights the inadequacy of prostate cancer screening in these regions.

Conclusion: This study offers valuable insights into the current treatment landscape of patients with mCRPC in non-US and non-European settings within a real-world context.

Clinicaltrials:

Gov id: NCT04801186.