Triplet therapy with androgen deprivation therapy (ADT), docetaxel, and androgen receptor pathway inhibitors (ARPIs), either darolutamide or abiraterone, is one of the standard treatments for metastatic hormone-sensitive prostate cancer (mHSPC); however, no randomized trial has directly compared both ARPIs within this regimen. Given practical and financial constraints, a head-to-head randomized trial directly comparing these ARPIs may be unlikely. To compare the real-world effectiveness of darolutamide- versus abiraterone-based triplet therapy in patients with mHSPC. Retrospective cohort study using a multinational electronic health record network. We conducted a retrospective cohort study using the TriNetX research network. Patients with mHSPC treated with darolutamide- or abiraterone-based triplet therapy were identified and balanced using propensity-score matching. The primary outcome was overall survival (OS), and the secondary outcome was time to next treatment (TTNT), defined by treatment switch. Prespecified subgroup analyses focused on age, cardiometabolic comorbidities, and polypharmacy-related medication use. Among 1607 eligible patients, 1252 were included after propensity score matching (626 per group). Darolutamide-based triplet therapy was associated with longer OS compared with abiraterone (hazard ratio (HR) 0.42). A favorable difference in TTNT was also observed (HR 0.66). These associations were consistent across clinically relevant subgroups, including patients aged ⩾65 years and those with ischemic heart disease or diabetes mellitus. In polypharmacy-enriched subgroups, darolutamide-based therapy was consistently associated with more favorable OS and TTNT. In this large real-world analysis, darolutamide-based triplet therapy was associated with longer OS and TTNT compared with abiraterone-based triplet therapy in patients with mHSPC, particularly among older individuals and those with comorbidities. These findings are hypothesis-generating, suggesting that ARPI selection within triplet therapy may have clinically relevant implications, supporting the need for prospective studies. Comparing two three-drug treatment options for advanced prostate cancer: results from a large real-world study Advanced prostate cancer is often treated with a combination of three drugs: hormone therapy, chemotherapy, and a hormone-blocking medicine. Two commonly used hormone-blocking drugs are darolutamide and abiraterone. Although both are recommended treatments, no clinical trial has directly compared these two options when used together with chemotherapy. In this study, we used a large international health database to compare these two treatment approaches in real-world clinical practice. We included over 1,200 patients and used statistical methods to make the two groups as similar as possible. We found that patients treated with darolutamide lived longer and had a longer time before needing another treatment compared with those treated with abiraterone. These benefits were also seen in older patients and in those with other medical conditions, such as heart disease or diabetes. However, because this was not a randomized clinical trial, other factors that we could not fully measure may have influenced the results. In addition, the follow-up period was relatively short. Overall, our findings suggest that darolutamide may be a more effective option than abiraterone when used as part of three-drug therapy for advanced prostate cancer. Further studies are needed to confirm these results.
Severe forms of alopecia areata (AA) often require off-label systemic treatments (ST) for which data on effectiveness and safety are limited. This study aimed to provide a comprehensive real-world overview of ST patterns in children with severe AA. We conducted a retrospective, longitudinal, multicenter study of children with AA (aged <18 years) receiving at least one ST (2010-2023), identified using a keyword search in Ouest Data Hub Warehouse (a hospital data network in France with a critical mass of 5.1 million patients) or by members of the Société Française de Dermatologie Pédiatrique. The primary outcome was drug survival (DS), defined as time on ST, and the secondary outcomes included reasons for treatment discontinuation and long-term observations. Among the 262 included children (median age at AA onset: 9 years; 58.4% girls, atopic dermatitis in 32.4%), the first-line ST most frequently initiated (median age: 12 years, alopecia totalis in 28.6%) was intravenous corticosteroids (35.9%, median duration: 3 months), followed by methotrexate + intravenous corticosteroids (24.0%, 12.5 months), oral corticosteroids (17.9%, 1 month), methotrexate (10.7%, 9.5 months), methotrexate + oral corticosteroids (8.8%, 9 months), and lastly baricitinib (2.7%, 2.5 months). Specific maintenance treatments were not significantly associated with DS. Psychological impact, atopic dermatitis, later childhood onset and female sex were associated with longer first-line systemic treatment drug survival. Treatment failure was the main reason for discontinuation (51.9%) and no serious adverse events were reported. Five years after starting the first ST (n = 62), 14.5% of patients had achieved remission. In this national, retrospective real-world study, drug survival analyses highlighted two treatment profiles: pulse therapy (corticosteroids) for flare-ups and maintenance treatments (methotrexate, baricitinib) for long-term management. Overall, the effectiveness of therapies appears limited with frequent relapse and a likely need for prolonged treatment. However, data on long-term treatment outcomes of JAKi in children are lacking. This study provides real-life data which could help improve management strategies in children with severe AA. Alopecia areata is a common chronic disease causing hair loss. Severe forms often require systemic treatments, for which data concerning efficacy and safety are limited. This study aimed to provide an overview of systemic treatment patterns in children with severe alopecia areata in France. We conducted a retrospective study using medical records from west regional French hospitals or obtained by members of the Société Française de Dermatologie Pédiatrique. We analyzed how long treatments were continued and the reasons why they were discontinued. A total of 262 children (58.4% girls) treated with at least one systemic treatment between 2010 and 2023 were included. Intravenous corticosteroids were the most frequently prescribed first-line systemic treatment (35.9%, median duration: 3 months), followed by methotrexate combined with intravenous corticosteroids (24.0%, 12.5 months), oral corticosteroids (17.9%, 1 month), methotrexate alone (10.7%, 9.5 months), methotrexate combined with oral corticosteroids (8.8%, 9 months), and baricitinib (2.7%, 2.5 months). The type of maintenance treatment was not significantly associated with treatment duration. Psychological impact, atopic dermatitis, later onset and female sex were associated with longer treatment duration. Treatment failure was the main reason for discontinuing treatment (51.9%); no serious adverse events were reported. Five years after starting the first systemic treatment, 14.5% of children with available data had achieved remission. Systemic treatment use could be categorized into pulse therapy (corticosteroids) for flare-ups and maintenance treatments (methotrexate and baricitinib) to maintain hair regrowth. This study provides real-life data which may help improve treatment strategies in children with severe alopecia areata.
Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have been approved for HER2-mutant NSCLC, real-world outcome data especially in the second-line setting remains limited. This non-interventional study utilized the Center for Cancer Genomics and Advanced Therapeutics national database to identify patients with HER2-mutant NSCLC who received second-line treatment in Japan. The primary objective was to characterize this population. Secondary objectives included describing second-line treatments and clinical outcomes (overall response rate [ORR], disease control rate [DCR], time on treatment [ToT] and reasons for second-line treatment termination). Among 3012 NSCLC patients identified, 168 (5.6%) had a HER2 mutation. In all NSCLC and HER2-mutant patients, median age was 66.0 years; 38.1% and 53.6% were female; 68.2% and 42.3% had a history of smoking; and 25.8% and 31.0% had brain metastases. In HER2-mutant patients, use of molecular targeted therapy (MTT, 44.6%) and chemotherapy (36.9%) as second-line treatment were comparable, followed by immunotherapy (15.5%), and immunochemotherapy (3.0%). Overall, median ToT with second-line treatment was 4.8 months (95% CI: 4.1-6.2). The longest median ToT was observed with MTT (8.1 months, 95% CI: 4.8-9.7), followed by chemotherapy (3.9 months, 95% CI: 2.5-5.2), immunochemotherapy (3.2 months, 95% CI: 0.4-not reached) and immunotherapy (5.5 months, 95% CI: 3.8-8.5). The ORR was 33.1% (95% CI: 25.4-41.6) and DCR was 78.4% (95% CI: 70.6-84.9). MTT was the most common second-line treatment, however, outcomes were generally poor, emphasizing the unmet need for effective second-line treatments for HER2-mutant NSCLC.
Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) offer new and potent options for curing for curing hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer; however, comparisons in terms of their relative effectiveness and safety concerns are lacking. We conducted a network meta-analysis (NMA) and a real-world study (RWS) to comprehensively evaluate these agents and validate clinical trial findings in routine practices. A Bayesian NMA of randomized controlled trials (RCTs) published up to November 2024 comparing ADCs with treatment of the physician's choice (TPC) was performed. Progression-free survival (PFS), overall survival (OS), tumor response rates, and grade ≥3 treatment-related adverse events (TRAEs) were obtained. Additionally, real-world survival data from our center [2013-2024] regarding T-DXd and SG usage were analyzed and compared with RCT results. Three RCTs involving 1,643 patients were included. Compared with TPC, ADCs significantly improved PFS [hazard ratio (HR) =0.51, 95% credible interval (CI): 0.36-0.72] and OS (HR =0.75, 95% CI: 0.65-0.86). Probability rankings favored T-DXd for PFS and SG for OS. ADCs significantly increased objective response rate (ORR) and clinical benefit rate (CBR) (P<0.05). Although ADCs showed marginally higher grade ≥3 adverse events (AEs), the lowest rate among ADCs was shown by T-DXd, while SG had the highest. In the RWS (n=22), T-DXd demonstrated a significantly longer average PFS compared to SG (5 vs. 2 months, P=0.008), consistent with RCT trends. ADCs significantly improved the clinical outcomes of patients with HR+/HER2 low expression advanced breast cancer. Compared with other ADC drugs, T-DXd showed relatively better treatment characteristics, better PFS benefit, and relatively low incidence of serious AEs (SAEs). Combined with RCTs and real-world data, T-DXd has potential advantages in this population.
Older adults represent most patients with cancer worldwide, yet they remain substantially underrepresented in randomized clinical trials (RCTs), limiting the evidence available to guide treatment decisions in this growing population. Real-world data (RWD), defined as data routinely collected from clinical practice such as electronic health records, administrative claims, clinical registries, wearable devices, and patient-reported outcomes, offer an opportunity to complement traditional trial evidence. In this narrative review, we aimed to synthesize the potential benefits, limitations, and considerations in leveraging RWD for clinical decision making in geriatric oncology. When analyzed rigorously, RWD can generate real-world evidence (RWE) that reflects the heterogeneity of patients seen in routine care and provides insights into treatment patterns, safety, effectiveness, healthcare utilization, and patient-centered outcomes. In geriatric oncology, these data sources are particularly valuable for capturing multidimensional health profiles that extend beyond chronological age, including comorbidities, functional status, and social determinants of health. RWD can also help characterize healthcare trajectories, identify predictors of treatment tolerance and toxicity, and evaluate outcomes such as quality of life and resource utilization. However, important challenges remain, including issues related to data quality and standardization, confounding and bias inherent to observational analyses, ethical considerations surrounding data sharing, and difficulties integrating RWE into clinical decision making. Advances in artificial intelligence, global data networks, regulatory acceptance of RWE, decentralized clinical trials, and expanded data infrastructure may further enhance the role of RWD in oncology. When used rigorously, RWE can help fill evidence gaps and support more personalized care for older adults with cancer.
Psoriasis is an immune-mediated chronic skin disease associated with multiple extracutaneous comorbidities, causing a severe quality of life impairment, whose treatment with risankizumab, a humanized anti-IL-23 monoclonal antibody, is very effective, with good safety profile and long-term outcomes. However, prescription in a real-world setting is conditioned by local health care system constraints, as the proven ineffectiveness or appearance of adverse events to first-line drugs. Such delay and selection of multi-failure patients might affect efficacy and outcomes. A prospective multicenter study, approved by the Ethical Independent Committee of AOU Cagliari, acronym ESSOS-BIO-PSO, Prot N° 2023/2532, was conducted to evaluate risankizumab's effectiveness and safety in Sardinian psoriasis centers over 6, 12, and 24 months. 73 patients with moderate-to-severe psoriasis treated with risankizumab over at least 6 months were recruited, predominantly male (70%) with a median age of 50 years and a median disease duration of 22 years. Most patients had extensive, difficult-to-treat areas involved, psoriasis arthritis and other comorbidities. Prior treatments included traditional systemic therapies and biologics (60%). At week 52, 74% achieved PASI-90, increasing to 76.7% at week 104, with all initial PASI-90 responders maintaining the response. Faster and sustained responses were observed in biologic-naïve patients and those with shorter disease duration. The difference between groups was statistically significant at week 16 (Mann-Whitney P=0.042), identifying naïve patients as "super-responders." No severe adverse events occurred; risankizumab was well tolerated and adherence was 100%. This real-world study investigates effectiveness and safety of Risankizumab in a population with a distinctive historical and genetic background, as well as environmental factors which may influence disease patterns and response to treatments. This first Sardinian study confirms durable results with excellent adherence in moderate-to-severe psoriasis patients, regardless of prior treatments and comorbidities burden, although in biologic-naïve patients the response is quicker.
In rheumatoid arthritis (RA), some patients experience joint pain that is disproportionate to the number of swollen joints, known as disproportionate articular pain (DP). This study aimed to clarify the prevalence and persistence of DP and to compare the outcomes across biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). From the ANSWER cohort in Japan, 5489 RA patients who initiated b/tsDMARDs between January 2010 and June 2024 were screened. DP was defined as having at least seven more tender joints (TJC) than swollen joints at baseline, and 432 patients met this criterion. Persistence of DP at 3 and 6 months was evaluated. Comparative analyses were conducted across mechanisms of action (MOAs): tumour necrosis factor-α inhibitors (TNFi), cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), interleukin-6 inhibitors (IL-6i), and Janus kinase inhibitors (JAKi). DP was identified in 7.8% of RA patients. At 3 months, DP persisted in 40.7% (TNFi), 36.5% (CTLA4-Ig), 48.0% (IL-6i), and 54.4% (JAKi). At 6 months, corresponding rates were 43.8%, 38.7%, 49.3%, and 61.1%. Multivariate analysis showed that higher TJC and previous treatment with two or more b/tsDMARDs were associated with persistent DP, whereas higher C-reactive protein was protective. Within JAKi, baricitinib showed lower DP persistence compared with other JAKi. DP was present in approximately 8% of RA patients. Persistent DP was associated with higher TJC, greater number of previous b/tsDMARDs, and lower inflammation. No MOA was clearly superior; however, baricitinib may confer a relative benefit within the JAKi class.
Friedreich ataxia is a multi-system neurodegenerative disorder with frequent cardiac and metabolic involvement. Omaveloxolone, the first approved therapy for Friedreich ataxia, improves neurological outcomes through nuclear factor erythroid 2-related factor 2 activation and exerts measurable systemic effects. However, its effects on lipid metabolism have not been systematically assessed. The present study aimed to systematically evaluate the longitudinal effects of omaveloxolone on serum lipid parameters in a real-world cohort of patients with Friedreich ataxia over a 12-month observation period. We conducted a retrospective, single-center, real-world observational study in adults with genetically confirmed Friedreich ataxia newly treated with omaveloxolone (150 mg/day). Serum lipid parameters, including total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, very low-density-lipoprotein cholesterol, triglycerides, C-reactive protein, apolipoprotein A-I, and apolipoprotein B (ApoB), were measured at baseline and after 1, 2, 3, 6, and 12 months. Longitudinal changes were analyzed using frequentist and Bayesian linear mixed-effects models. A total of 17 patients were included in the analysis (13 male [76%]; mean age 36.1 years [range 20-55]; mean disease duration 17.4 years [range 6-33 years]). Total cholesterol increased shortly after treatment initiation and remained elevated throughout the follow-up period, driven almost entirely by a sustained rise in low-density lipoprotein-cholesterol (+ 35-50 mg/dL) and ApoB (+ 20-25 mg/dL) levels, whereas high-density lipoprotein-cholesterol, apolipoprotein A-I, very low-density-lipoprotein cholesterol, and triglyceride levels remained stable. Low-density lipoprotein-cholesterol and ApoB levels were strongly correlated at all timepoints (r = 0.83-0.95). The total cholesterol/high-density lipoprotein-cholesterol ratio increased by approximately one unit and persisted throughout the follow-up period. In this real-world Friedreich ataxia cohort, omaveloxolone treatment was associated with a sustained shift toward a more atherogenic lipid profile, driven almost entirely by increased low-density lipoprotein-cholesterol and ApoB levels. This pattern is consistent with impaired hepatic clearance of ApoB-containing particles rather than increased production, supporting routine lipid monitoring and further evaluation of long-term cardiovascular risk.
Androgen receptor pathway inhibitors (ARPIs) and docetaxel are established first-line treatment options for metastatic hormone-sensitive prostate cancer (mHSPC); however, no randomized head-to-head trials have directly compared these strategies. We aimed to evaluate the efficacy of ARPI versus docetaxel as first-line treatment in patients with mHSPC. We retrospectively analyzed 148 patients with mHSPC treated with either ARPI (abiraterone, enzalutamide, or apalutamide) plus androgen deprivation therapy (ADT) (n = 98) or docetaxel plus ADT (n = 50). The primary endpoints were radiological progression-free survival (rPFS) and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were assessed using univariate and multivariate Cox regression analyses. At a median follow-up of 56.2 months, ARPI-based therapy was associated with significantly longer rPFS compared with docetaxel (median 68.6 vs. 18.9 months, p < 0.001). This rPFS benefit was consistent across subgroups defined by age, disease risk, disease volume, and visceral metastasis status. In multivariate analysis, ARPI treatment remained an independent predictor of prolonged rPFS (HR = 0.36, 95% CI = 0.23-0.58, p < 0.001). In contrast, OS did not differ significantly between the two treatment groups (median 79.8 vs. 62.2 months, p = 0.392), with no significant subgroup differences observed. In this real-world cohort, ARPI-based therapy was associated with an improvement in rPFS compared with docetaxel, while OS outcomes remained comparable. In the absence of direct randomized comparisons, these findings may provide supportive real-world evidence for the clinical relevance of ARPI-based therapy as a first-line treatment option for patients with mHSPC. Prostate cancer is called metastatic when it spreads to other parts of the body. In this stage, patients are usually treated with hormone therapy combined with either chemotherapy (docetaxel) or newer hormonal drugs called androgen receptor pathway inhibitors (ARPIs). However, there are no direct studies comparing these treatments. In this study, we analyzed 148 patients who received either ARPI-based therapy or docetaxel as their first treatment. ARPI-based therapy was associated with a longer time before the disease worsened, while overall survival was similar between the groups. Similar findings were observed across different clinical groups, such as age and disease burden. Due to the retrospective nature of the study, the results should be interpreted with caution. Larger prospective studies with higher patient numbers are needed to confirm these findings.
Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis of TA, JAK inhibitors (JAKi) could represent a viable therapeutic alternative. This study assessed the effectiveness of JAKi in patients with relapsing TA within a real-world setting in a country with a low incidence of TA such as Spain and included a comprehensive review of the literature. Methods: we conducted a retrospective analysis of TA patients managed with JAKi for recurrent disease across three Spanish centers. Evaluated outcomes comprised clinical remission, clinical and analytical remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A systematic literature search was performed to identify further cases of TA treated with JAKi. Results: six patients (83.3% females) with a mean age 48.5 years and relapsing TA received JAKi therapy: baricitinib (n = 2); tofacitinib (n = 2), and upadacitinib (n = 2). Before JAKi therapy, all (100%) patients had received conventional synthetic immunosuppressants, and four (66.7%) biologics. Clinical remission was achieved in 2/6 (33.3%), 3/5 (60%), 3/5 (60%), 2/3 (66.7%), and 2/2 (100%) patients at 1, 3, 6, 12 and 18 months, respectively. Clinical + analytical remission was observed in 1/6 (16.7%), 2/5 (40%), 2/5 (40%), 2/3 (66.7%), and 2/2 (100%) patients, respectively. Two patients who underwent a follow-up PET/CT imaging showed partial improvement in both. After a median (IQR) follow-up of 9.5 (6.0-16.7) months, one (16.7%) patient discontinued the initial JAKi due to no improvement and one patient discontinued it because was diagnosed with tonsillar neoplasia. The literature search identified another 166 JAKi-treated TA cases with clinical improvement reported for the majority of them. Conclusions: this real-world analysis and literature review suggest that JAKi could be effective in the management of TA, including for those patients who have failed established glucocorticoid-sparing strategies.
Vericiguat and sacubitril/valsartan both modulate the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling pathway and may improve myocardial function in patients with heart failure. To compare the effects of vericiguat, sacubitril/valsartan, and their combination on left ventricular function and clinical outcomes in heart failure with nonpreserved ejection fraction patients. In this retrospective real-world study, patients were classified into three groups: vericiguat added to guideline-directed medical therapy (vericiguat group), sacubitril/valsartan-based therapy (sacubitril/valsartan group), and combined sacubitril/valsartan plus vericiguat therapy (add-vericiguat group). Changes in left ventricular ejection fraction (ΔLVEF), in stroke volume (ΔSV), and in log-transformed N-terminal pro-B-type natriuretic peptide (ΔLog10 NT-pro BNP) from baseline to 1 year were evaluated. Clinical outcomes were also assessed. At 1 year, LVEF significantly improved in both the vericiguat group (p = 0.02) and the sacubitril/valsartan group (p < 0.001). There was no significant difference in ΔLVEF between these two groups (p = 0.25). In contrast, the add-vericiguat group demonstrated a significantly greater improvement in ΔLVEF compared with the vericiguat group (p = 0.01). In a real-world setting, vericiguat was associated with improvements in left ventricular function comparable to those of sacubitril/valsartan, and combination therapy provided incremental benefits. Vericiguat may serve as an alternative or adjunctive treatment option, particularly in patients unable to tolerate or maintain angiotensin receptor-neprilysin inhibitor therapy.
The expanding use of biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) has substantially improved outcomes in autoimmune diseases but is accompanied by complex safety concerns. Risk management plans (RMPs) have been introduced to mitigate treatment-related risks; however, real-world adherence to these strategies and their broader clinical impact remain incompletely characterized. We conducted a retrospective observational cohort study of adult patients with autoimmune diseases who received bDMARDs, tsDMARDs, or biosimilars at a tertiary medical center in southern Taiwan between October 2014 and December 2023. Patients were classified into RMP and non-RMP groups based on completion of predefined pre-treatment safety assessments within 6 months prior to therapy initiation, including pulmonary and tuberculosis evaluation, viral hepatitis screening, and documentation of cardiovascular and malignancy risk factors. Clinical outcomes included Pneumocystis jirovecii pneumonia (PJP), major adverse cardiovascular events (MACE), treatment-related respiratory adverse events, and all-cause mortality. Multivariable logistic regression and time-to-event analyses were performed to evaluate associations between RMP implementation and clinical outcomes. Among 1,078 patients included, only 348 (32.3%) fulfilled the predefined RMP criteria prior to treatment initiation. Compared with the RMP group, patients without RMP exhibited significantly higher incidences of PJP (11.9% vs. 2.3%), MACE (8.5% vs. 2.6%), treatment-related respiratory adverse events (50.4% vs. 42.8%), and all-cause mortality (7.3% vs. 1.7%) (all p < 0.05). After multivariable adjustment, RMP implementation remained independently associated with lower risks of PJP (adjusted odds ratio [aOR] 0.18, 95% CI 0.15-0.84), MACE (aOR 0.30, 95% CI 0.13-0.71), and all-cause mortality (aOR 0.21, 95% CI 0.07-0.61). Subgroup and time-to-event analyses demonstrated that anti-CD20 therapy was associated with the highest risk of early-onset PJP, MACE, and mortality, with most events occurring within the first three to six months following treatment. In real-world clinical practice, adherence to predefined RMPs prior to targeted therapy initiation is suboptimal and is strongly associated with clinically meaningful differences in infectious, cardiovascular, and survival outcomes. These findings suggest that RMP implementation is associated with benefits extending beyond infection prevention and underscore the importance of standardized, consistently applied risk management strategies, particularly for high-risk targeted therapies such as anti-CD20 agents. Key Points • Adherence to predefined risk management plans (RMPs) before initiating biologic or targeted synthetic DMARDs remains suboptimal in real-world practice. • Implementation of RMPs is associated with lower risks of Pneumocystis jirovecii pneumonia, major adverse cardiovascular events, and all-cause mortality. • Lack of structured pre-treatment safety assessment may contribute to early severe complications after therapy initiation. • Anti-CD20 therapy is associated with a higher risk of early adverse outcomes, underscoring the need for careful risk stratification and monitoring.
Predicting difficult-to-manage (D2M) axSpA remains challenging, as both inflammatory and non-inflammatory factors contribute to treatment failure. Functional impairment captured by Health Assessment Questionnaire-Disability Index (HAQ-DI) and Multidimensional Health Assessment Questionnaire (MDHAQ) may provide additional predictive value, but are rarely evaluated in this context. To assess the predictive value of HAQ-DI and MDHAQ for identifying patients at risk of D2M axSpA in real-world clinical practice. Single-center retrospective observational study based on data from a clinical registry. The study included patients with axSpA initiating biologic or targeted synthetic disease-modifying antirheumatic drugs. Data included demographic, clinical, and laboratory parameters, as well as patient-reported outcomes. D2M status was defined according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Health status was evaluated using HAQ-DI and MDHAQ. Logistic regression identified predictors of D2M status at baseline, 24 and 48 weeks. The cohort included 300 treatment courses in 217 patients (average age 45 years, 49% female, 83% HLA-B27 positive, 83% r-axSpA). At baseline, 11% patients met ASAS criteria for D2M axSpA, decreasing to 8.8% at week 48. D2M patients were older (p = 0.03), exercised less frequently (p = 0.04) and had higher disease activity. In multivariable models, baseline HAQ-DI independently predicted D2M status at baseline (OR 3.29, p = 0.008) and week 24 (OR 4.56, p = 0.005) and functional dimension of MDHAQ at week 24 (OR 3.47, p = 0.039). Functional impairment, reflected by higher HAQ-DI and MDHAQ scores, was the strongest predictor of D2M axSpA and may serve as a valuable tool for identifying these patients early and addressing nonpharmacological management strategies ahead. Everyday functioning helps predict which patients with axial spondyloarthritis will have difficult-to-manage disease Axial spondyloarthritis (axSpA) is a long-term inflammatory rheumatic disease that mainly affects the spine and causes pain, stiffness, and reduced mobility. Some patients respond well to treatment, while others continue to experience troublesome symptoms even when receiving innovative drugs such as biologic or targeted synthetic. If two or more of such therapies fail, these patients are described as having difficult-to-manage (D2M) axSpA. Being able to identify such patients early may help doctors provide better care and distinguish between the true need of modification of pharmacotherapy or rather addressing other aspects of the disease, such as pain and functional decline due to causes not related to inflammation. In this study, we followed adults with axSpA who were receving biologic or targeted synthetic treatments. We collected clinical information, laboratory results, and patients’ own reports about how their symptoms affect daily activities. Two questionnaires “HAQ-DI” and “MDHAQ” were used to measure everyday functioning, such as the ability to dress, stand, walk, or complete routine tasks. We found that patients with D2M axSpA had worse functional limitations from the beginning and throughout treatment, even though inflammation markers in blood tests were similar to other patients. Higher HAQ-DI and MDHAQ scores strongly predicted which patients would continue to struggle during treatment. These findings suggest that assessing everyday functioning “not only inflammation” can help identify people who may need additional support. Early use of exercise programs, physical therapy, and personalized care strategies could improve outcomes for these patients.
Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of NTRK fusion-positive tumors. Although its efficacy has been demonstrated in clinical trials, particularly in infantile fibrosarcoma (IFS), real-world data in pediatric populations remain limited. We conducted a prospective observational study within the SACHA- France study, including patients < 25 years treated with larotrectinib outside clinical trials between April 2019 and September 2025. Clinical characteristics, molecular data, treatment indications, responses, survival outcomes, toxicity, treatment discontinuation, and resistance were analyzed. Twenty-five patients were included (median age 2.8 years): IFS (n = 9), extra-CNS tumors (n = 10) and CNS tumors (n = 6). Twelve patients were treated at progression, nine to avoid mutilating surgery, two for multifocal/metastatic disease, and two as maintenance for high relapse risk; five received upfront larotrectinib. The overall response rate was 70% (95% CI: 47-87), with a median time to best response of 2 months. Two-year event-free and overall survival rates were 61.3% (95% CI: 38.3-77.7) and 74.9% (95% CI: 52.4-87.9) respectively. A trend toward higher 2-year EFS was observed in IFS versus CNS tumors (72.9% [95% CI: 26.7-92.9] vs 33% [95% CI: 10.5-80]). Treatment-related adverse events were reported in 8% of patients. Disease progression occurred in five patients, with acquired resistance mutations in the kinase domain confirmed in two. Larotrectinib shows meaningful efficacy and favorable tolerance across NTRK fusion-positive malignancies beyond IFS. These real-world data support early molecular testing, highlight histology-dependent outcomes, and inform clinical management strategies.
Before the advent of neoadjuvant immunotherapy (IO) in macroscopic disease, IO and targeted therapies were recommended as adjuvant therapies for the treatment of stage III resectable melanoma. However, real-world evidence on their use and outcomes remains limited. This study described treatment patterns and survival outcomes among patients with stage III resectable melanoma who received adjuvant therapy in France. This retrospective cohort study used data from the exhaustive French national health data system (SNDS) to identify adults initiating adjuvant nivolumab (NIVO), pembrolizumab (PEM), or dabrafenib-trametinib (DT) between January 1, 2019, and December 31, 2021. Patients were followed until December 31, 2023, or death. Exclusion criteria included prior metastatic disease, other active cancers, or prior use of study drugs. Outcomes included treatment patterns at recurrence, described using Sankey diagrams, and survival (recurrence-free survival [RFS], overall survival [OS]), assessed using a Kaplan-Meier estimator. The study population consisted of 2612 patients with resected stage III melanoma initiating an adjuvant therapy. Of them, 1483 (56.8%) received NIVO, 635 (24.3%) had PEM, and 494 (18.9%) had DT. Median (Q1-Q3) age was 64.0 (52.0-73.0) years for NIVO, 64.0 (51.0-74.0) years for PEM, and 58.0 (46.0-70.0) years for DT. Median follow-up was 39.5 months for NIVO, 38.9 months for PEM, and 36.9 for DT. At 36 months, RFS (95% CI) was 50.7% (48.0%-53.2%) for NIVO, 52.7% (48.6-56.7%) for PEM, and 48.3% (43.7-52.7%) for DT. Finally, 36-month OS (95% CI) was 81.8% (79.7-83.8%) for NIVO, 82.3% (79.0-85.2%) for PEM, and 74.4% (70.1-78.2%) for DT. Immunotherapy represented 75% of therapies at recurrence among patients with adjuvant NIVO/PEM and 55% among patients with adjuvant DT. Immunotherapy is the cornerstone of adjuvant and recurrence treatment in stage III melanoma, representing the vast majority of adjuvant therapies and recurrence therapies. Despite effective therapies, recurrence remains frequent, with around half of relapses at 3 years, underscoring the need for continued optimization of treatment strategies.
Rheumatoid arthritis (RA) management emphasizes treat-to-target strategies with timely escalation from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to biologic (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) when remission or low disease activity is not achieved. Comparative real-world effectiveness evidence across advanced therapies remains limited in some settings. To compare 12-month outcomes and treatment persistence across biologic (bDMARD) and targeted synthetic DMARDs (tsDMARDs) in Saudi patients enrolled in the Rheumatoid Arthritis Saudi Database (RASD). We conducted a prospective multicenter cohort study of RASD patients receiving biologic or targeted synthetic DMARDs, with a minimum follow-up of 12 months and assessments at baseline, 3-6 months, and 12 months. Outcomes included longitudinal DAS28-CRP change, 12-month disease activity, function, fatigue, remission, and treatment persistence through 36 months. Analyses used mixed-effects, covariate-adjusted regression, ordinal regression, logistic regression, and Kaplan-Meier methods, as appropriate for each outcome. We analyzed 647 treatment courses across nine advanced therapies. Disease activity improved significantly over time, with a strong overall DAS28-CRP time effect (p<0.0001), but no significant overall drug effect (p=0.327) or time-by-drug interaction (p=0.218). Model-estimated 12-month DAS28-CRP values were closely clustered across therapies, with overlapping confidence intervals and no significant pairwise differences. In adjusted 12-month analyses, DAS28-CRP, CDAI, fatigue severity, and remission were comparable across agents. Most adjusted between-drug comparisons were non-significant, except for worse HAQ category with certolizumab compared with tofacitinib (adjusted OR 2.45, 95% CI 1.12-5.37). Remission varied significantly across participating centers. Discontinuation rates were low, most commonly due to lack of efficacy, and treatment persistence did not differ significantly across therapies through 36 months (log-rank p=0.17). Advanced RA therapies were associated with significant disease activity improvement and minimal adjusted between-drug differences. Except for an isolated worse HAQ signal with certolizumab versus tofacitinib, outcomes were broadly comparable across agents. Center-level remission variation highlights the importance of standardized treat-to-target implementation. ClinicalTrials.gov Identifier: NCT06417138.
China's hospital-integrated Internet Hospital model embeds virtual outpatient care within hospital information systems, pharmacy workflows, and regulatory oversight structures. However, encounter-level evidence on real-world utilization, operational efficiency, online prescribing, and repeat use remains limited. The objective of this study is to describe the first-year utilization, service efficiency, prescribing safety, and continuity-of-care potential of a hospital-integrated Internet Hospital in Henan province, China. We conducted a retrospective observational study of all online consultation orders generated from November 1, 2023, to October 31, 2024, at a large tertiary hospital. Deidentified data from consultation logs, prescribing modules, and pharmacy systems were descriptively analyzed. Key measures included order outcomes, consultation type and modality, patient-level repeat use, response time, online prescribing, prescription review outcomes, and ratings. A total of 90,006 online consultation orders were generated; 54,389 (60.4%) were completed, 32,720 (36.4%) were cancelled, and 2,897 (3.2%) expired because payment was not completed. Most cancellations occurred before physician acceptance. Text-based consultations accounted for 83,833 orders (93.1%). Virtual Consultations accounted for 78,313 orders (87.0%) and did not permit prescribing; Virtual Follow-up Consultations accounted for 11,693 orders (13.0%) and had a higher completion rate (74.3 vs. 58.4%). Among 49,724 unique patients, 16,554 (33.3%) generated two or more orders. Median response time was 93.4 minutes (interquartile range: 12.4-345.5). Prescriptions were generated in 491 orders (0.55%); 359 patients paid for medication orders, and 118 prescriptions required physician modification after initial automated review. No legally restricted controlled drugs were prescribed online. Ratings were submitted for 5,820 orders (6.5%). The platform primarily served as a hospital-governed digital entry point for consultation and triage, with a controlled follow-up pathway for selected prescription renewal. It demonstrated feasibility but also highlighted preacceptance cancellations, long-tailed response times, limited older-adult use, and expert-heavy workload as priorities for optimization.
Acute non-large-vessel occlusive ischemic stroke (ANLVOIS) is a common subtype of stroke. The core of treatment is to rapidly improve cerebral perfusion and reduce neurological injury. Aspirin is used in the acute phase, but its efficacy is limited in some patients. Tirofiban (a highly selective glycoprotein IIb/IIIa receptor antagonist) is widely used and there are few direct comparative studies of its efficacy and safety with those of the other drugs. To compare the clinical efficacy and safety of the antiplatelet drugs tirofiban and aspirin in the treatment of ANLVOIS. This retrospective controlled study collected clinical data of ANLVOIS patients from Wuqiao County People's Hospital (Jan 2023-Dec 2024), grouped by treatment: Group A (n=55, aspirin alone) and Group B (n=58, tirofiban bridging to aspirin). NIHSS scores (pre-treatment, 1 week, and 3 months post-treatment) were analyzed for neurological function, and 3-month mRS scores were analyzed for prognosis. 90-day all-cause mortality, symptomatic intracranial hemorrhage (sICH) incidence and adverse event rate were compared. Statistical analyses were performed using SPSS 26.0. Baseline characteristics were balanced between the two groups (P>0.05). At 7 days and 3 months post-treatment, NIHSS and mRS scores decreased significantly in both groups (P<0.05), with Group B having notably lower scores than Group A (P<0.05). The 90-day all-cause mortality, sICH incidence and adverse event rates were 1.7%, 3.4%, and 6.9% in Group B, respectively, compared with 3.6%, 5.5%, and 16.4% in Group A, with no significant intergroup differences (P>0.05). In this retrospective analysis, early treatment with tirofiban followed by aspirin was associated with better neurological and functional outcomes in ANLVOIS than aspirin alone, while maintaining a comparable safety profile. These real-world findings support the use of tirofiban-based induction as an effective acute-phase antiplatelet strategy.
Drug development for Alzheimer's disease (AD) remains challenging, with only a 0.4% success rate from Phase I trials to regulatory approval. Drug repositioning leverages existing approved drugs to identify promising drug alternatives, particularly when combined with real-world data (RWD) and target trial emulation. In this study, we comprehensively screened 1,241 approved drugs using a large-scale Japanese claims database (n = 2,090,465; 2005-2023). We identified patients newly prescribed a study drug and applied an active-comparator, new-user design. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the covariates. The primary outcome was incident AD, defined using ICD-10 codes (F00 and G30). We estimated cumulative incidence using IPTW-adjusted Kaplan-Meier analysis and Cox proportional hazards models and conducted sensitivity analyses using Fine-Gray competing risk models, empirical calibration with negative control outcomes, and E-value estimation. We performed in vitro validation using Aβ-Tet-ON SH-SY5Y cells and quantified Aβ expression using western blotting. Benzbromarone, a uricosuric agent, was associated with a decreased risk of AD onset (adjusted HR: 0.54, 95% CI: 0.41-0.71, p < 0.05 post-FDR correction); this association remained robust across sensitivity analyses. In vitro, benzbromarone reduced Aβ protein expression in SH-SY5Y cells in a dose-dependent manner, even following transcriptional blockade, suggesting a posttranscriptional regulatory mechanism. In conclusion, using a combined approach of RWD-based pharmacoepidemiology and in vitro validation, we identified benzbromarone as a novel candidate potentially associated with reduced AD risk. Our findings highlight the potential of drug repositioning strategies to accelerate AD drug discovery, promoting further mechanistic and clinical investigations.
Clinical characteristics and outcomes of patients treated for dedifferentiated liposarcoma (DDLPS) at community oncology centers are not well studied. Our goal was to assess real-world patterns of diagnosis, clinical management, and outcomes of patients with DDLPS in US community settings. This was a retrospective observational study of electronic health records (EHRs) obtained from the iKnowMed EHR system for patients diagnosed with DDLPS between January 1, 2008, and October 31, 2023, within The US Oncology Network and non-Network practices. The primary outcomes were real-world overall survival (rwOS) from diagnosis and from the start of the first systemic therapy after documented metastatic disease (1L[M]) until death (due to any cause). Real-world progression-free survival (rwPFS) was assessed from 1L(M) systemic therapy initiation to the earliest date of progression or date of death (due to any cause). A total of 123 patients with DDLPS (women, 33.3%; White, 60.2%; metastatic disease, 34.0%) were included. Biomarker testing was most frequently performed for the MDM2 proto-oncogene (78.0%), followed by CDK4 (38.2%) and TP53 (10.6%). DDLPS treatments included surgery (76.0%), radiation therapy (35.0%), and systemic agents (46.3%), of which cytotoxic drugs, particularly first-line anthracycline, were the most common. Median rwOS was 44.2 months. For patients with metastatic disease, median rwPFS was 2.7 months, and rwOS from start of 1L(M) systemic therapy was 11.7 months. Patients with DDLPS treated in US community settings are heterogeneous in terms of demographic and clinical characteristics, biomarker testing, treatment, and outcomes. The relatively poor survival rates suggest an unmet need for better therapeutics.