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Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

INTRODUCTION: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. METHODS: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. RESULTS: Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. CONCLUSION: This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Background: To evaluate the overall satisfaction, device usability, and injection experience of MS patients self-administering ofatumumab using the Sensoready® autoinjector device in the United States (US). Methods: This US-based, cross-sectional survey study included patients with MS (≥ 18 years) who self-administered ofatumumab using the Sensoready device within the previous 12 months of the survey. Eligible patients were administered a 30-item de novo questionnaire that focused on overall device satisfaction, device usability, convenience/flexibility for travel with the device, user confidence, injection experience, and time to administer the injection. Ratings were measured on Likert and numeric rating scales, with higher scores indicating positive responses. Results: Overall, 105 patients with MS (disease-modifying therapy [DMT]-experienced: 65; DMT-naïve: 40) were included. The mean (standard deviation [SD]) age was 42.5 (12.2) years. The majority of patients (86.7%) expressed high satisfaction (i.e., rated either 4 [satisfied] or 5 [extremely satisfied] on a 5-point Likert scale) in study population. The overall mean (SD) satisfaction score with Sensoready device was 4.4 (0.7), with a higher device satisfaction reported in the DMT-experienced vs. DMT-naïve group (4.6 [0.66] vs. 4.1 [0.69]). A higher proportion of DMT-experienced patients reported high satisfaction scores as compared to DMT-naïve patients (90.8% vs. 80.0%). The most common reasons for high satisfaction included reasonable administration time (90.5%), overall ease of use (89.5%), a monthly dosing schedule of ofatumumab (89.5%), the time required for device preparation (86.7%), ease of device preparation (81.9%), device ergonomics (76.2%), and portability (73.3%). Regardless of prior DMT experience, the majority of patients felt confident to self-administer ofatumumab using the Sensoready device; moreover, the majority expressed their intention to continue with the Sensoready device and would recommend ofatumumab to others. Furthermore, 77.1% reported that the use of Sensoready device to self-administer ofatumumab was not found to interfere with their daily activities; patients reporting non-interference with their daily activities were higher in the DMT-experienced vs. DMT-naïve group (83.1% vs. 67.5%). Conclusions: Regardless of prior DMT experience, patients with MS report high satisfaction levels and positive experiences with the use of the ofatumumab Sensoready device in real-world practice, mostly driven by reasonable administration time and ease-of-use. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown efficacy in clinical trials for slowing chronic kidney disease (CKD) progression, but real-world data in diverse populations are limited. This retrospective study evaluated the effectiveness and safety of SGLT2i versus renin-angiotensin-aldosterone system (RAAS) blockade in CKD patients. Data from Ramathibodi Hospital (2010–2022) were analyzed, including 6,946 adults with CKD stages 2–4, with and without diabetes, who received SGLT2i (n = 1,405) or RAAS blockade (n = 5,541) for at least three months. Patients were matched 1:4 by CKD stage and treatment initiation date. A weighted Cox proportional hazards model with inverse probability weighting assessed the effect on composite major adverse kidney events (MAKEs), including eGFR decline ≥ 40%, progression to CKD stage 5, dialysis initiation, and cardiovascular or kidney death. SGLT2i therapy was associated with a lower risk of composite MAKEs (HR: 0.59; 95% CI: 0.36–0.98; P = 0.041) and less frequent progression to CKD stage 5 (HR: 0.52; 95% CI: 0.34–0.80; P < 0.003). Adverse event rates were similar between groups, with lower urinary tract infection incidence in the SGLT2i group. These findings suggest SGLT2i therapy might reduce adverse kidney outcomes in CKD patients, regardless of diabetic status, with a favorable safety profile. [ABSTRACT FROM AUTHOR]

AbstractPatients participating in clinical trials are highly selected and may not represent the general population. The pivotal study of teclistamab (MajesTEC-1), a B-cell maturation antigen (BCMA)xCD3 bispecific antibody, demonstrated impressive response rates and progression free survival in relapsed/refractory multiple myeloma (RRMM) with acceptable toxicity. We performed a retrospective study of 58 patients treated as standard of care at four US academic centers to determine how these results translated to the real-world. Most patients (87.9%) would not have been eligible for the MajesTEC-1 study due to either disease related factors, patient related comorbidities or socio-economic/geographical factors. Despite these ‘less-favorable’ characteristics we observed similar efficacy and toxicity to MajesTEC-1. A meta-analysis with six other published real-world series (n = 546) confirmed these results. These data support the significant clinical activity of teclistamab in RRMM and highlights the importance of real-world data to accompany the pivotal trial data to further inform daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Deutetrabenazine is a widely used drug for the treatment of tardive dyskinesia (TD), and post-marketing testing is important. There is a lack of real-world, large-sample safety studies of deutetrabenazine. In this study, a pharmacovigilance analysis of deutetrabenazine was performed based on the FDA Adverse Event Reporting System (FAERS) database to evaluate its relevant safety signals for clinical reference. Methods: Adverse events (AEs) of FAERS with deutetrabenazine as the primary suspect drug were collected from the first quarter (Q1) of 2017 to Q1 of 2024. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to mine AEs risk signals of deutetrabenazine. AEs were standardized and classified using the System Organ Class (SOC) and Preferred Terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) version 23.0. Results: A total of 3,583 AEs with deutetrabenazine as the primary suspect drug were collected in this study. We found that these AEs involved 23 SOCs, and the positive signals were mainly concentrated in systemic disease and various reactions at the site of administration (n = 1816, ROR = 1.23, PRR = 1.18, IC = 0.24, EBGM = 1.18), neurological disorders (n = 1736, ROR = 3.02, PRR = 2.60, IC = 1.38, EBGM = 2.60) and psychiatric disorders (n = 1,659, ROR = 4.15, PRR = 3.52, IC = 1.82, EBGM = 3.52). We eventually identified 100 valid PTs that met the criteria of the four algorithms. Drug ineffective, dyskinesia, depression, somnolence, suicidal ideation were considered to be the common PTs of deutetrabenazine. Tongue thrust (n = 4, ROR 253.47, PRR 253.35, IC 7.88, EBGM 235.95), grunting (n = 5, ROR 78.49, PRR 78.45, IC 6.26, EBGM 76.71) and drooling (n = 17, ROR 13.21, PRR 13.19, IC 3.72, EBGM 13.14) were not mentioned in the specification, but the high signal intensity suggested that they may be the potential adverse reactions. Conclusion: The efficacy of deutetrabenazine may be accompanied by some potential adverse effects in several systems. Adverse events in psychiatric, neurologic, gastrointestinal and respiratory need to be monitored in clinical practice. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to explore the efficacy and safety of belimumab among Chinese patients with SLE in a real-world setting. Methods A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from July 2021 to December 2022. Based on baseline characteristics, the patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group had experienced a severe flare. Refractory patients were patients with unsatisfactory GC taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled. Results A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3–18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SLE Responder Index 4 (SRI-4) response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Of the three groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased. Conclusion Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence indicating remarkable achievement of the SRI-4 response during belimumab therapy in newly diagnosed SLE patients. [ABSTRACT FROM AUTHOR]

Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression‐free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real‐world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18‐months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real‐world study recapitulate results from clinical trials including meta‐analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones. [ABSTRACT FROM AUTHOR]

[Display omitted] Extensive efforts have been put into reducing the heavy burden of esophageal squamous cell carcinoma (ESCC) in China. However, the joint impact of prevention and treatment on the long-term overall survival (OS) of ESCC patients remains largely unknown. We consecutively recruited 13,255 ESCC patients from two Chinese centers: the Northern center, located in a high-risk area with abundant screening programs; and the Southern center, situated in a non-high-risk area with improved clinical practices. Inter-center comparison, longitudinal intra-center comparison, and a simulation analysis were conducted to investigate the influence of tumor downstaging and high-quality clinical treatment on OS. During a follow-up period of 12.52 years, the Northern center exhibited higher median survival than the Southern center (6.22 vs. 3.15 years; HR adjusted = 0.73, 95% CI: 0.69–0.77). Mediation analysis demonstrated that its OS advantage was largely (77.7%) attributed to earlier TNM stage (stage 0–II: 51.3% vs. 24.6%). In temporal analyses, patient survival in the Southern center gradually improved (median survival during 2015–2018 vs. 2009–2014: 3.58 vs. 2.93 years; HR adjusted = 0.86, 95% CI: 0.79–0.94), coinciding with the progress of treatment-related indices (completeness of TNM staging in discharge diagnosis [from 53.7% to 99.6%], adoption of minimally invasive esophagectomy [from 0.0% to 51.1%] and right thoracic esophagectomy [from 12.4% to 86.4%], etc.). Simulation analysis further demonstrated that integrating both downstaging and high-quality treatment would lead to the best survival. Tumor downstaging and high-quality clinical treatment have a joint impact on ESCC patient survival. Establishing a comprehensive strategy that integrates cancer prevention with optimal clinical treatment is crucial for alleviating the ESCC burden. [ABSTRACT FROM AUTHOR]

The study examines the effectiveness of add-on therapy with SGLT2 inhibitors or GLP-1 receptor agonists in adults with type 1 diabetes using real-world data from the DPV registry. Results show improvements in HbA1c, systolic blood pressure, and cholesterol levels without increasing the risk of ketoacidosis or severe hypoglycemia. However, the clinical relevance of these improvements may be limited, and further research is needed to identify specific subgroups that may benefit from this therapy. The study highlights the need for larger, long-term studies to assess the efficacy of these treatments in type 1 diabetes. [Extracted from the article]

AbstractObjectiveMethodsResultsConclusion\nPLAIN LANGUAGE SUMMARYThis study aimed to describe clinical characteristics—including blood counts and pharmacologic cytoreductive treatment patterns—and outcomes after 6 months of hydroxyurea (HU) treatment among patients with polycythemia vera (PV) in US community practices.This retrospective observational study included adult patients with a PV diagnosis (1JAN2008–31JAN2020) and ≥2 postdiagnosis visits in the iKnowMed electronic health record database (US Oncology Network and non-Network clinics). Suboptimal HU response required ≥1 criterion after ≥3 months of treatment: white blood cell count (WBC) >10 × 109/L, platelet count >400 × 109/L, and/or hematocrit >45%. Patient characteristics were summarized from structured data using descriptive statistics; overall survival was assessed by Kaplan–Meier method.Among 5871 patients, mean age at diagnosis was 66.1 years (69.8% ≥60 years); 67.2, 59.4, 38.2, and 33.9% of patients had elevated hematocrit, hemoglobin, WBC, and platelets, respectively; 6.1% had a previous thrombotic event. Of 4185 (71.3%) high-risk and 1675 low-risk patients, 55.0 and 32.0% received pharmacologic cytoreductive treatment, most commonly HU (89.8 and 88.9%). After 6 months of pharmacologic cytoreductive treatment, 56.9% had a suboptimal response. Five-year survival probability was 81.5 and 84.3% among patients with suboptimal and optimal responses to HU, respectively, which was not statistically different but suggests potential for survival benefits with longer follow-up.Nearly half of high-risk patients with PV did not receive pharmacologic cytoreductive treatment. Of those who did, over half had suboptimal response, suggesting these patients may need dose adjustments, improved adverse effect management, or alternative treatments. Longer follow-up may be needed to assess an association between HU response and survival.Polycythemia vera (PV) is a rare blood cancer that causes an overproduction of blood cells. The aim of treatment is to reduce the number of blood cells and prevent blood clots. Hydroxyurea is a drug often used for treatment, but it does not work for all patients and the side effects can lead some patients to discontinue treatment. For this analysis, the authors looked at health records of almost 6000 patients with PV who were treated in community practices in the United States between 2008 and 2020. The study found that after 6 months of receiving hydroxyurea, blood cell numbers remained elevated in over half of the patients, indicating the treatment was inadequate. This finding suggests that patients with PV may need medication dosage adjustments, improved management of their treatment side effects, or alternative treatments sooner than is currently common. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations. Methods: We enrolled 41 mCRPC patients who received at least 1 month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes). The primary endpoint was imaging-based progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), PSA50 response, and adverse events (AEs). To ensure accurate research results and control confounding factors, we will employ multivariate Cox proportional hazards models to evaluate key variables affecting mCRPC patient survival outcomes. Results: This study enrolled 41 patients, 22 in Cohort A and 19 in Cohort B. The median PFS for all patients was 21.8 months, and the median OS had yet to be reached. The overall ORR was 48.8%, and the DCR was 61.0%. Specifically, the median PFS for Cohort A was 21.8 months compared to 14.5 months for Cohort B. The median OS had yet to be reached for either cohort. Regarding efficacy, 81.8% of patients in Cohort A and 73.7% in Cohort B achieved a PSA50 response. Imaging assessments showed ORRs of 54.6% for Cohort A and 42.1% for Cohort B, with DCRs of 72.7% and 47.4%, respectively. 85.4% of patients experienced grade 1 or 2 adverse events, and 51.2% encountered grade 3 or 4. In the multivariate Cox regression analysis focusing on PFS, the Gleason score was identified as a significant predictor (HR = 5.8, 95% CI: 1.65–20.2, p = 0.006). Conclusion: Combined first-line treatment with PARP inhibitors and NHT is effective and well-tolerated in mCRPC patients with HRR gene mutations, particularly those with BRCA1, BRCA2, or ATM mutations. These findings underscore the potential of this therapeutic combination in managing mCRPC in the Chinese population, suggesting a favorable outcome for those with specific genetic backgrounds. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has radically changed the management of many types of solid tumors including non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated that ICIs improve the survival and the quality of life of patients with advanced non oncogene NSCLC as compared to standard therapies. However, not all patients achieve a clinical benefit from this immunotherapeutic approach. As a result, real-word validation of the efficacy and safety of ICIs can be useful for defining potential predictive biomarkers as well as for overcoming limitations linked to clinical trial restrictions. Methods: We retrospectively retrieved the clinical data of patients with advanced non oncogene NSCLC treated with ICIs (anti-PD-1 or anti-PD-L1) as single agent or in combination with chemotherapy at "San Giovanni di Dio e Ruggi D'Aragona" University Hospital from January 2016 to December 2023. Potential correlations between clinical-pathological characteristics and safety or survival outcomes were investigated employing the Fisher's exact test, Mann-Whitney U test, the Kruskal-Wallis method and log-rank test, as applicable. Multivariate survival analyses were performed using the Cox proportional hazards model. Results: Clinical data of 129 patients were retrieved. At a median follow-up of 29.70 months, progression-free survival (PFS) and overall survival (OS) were 5.27 months and 8.43 months, respectively. At the multivariate analyses, smoking status, presence of bone metastases and the occurrence of immune-related adverse events (irAEs) were correlated with both PFS and OS. Moreover, patients treated with anti-PD-1-based therapy achieved an increased clinical benefit than those treated with anti-PD-L1. Discussion: In this study we described our real-world experience of ICIs for the treatment of patients with advanced non oncogene NSCLC. A decreased OS in our study population was reported as compared to that of patients included in the clinical trials. Noteworthy, correlations between clinical-pathological characteristics and survival outcomes emerged. Nevertheless, the potential integration of clinical-pathological characteristics as predictive biomarkers in more accurate therapeutic algorithms as well as the underlying biological mechanisms should be further validated in ad hoc studies. [ABSTRACT FROM AUTHOR]

Rationale Methods Results Conclusions Doravirine (DOR) is an attractive new option both for ART‐naïve people with HIV (PWH) and those with suppressed HIV‐RNA who seek treatment simplification. We used real‐world data to examine the pattern of use of DOR‐containing regimens in these settings.All PWH enrolled in the Icona cohort after January 2020 who initiated a three‐drug regimen (3‐DR) with DOR or an integrase inhibitor (INSTI)‐based regimen as first antiretroviral therapy (ART) or when switching ART, with HIV‐RNA ≤50 copies/mL, were included. We used univariate and multivariable logistic regression models to identify demographic factors, immuno‐virological and laboratory markers associated with the prescription of 3‐DR DOR instead of INSTI‐based regimens.A total of 5803 PWH were included; 1958 were in the first regimen (80 DOR, 1,878 INSTI) and 3854 (387 DOR, 3,458 INSTI) were ART‐experienced virologically suppressed. In the first line, 3‐DR DOR was more frequently started in people who inject drugs, and its use was also associated with higher body mass index, higher low‐density lipoprotein levels, and less advanced HIV disease compared with PWH initiating an INSTI‐based regimen. In the switch setting, older age, Italian origin, higher estimated glomerular filtration rate and aspartate aminotransferase levels were all strongly associated with 3‐DR DOR use, as well as higher a CD4/CD8 ratio (only vs. 3‐DR INSTI), while the association with lipid abnormalities was attenuated.Our analysis shows that among PWH in care in Italy, those with less advanced HIV disease but with other fragilities and potential risk factors for comorbidities are more likely to use DOR‐ than INSTI‐based regimens, regardless of prior treatment history. [ABSTRACT FROM AUTHOR]

Aim: Toripalimab is the first antitumor programmed cell death protein 1 (PD-1) antibody approved in China. For better patient management, it is important to understand the real-world outcomes of toripalimab in treating patients with lung cancer in the real world outside of clinical trials to improve patient care. Methods: We retrospectively examined the clinical data of 80 patients with lung cancer who received the PD-1 inhibitor (toripalimab). The Chi-square test was performed to identify clinical factors associated with the advancement of the disease. Multivariate Cox regression analysis was used to screen prognostic variables linked to real-world progression-free survival (PFS) and overall survival (OS). OS and PFS were calculated using the Kaplan-Meier method, and the comparisons were determined using the log-rank test, and continuous and categorical variables were explained using median and percentage, respectively. Result: The median OS of the estimated 80 patients was 15.85 months (95% confidence interval [CI]: 14.103–17.949 months), and the estimated PFS was 5.650 months (95% CI: 7.226–11.264 months). The longer OS and PFS correlate with the patient's staging and number of treatment lines. The PD-1 drug gave stage III patients a significantly longer PFS and OS compared to stage IV patients (PFS: 14.65 vs. 6.68, P = 0.004; OS: 21.1 vs. 13.7, P = 0.003). First- or second-line immunotherapy patients have significantly longer PFS and OS than third- or fourth-line (PFS: 6.4 vs. 3.6, P = 0.009; OS: 20.0 vs. 10.5, P = 0.003). In patients with stage IV (n = 60) with extensive metastasis, the site of metastasis is mostly 1–3 sites after receiving toripalimab. The duration of PD-1 inhibitor OS in progressive patients (n = 56) was significantly prolonged (P = 0.038). Conclusion: For patients with lung cancer, toripalimab can considerably extend PFS and OS in the first or second line and in stage III. PD-1 inhibitors are administered to patients with stage IV extensively metastatic lung cancer, which indicates an oligometastatic progression pattern, primarily in 1–3 locations, who are treated with PD-1 inhibitors. Continuing toripalimab beyond disease progression significantly prolonged OS. [ABSTRACT FROM AUTHOR]

Background & Aims: Pan-genotypic ribavirin-free oral direct-acting antivirals, including the glecaprevir/pibrentasvir combination, are recommended for the treatment of most patients with chronic hepatitis C virus (HCV) infection. In Romania, the HCV-infected patient population receiving glecaprevir/pibrentasvir is not well characterized and data on treatment effectiveness is lacking. The ODYSSEY study aimed to provide insights into the characteristics and treatment outcomes of HCV-infected Romanian patients receiving 8-week therapy with glecaprevir/pibrentasvir. Methods: This observational, retrospective medical chart review study was based on a Patient Support Program for HCV-infected patients (HCV-PSP) attending clinical practices in Romania and initiating glecaprevir/ pibrentasvir between 01 February 2022 and 11 July 2023. Patients ≥18 years of age with compensated liver disease F0-F4 fibrosis grade treatment-naïve or F0-F3 fibrosis grade treatment-experienced on previous interferon-based regimens from the HCV-PSP were included in the ODYSSEY study. Patients received glecaprevir/pibrentasvir for at least 8 weeks. Sustained virological response (SVR) was assessed at 12 weeks after the 8-week treatment (SVR12). Analyses were conducted on the core population (CP) and the CP with sufficient follow-up data (CPSFU). Results: The CP and CPSFU included 2,240 and 2,165 patients, respectively. In both populations, most patients were female (≥67.57%), aged >50 years (≥73.62%), and treatment-naïve (≥96.47%). F4 fibrosis was reported in 19% of patients. Hypertension was the most common relevant comorbidity, reported for 21% of patients; comorbidity rates increased with age. Overall SVR12 rates were 96.1% [95% confidence interval (CI): 95.2-96.8%) and 99.3% (95%CI: 98.9--99.6) in the CP and CPSFU, respectively. When stratified by gender, age category, comorbidities or fibrosis grade, SVR12 rates were >92% in the CP [except for the subgroups of patients with chronic kidney disease (87.5%) and depressive-/anxiety disorders (86.2%)] and ≥97.0% in the CPSFU. SVR12 rates were higher in female patients. In an exploratory analysis, in the CPSFU, the presence of diabetes mellitus [odds ratio (OR)=3.840; 95%CI: 1.093--13.495] and cardiovascular diseases (OR=7.904; 95%CI: 1.719-36.346) were associated with an increased probability to detect HCV RNA at 12 weeks post-treatment. Conclusions: The 8-week treatment with glecaprevir/pibrentasvir resulted in high SVR12 rates for multiple HCV-infected patient profiles encountered in real-life settings in Romania. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is characterized by flares of eczematous lesions accompanied by intense pruritus, which can tremendously impact quality of life (QoL). Despite continuous therapeutic progress, there are still unmet needs regarding AD management. Objective: This sub-analysis of the cross-sectional global study MEASURE-AD with 1558 AD patients treated with or eligible for systemic therapy aimed at characterizing the real-world burden of 98 patients in Austria and Switzerland. Patients were enrolled between October 2019 and June 2020. Assessing patient characteristics, treatment, disease severity, and patient-reported outcomes. Results: Mean age at time of diagnosis was 19.4 years with delayed diagnosis by an average of almost 3 years. All patients obtained treatment, 57.1% of them systemic therapy, mostly dupilumab. 45.9%–73.5% of all patients presented with moderate to severe disease and more than half of them suffered from moderate to severe pruritus, impaired QoL, and had experienced several flares. Furthermore, a negative impact on sleep, mental health, social life, and work productivity was revealed. Conclusions: This analysis confirms that AD is associated with a multidimensional burden despite treatment and demonstrates unmet needs regarding diagnostic delay, under-treatment with systemic therapy, and the development of efficacious therapies to improve clinical symptoms and QoL. [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). Objectives: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). Methods: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. Results: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. Conclusions: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice. [ABSTRACT FROM AUTHOR]

Brodalumab, a human monoclonal antibody that targets interleukin-17 receptor A (IL-17RA), is approved in the US and EU for treatment of adults with moderate-to-severe plaque psoriasis. Although brodalumab has demonstrated efficacy and safety vs placebo in clinical trials of patients with psoriasis and psoriatic arthritis (PsA), real-world evidence is needed to evaluate long-term effectiveness and safety of brodalumab in routine care. This interim analysis of the German Psoriasis Registry PsoBest examined patient profiles, treatment outcomes, and drug survival of first-time use of brodalumab for 12 months in adult patients with moderate-to-severe plaque-type psoriasis (with and without PsA) (data cutoff: June 30, 2021). Clinician and patient-reported outcomes of the total cohort (n = 227; PsA, n = 38) indicated a rapid response to brodalumab treatment within the first 3 months, which was maintained up to 12 months. The overall one-year drug survival rate was 76.2%, the mean time to discontinuation was 8.3 months. Reasons for discontinuation were mainly loss/lack of effectiveness, followed by adverse events, contraindication and skin clearance. In sum, brodalumab demonstrated rapid and sustained effectiveness and was well-tolerated over 12 months in German patients with moderate-to-severe psoriasis and PsA in a real-world setting. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the real-world safety profile of medical devices used in focal prostate cancer treatment utilizing the Manufacturer and User Facility Device Experience (MAUDE) database. Methods: The MAUDE database was searched for reports on high-intensity focused ultrasound (HIFU), cryoablation, laser ablation, and irreversible electroporation (IRE) devices used in prostate cancer treatment from 1993 to 2023. Adverse events were identified and categorized. Results: We identified 175 reports for HIFU, 1362 for cryoablation, 615 for laser ablation, and 135 for IRE devices, with 28, 284, 126, and 2 respective reports, directly related to prostate cancer treatment. The aggregated data revealed the majority of complications were minor, with 82.5% (n = 363 out of 440 total complications) classified as Clavien-Dindo grade 1 or 2. Common minor complications included erectile dysfunction and urinary retention. Severe complications such as rectal fistulas were noted in HIFU and IRE treatments, along with singular mortality due to pulmonary embolism in cryoablation. Conclusions: Our analyses from MAUDE reveal that devices used in focal therapy for prostate cancer are predominantly associated with minor complications, underscoring their overall real-world safety profile. However, the occurrence of severe adverse events emphasizes the critical importance of rigorous patient selection and meticulous procedural planning. These findings provide valuable insights into the safety profile of focal therapy devices and contribute to the growing body of evidence on their use in prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Background and Aims: There has been an evolving trend in the use of intermittently scanned continuous glucose monitoring (isCGM) among individuals with type 1 diabetes. Although isCGM is proven to be beneficial in the treatment of individuals with type 1 diabetes, its use leads to increasing device costs. This study aimed to investigate the long-term cost-effectiveness of isCGM. Methods: Long-term clinical outcomes and costs were projected using the IQVIA Core Diabetes Model (v10.0) based on the observed real-world outcomes of isCGM. The clinical input data for the analysis were sourced from a real-world patient cohort from Eastern Finland, including 877 adult individuals with type 1 diabetes with isCGM (i.e., Freestyle Libre 1 and 2). At the baseline, the patients' mean age was 48 years, and the mean duration of diabetes was 25.8 years. The mean baseline HbA1c was 8.6%, and the mean 12-month change from baseline in HbA1c was −0.37% after the initiation of isCGM. The cost-effectiveness analysis was performed over a lifetime time horizon. A discount rate of 3% was used for the future costs and health outcomes. Results: The projected use of isCGM was associated with improved quality-adjusted life year (QALY) expectancy of 0.84 QALYs after the start of isCGM. The direct lifetime costs were 7861 EUR higher with the use of isCGM, which resulted in an incremental cost-effectiveness ratio of 9396 EUR per QALY gained. Conclusions: According to the present analysis, the use of isCGM is considered cost-effective in adult individuals with type 1 diabetes in a real-world setting in Finland. [ABSTRACT FROM AUTHOR]

Objective: To evaluate quality of life, migraine disability, and work productivity and activity impairment in patients with migraine who received preventive treatment by comparing standard of care preventive medications and calcitonin gene-related monoclonal antibodies (CGRP mAbs), including galcanezumab alone. Methods: This cross-sectional study conducted across the United States (US) and Europe used data from the Adelphi Migraine Disease Specific Programme. Physicians completed record forms for consecutive patients, who then completed self-report forms assessing patient-reported outcomes (PROs) such as quality of life, migraine disability, and work productivity and activity impairment. T-tests, Fisher's exact test, and Mann–Whitney U test were used for analysis. Results: From May 2022 to June 2023, 557 physicians submitted data for 6723 patients. A total of 4036 patients (US 956; Europe 3080) with a history of preventive treatment were included (>60% female, >80% White, mean [standard deviation] age range, 38.7 [12.8] to 46.3 [12.1]). Patients who received 3+ lines of preventive therapy and were receiving CGRP mAbs (including galcanezumab alone) had enhanced health-related quality of life (HRQoL) compared to those who received standard of care. Similar findings were observed across Europe; however, in the US, there was no significant difference in any PROs. Conclusion: Patients with migraine in the overall population and Europe who received 3+ lines of preventive migraine therapy and were receiving CGRP mAbs/galcanezumab demonstrated enhanced HRQoL compared to those who received standard of care. PLAIN LANGUAGE SUMMARY: This study evaluated quality of life, migraine disability, and work productivity in patients with migraine who were treated with standard of care preventive medications or calcitonin gene-related monoclonal antibodies (CGRP mAbs), including galcanezumab alone. The study was conducted across the United States and Europe and included data from 557 physicians and 6723 patients. Results showed that patients with migraine who received 3+ lines of preventive therapy and were receiving CGRP mAbs in overall population and Europe demonstrated enhanced health-related quality of life (HRQoL) compared with those who received standard of care. However, in the US, there was no significant difference in HRQoL and migraine disability. The study concludes that CGRP mAb treatments, especially in patients requiring multiple lines of preventive therapy, are a viable approach for optimal migraine management. [ABSTRACT FROM AUTHOR]

Introduction: The 1-year PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational (PROFILE) study evaluated the real-world effectiveness and safety of sarilumab in patients with moderate-to-severe rheumatoid arthritis (RA). Methods: Safety endpoints included adverse events (AEs) and lab abnormalities. Effectiveness endpoints included the ACR core set. The primary endpoint was the change from baseline in Clinical Disease Activity Index (CDAI). All statistics are descriptive and p values were nominal. Results: In total, 595 patients were treated, of whom 223 (37.5%) received sarilumab monotherapy and 372 (62.5%) received combination therapy. Upon initiation of sarilumab, an improvement in the mean (SD) CDAI score was observed at week 24 [11.4 (10.3)] and was maintained through week 52 [10.0 (10.5)], resulting in a mean [SD] reduction of −14.9 (12.7) and −14.4 (12.9), respectively. There were consistent improvements in disease activity that were similar for patients on monotherapy vs. combination therapy. An increase in the proportion of patients achieving remission and low disease activity was reported. By week 52, both groups had improved physical function and quality of life. There were no new safety signals. The proportions of any patients reporting a treatment-emergent adverse event (TEAE) or serious treatment-emergent AE (SAE) was 66.2% and 5.9%, respectively, and were similar between both treatment groups. Overall, 15.6% of patients discontinued sarilumab treatment due to TEAEs. The most commonly reported TEAE of interest was neutropenia (14.1%). Conclusions: In this 1-year, observational real-world study, sarilumab therapy resulted in improved clinical outcomes. The safety profile was consistent with that observed in sarilumab randomized clinical trials. This study was entered on the German website (Paul Ehrlich Institute) on January 11, 2018, with NIS No.: 423. [ABSTRACT FROM AUTHOR]

In clinical trials, the percentage of patients discontinuing treatment with ocrelizumab due to adverse events was low. However, real-world populations are often more diverse than randomized controlled trials (RCTs), therefore it is important to assess discontinuation rates in real-world studies. This systematic literature review (SLR) was conducted to identify real-world discontinuation and persistence data for ocrelizumab in studies of patients with relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Searches were conducted in MEDLINE and Embase to identify relevant real-world studies that met pre-determined Population, Intervention, Comparison, Outcomes, and Study (PICOS) criteria. Only articles published in English were included, but the study country was not restricted. A total of 30 studies were included, with the majority reporting real-world persistence data that appear to be similar to or better than in the pivotal clinical trials, with only 1 study reporting higher discontinuation rates due to adverse events compared with the clinical trials. Other studies identified reported that the risk of discontinuation was higher for other disease-modifying therapies (DMTs) compared with ocrelizumab, and adherence was also higher for ocrelizumab versus other DMTs. These findings have clinical relevance, as other studies have reported improved clinical outcomes and lower care costs for patients that are persistent or adherent to other DMTs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the real‐world treatment patterns and outcomes for patients with pleural mesothelioma (PM) in the era of immunotherapy. Methods: This retrospective audit included patients with PM diagnosed within three tertiary referral centers in Queensland, Australia from January 2017 to July 2023. Patient and treatment characteristics and outcomes were recorded. Data was analyzed using descriptive statistics and the Kaplan‐Meier survival method. Results: A total of 90 patients were included: 84% were male, the median age was 75 years (range 70–79) and 85% had baseline Eastern Group Cooperative Group of 0–1. Subtypes included 54% epithelioid, 17% biphasic, 12% sarcomatoid, and 17% unspecified/unknown. First‐line treatment was received by 57/90 patients (63%) and 33/90 patients (37%) received the best supportive care (BSC). Chemotherapy was most used (63%) overall, but first‐line immunotherapy was more commonly used since ipilimumab/nivolumab was reimbursed by the Australian Pharmaceutical Benefits Scheme in July 2021. After first‐line treatment, only 40% received second‐line treatment and 60% received BSC. 12‐month overall survival (OS) and progression‐free survival for all patients were 53% (95% confidence interval [CI]: 43–65) and 25% (95% CI 15–40) respectively. 12‐month OS was 72%, 64%, and 29% for immunotherapy, chemotherapy, and BSC, respectively. There was no significant difference in survival between chemotherapy and immunotherapy (hazard ratio 1.28, 95% CI: 0.65–2.5, p = 0.5). Conclusion: In our unselected real‐world cohort, both chemotherapy and immunotherapy are active against PM, but the prognosis remains guarded. There remains a need for better treatment options, especially in the first‐line setting. Enrolment in clinical trials is crucial to improving outcomes in this debilitating disease. [ABSTRACT FROM AUTHOR]