Real-world experience with glucagon-like peptide 2 analogues in patients with short bowel syndrome and chronic intestinal failure: results from an international survey in expert intestinal failure centers.

BACKGROUND AND AIMS: Glucagon-like peptide 2 (GLP-2) analogues are the first available disease-modifying treatments for patients with intestinal failure (IF) due to short bowel syndrome (SBS). Efficacy in terms of reduction of parenteral support (PS) has been demonstrated in multiple studies and real-world reports. However, it remains unclear how many patients are eligible to receive the treatment, when treatment is started after intestinal resection, how treatment efficacy is assessed outside of clinical trials, and how the treatment is modified in case of non-response or adverse events. The aim of this study was to investigate the real-world management of patients treated with GLP-2 analogues in expert centers around the world. METHODS: A survey questionnaire was developed by a multidisciplinary working group consisting of 52 questions related to various aspects of multidisciplinary care of SBS-IF patients. The 17 questions related to the use of GLP-2 analogues in clinical practice were analyzed for this study. The online survey was sent to 33 participating centers in a phase 3 study of a long-acting GLP-2 analogue. Only responses from countries with access to commercially available GLP-2 analogues were included in the study. A descriptive analysis was performed for each question. Results are presented as median (interquartile range). RESULTS: The responses from the 19 expert IF centers with access to GLP-2 analogues indicated that 10 (10-20) % of patients with SBS-IF were treated with a GLP-2 analogue, which was less than the number of eligible patients (30 (25-40) %). In most centers (10 centers, 53%), GLP-2 therapy was started 6-12 months after the last intestinal resection, with 5 centers (26%) starting later (12-24 months). Multiple parameters were used in combination to determine the response to GLP-2 analogues of which the three most common were >20% decrease in PS (95%), at least 1 day of PS reduction per week (84%) and increased urinary output (68%). In non-responders GLP-2 therapy was stopped within the first year by 67% of the centers. Finally, strategies in case of significant adverse events include stopping the GLP-2 analogue (used by 79% of experts), dose reduction (67%) and temporary treatment interruption (62%). CONCLUSION: The results of this survey completed by expert IF centers show the real-life use of GLP-2 analogues in clinical practice. Key learning points identified include the accounting for a period of intestinal adaptation before starting GLP-2 analogues and not stopping the treatment too early in case of non-response. The best strategy in case of adverse effects should be studied further.

Incorporating external controls in the design of randomized clinical trials: a case study in solid tumors.

BACKGROUND: The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible. METHODS: We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs. RESULTS: In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size. CONCLUSIONS: By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.

Freedom From Bleeds With Low-Dose Emicizumab Prophylaxis in Inhibitor-Positive Hemophilia A.

Background: The real-world data on outcome of hemophilia A patients with inhibitors (HAI) is sparse, especially from developing countries. In a setting of inequitable healthcare opportunities for hemophilia patients, especially those with inhibitors, low-dose practices of emicizumab are emerging. In the present article, we describe our experience of managing HAI patients on low-dose emicizumab over a period of 56 months (from December 2019 to August 2024). Methods: The present study reports the response of patients with inhibitor-positive severe hemophilia A (HAI) and a high annual bleed rate to two-dose schedules of emicizumab prophylaxis. All patients with HAI were previously managed with on-demand bypassing agents (BPAs) before being shifted to emicizumab. Seven patients were treated on standard dose of 3 mg/kg weekly for 4 weeks followed by once in 2 weeks, whereas 25 patients were started on low dose of 3 mg/kg once in 4 weeks with or without loading as per clinical decision. Bleed frequency, joint involvement, trough drug level and hemophilia joint health score (HJHS) were documented serially till in September 2023 (median of 16.4 months of follow-up). After September 2023, all patients were shifted to low dose of 3 mg/kg once in 4 weeks, following which 18 more patients were added, and this regimen has continued to date. Results: Thirty-two patients were initiated on emicizumab prophylaxis between December 2019 and December 2022. The median duration of follow-up of this cohort was 16.4 months (7.7 - 27.3 months). There was a significant reduction in bleed rate and improvement in HJHS in both arms after initiation of emicizumab. During a cumulative follow-up period of 562.8 months involving the 32 patients, only one patient experienced a bleed that required treatment. At 12 months post-initiation, the median baseline HJHS improved from 9 to 0 in children who received full dose and from 12 to 4 in those who received low dose. The mean emicizumab trough level observed in September 2023 in both groups were 29.92 ± 2.53 µg/mL and 12.6 ± 3.79 µg/mL, respectively. No significant difference was noted either in treated bleeds or HJHS score between patients who received standard or low-dose emicizumab. In view of clinical equivalence, the standard-dose patients were also shifted to low dose, and 18 more patients were subsequently added to this arm since September 2023. The last date of follow-up for this analysis was 31 Aug 2024. The cost of treatment on low-dose emicizumab in India compared to on-demand BPAs modeled on a child weighing 10 kg is analyzed. Conclusions: Emicizumab prophylaxis even in lower doses is effective in preventing bleeds and improving joint outcome in HAI with pre-existing high bleed rate and arthropathy. This opens up an avenue for providing equity in healthcare delivery for HAI in low- and middle-income countries (LMICs) such as India.

Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment.

Background: Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment. Objectives: To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM. Design: A multicentre, prospective, non-controlled, non-interventional, observational cohort study. Methods: Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected. Results: A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (p-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668). Conclusion: The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.

Long-term treatment results of pembrolizumab monotherapy: reconsideration of immune checkpoint inhibitor monotherapy.

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution. Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed. Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41-91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1-49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1-39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors. Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option.

Low to intermediate grade lung neuroendocrine tumours. A single centre real world experience.

INTRODUCTION: Lung neuroendocrine tumours (LNETs) are a rare heterogenous group of tumours whose incidence has been increasing. We investigated the diagnosis, treatment, and survival patterns of patients with low to intermediate grade LNETs. METHODS: A retrospective chart review of patients with low to intermediate grade LNETs, treated at a Canadian tertiary-level cancer centre was performed. RESULTS: We identified 59 patients. Most were G1or G2 and well or moderately differentiated. Forty-seven patients presented with local or locally advanced disease, of which 57.4 % received curative intent surgery. The rest were treated with definitive radiation, radical chemoradiation with platinum and etoposide, palliative chemotherapy with doxorubicin, or supportive care. The five-year overall survival (OS) for those treated surgically was 83 % versus 44 % in the non-surgical group. Metastatic disease was seen in 24/59 patients, with a five-year OS in patients with stage IV disease of 39 %. Of those with advanced or unresectable disease (n = 32), 21 received palliative systemic treatment with up to three lines of therapy. First-line treatment was most commonly chemotherapy with platinum/etoposide combination or somatostatin analogue therapy. Second-line treatment involved chemotherapy or targeted everolimus. PRRT was used once as a first-line and once as second-line therapy. Third-line included lanreotide or chemotherapy with capecitabine/temozolomide combination. CONCLUSION: Overall, patients with surgically resectable disease had a good five-year OS. However, inoperable or more advanced disease was associated with a poorer OS. Despite many treatment options, the sequence of treatments is poorly established. This highlights the need for further development and dissemination of evidence-based guidelines for LNET patients.

Use of transportability methods for real-world evidence generation: a review of current applications.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021-2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

Functional disability and disease activity are affected by social determinants of health in patients with rheumatoid arthritis.

BACKGROUND: The relationship between social determinants of health (SDH) and disease outcomes in rheumatoid arthritis (RA) is not well documented. METHODS: Data were extracted from the Ontario Best Practices Research Initiative (OBRI) registry for patients between January 2008 and April 2022. Adjusted mixed models analysis was used to investigate the effect of baseline SDH on disease activity (Clinical Disease Activity Index (CDAI)) and functional disability (Health Assessment Questionnaire-Disability Index (HAQ-DI)) 12 months after enrollment. The analyses were completed on multiple imputed data. RESULTS: There were 2651 patients with a mean age of 58.1 years (SD 12.9). The majority (77.8%) were female. Greater improvements in physical function were seen in patients who were full-time employed (difference = - 0.20; 95% CI - 0.28, - 0.11), part-time employed (difference = - 0.10; 95% CI - 0.19, - 0.02), or retired (difference = - 0.17; 95% CI - 0.25, - 0.08), compared to unemployed, those with highest income ($75,000 or more) (difference = - 0.23; 95% CI - 0.37, - 0.09). Caucasian was also associated with a positive impact on functional ability (difference = - 0.09; 95% CI - 0.17, - 0.02). In contrast, smokers had smaller improvements in physical function (difference = 0.07; 95% CI 0.002, 0.14). Interestingly, women had greater improvement in CDAI (difference = - 2.40; 95% CI - 3.29, - 1.51), while they reported less improving in their physical function (difference = 0.33; 95% CI 0.27-0.39). Achieving CDAI low disease activity/remission state was also more common in females. CONCLUSIONS: Our findings suggest that disease activity and functional disability are affected by different SDH factors. The effects of SDH should be better understood and addressed by rheumatologists to provide equitable healthcare for all patients with RA. Key points • This study explored a comprehensive panel of social determinants of health and their relationship to clinical outcomes. • Previously unreported factors such as employment status and income were found to influence clinical outcomes. • Our findings can help physicians to identify high-risk patients who may benefit from additional attention to their social background.

Management of vulnerable patients hospitalized for COVID-19 with remdesivir: a retrospective comparative effectiveness study of mortality in US hospitals.

BACKGROUND: COVID-19 remains a major public health concern, with continued resurgences of cases and substantial risk of mortality for hospitalized patients. Remdesivir has become standard-of-care for hospitalized COVID-19 patients. Given the continued evolution of the disease, clinical management relies on evidence from the current endemic period. METHODS: Using the PINC AI Healthcare database, effectiveness of remdesivir was evaluated among adults hospitalized with a primary diagnosis of COVID-19 between December 2021 and February 2024. Three cohorts were analysed: adults, elderly (≥65 years), and those with documented COVID-19 pneumonia. Analyses were stratified by oxygen requirements. Patients receiving remdesivir were matched to those not receiving remdesivir using propensity score matching. Cox proportional hazards models were used to examine in-hospital mortality. RESULTS: 169,965 adults hospitalized for COVID-19 were included, of which 94,129 (55.4%) initiated remdesivir in the first two days of hospitalization. Remdesivir was associated with a significantly lower mortality rate as compared to no remdesivir among patients with no supplemental oxygen charges (NSOc) (aHR [95% CI]: 14-day, 0.75 [0.69-0.82]; 28-day, 0.77 [0.72-0.83]) and among those with supplemental oxygen charges (SOc): 14-day, 0.76 [0.72-0.81]; 28-day, 0.79 [0.74-0.83]) (p<0.0001, for all). Similar findings were observed for elderly patients and those hospitalized with COVID-19 pneumonia. CONCLUSIONS: This evidence builds on learnings from randomized controlled trials from the pandemic era to inform clinical practices. Remdesivir was associated with significant reduction in mortality for hospitalized patients including the elderly and those with COVID-19 pneumonia.

Clinical efficacy and safety of new compound single tablet antiviral drugs in the treatment of HIV/AIDS.

AIMS: Genvoya, Biktarvy and Dovato are novel single-tablet antiretroviral therapy(ART). The aim of this study is to explore the therapeutic effects of these novel drugs on HIV/AIDS. MAIN METHODS: This retrospective cohort study, conducted at a single center, included a total of 200 HIV-treated patients who transitioned to these new antiretroviral drugs from July 2021 to August 2023. Data were extracted from electronic medical records at Ditan Hospital. The Genvoya group comprised 22 patients, and all subsequent switches in this group were to Biktarvy. The primary HAART group consisted of 178 patients initially treated with a first-line triple Highly Active Antiretroviral Therapy (HAART) regimen during the same period. This group was further subdivided into HAART+Dovato, HAART+Biktarvy, and HAART+Genvoya groups based on the switching regimen. The primary outcomes focused on changes in viral load and immune efficacy, while secondary safety indicators included blood/liver function, lipid parameters, renal function, blood glucose, blood uric acid, etc. KEY FINDINGS: The viral suppression rate was 100 % after the drug change treatment, and CD4+ T cell counts increased significantly across all four groups. Over the 6-month treatment period, there were increases in creatinine (Cr), low-density lipoprotein (LDL), high-density lipoprotein (HDL), erythrocyte count, and glomerular filtration rate (eGFR). Conversely, Alanine transaminase (ALT), Aspartate aminotransferase (AST), C-reactive protein (CRP), albumin (ALB), and blood glucose (Glu) levels decreased. SIGNIFICANCE: Genvoya, Biktarvy and Dovato are recommended for the treatment of HIV/AIDS and have a good safety profile.

Clinical outcomes for 2788 patients with transthyretin amyloidosis: Tafamidis meglumine early access program in France.

BACKGROUND: Early access experience in France with tafamidis meglumine, a selective transthyretin stabilizer for transthyretin-related amyloidosis cardiomyopathy (ATTR-CM), following transthyretin-related amyloidosis (ATTR) polyneuropathy approval and positive ATTR-ACT study results. AIM: To describe the characteristics and clinical outcomes for patients in the French ATTR-CM tafamidis meglumine early access programme (28 Nov 2018 to 01 Jun 2021). METHODS: Patients with confirmed ATTR-CM received tafamidis meglumine 20mg/day or 80mg/day. Demographic and clinical data were collected prospectively until patients discontinued treatment or died, or the programme ended. RESULTS: Overall, 222 physicians from 126 centres enrolled 2788 patients. The median age was 82years, 81.6% were male and New York Heart Association severity was class I for 12.8%, class II for 60.1% and class III for 27.0%. Overall, 1943 (74.6%) had genetic testing, and the results were available at tafamidis start for 1208 (62.2%) patients: 995 (82.4%) had wild-type ATTR and 213 (17.6%) had hereditary ATTR. Most patients started treatment≤12months after diagnosis (88.3%): 2268 (81.3%) at 20mg/day, with 401 (17.7%) increasing to 80mg/day. Median follow-up duration was 11.8months. New York Heart Association class improved or remained stable for 1299 (77.6%), whereas 376 (22.4%) worsened between inclusion and last follow-up. Among patients initiated at 80mg, 297 (81.1%) improved or remained stable and 69 (18.9%) worsened. New York Heart Association class progression did not vary with age. The 18-month survival rates were 89.8% (95% confidence interval: 87.0-92.0) among patients aged<80years, and 86.5% (95% confidence interval: 83.9-88.7) among those aged≥80years. CONCLUSIONS: Early tafamidis meglumine access was given to 2788 patients with ATTR-CM. New York Heart Association class progression and survival were consistent with previously published data.

Real-world treatment patterns and outcomes of patients with unresectable or metastatic urothelial carcinoma receiving systemic therapy in Japan.

BACKGROUND: Cisplatin-based chemotherapy has traditionally been the standard treatment for unresectable or metastatic urothelial carcinoma (mUC). Recently, the longstanding paradigm has changed with the emergence of immune checkpoint inhibitors and antibody-drug conjugates, such as pembrolizumab and enfortumab vedotin (EV). This longitudinal descriptive study aimed to identify real-world treatment patterns and assess the outcomes of patients with mUC between 2010 and 2023. METHODS: Patients with mUC who received first-line systemic therapy were identified from a Japanese electronic medical records database. A Sankey diagram was used to present the proportion of patients who transitioned to second- and third-line therapies. Kaplan-Meier survival analysis was used to estimate the time to next treatment (TTNT) and overall survival (OS). RESULTS: A total of 794 patients were included in this study. The median age of the patients was 73.0 years, and 72.9% were male. The most common primary tumor site was the bladder (59.7%). First-line therapy comprised cisplatin-based regimens in 52.0% of the patients (11.8% at standard doses, 32.4% at reduced doses, and 7.8% at unknown doses), carboplatin-based regimens in 32.1%, and other regimens in 15.9%. Among the patients enrolled after 2017, following the approval of pembrolizumab for mUC progressing after chemotherapy in Japan, 58.2% received pembrolizumab as second-line therapy, and 19.1% received EV monotherapy as third-line therapy. The median OS for the total population was 24.1 months, with patients enrolled between 2010 and 2016 having a shorter OS (21.1 months) than those enrolled between 2017 and 2022 (24.9 months). For patients with eGFRs of ≥60 and <60 mL/min/1.73 m2, the median OS was 24.1 and 23.8 months, respectively. CONCLUSION: Platinum-based regimens, including reduced-dose cisplatin and carboplatin, remain the predominant first-line systemic therapies. Since 2017, pembrolizumab and EV have become widespread choices for second-line and subsequent treatments, gradually surpassing the previously prevalent platinum-based regimens. The introduction of these novel therapies might have prolonged the OS of patients with mUC. A plain language summary is available in this article.

Real-world experience of emicizumab prophylaxis in Korean children with severe hemophilia A without inhibitors.

PURPOSE: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. METHODS: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. RESULTS: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0-21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. CONCLUSION: These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Attrition between lines of therapy and real-world outcomes of patients with HER2-positive metastatic breast cancer in Europe: a cohort study leveraging electronic medical records.

PURPOSE: To characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK). METHODS: This retrospective, observational, multi-country, cohort study collected electronic medical record data from women aged ≥ 18 years diagnosed with HER2 + mBC from 2017-2021. The primary endpoint was attrition rate (the proportion of patients receiving a line of therapy [LOT] with no further evidence of subsequent LOTs). Key additional endpoints included treatment patterns, real-world time to treatment discontinuation (TTD), and time to next treatment (TTNT). RESULTS: 29.6% (95% confidence interval [CI] 25.0-34.6) and 34.2% (95% CI 27.5-41.5) of treated patients with HER2 + mBC had no further evidence of treatment beyond 1L and second-line (2L) therapy, respectively. Attrition was primarily owing to death, move to end-of-life palliative care, loss to follow up, and "other" reasons. Treatment patterns were generally aligned with clinical guidelines. Decreases in TTD (12.1 months [95% CI 10.4-14.5] for 1L, 8.9 months [95% CI 7.3-11.9] for 2L, 6.4 months [95% CI 5.2-8.9] for 3L) and TTNT (15.4 months [95% CI 13.6-20.6] for 1L, 13.5 months [95% CI 10.8-19.4] for 2L) were observed with each subsequent LOT. CONCLUSION: Results unveil a large proportion of patients who do not benefit from state-of-the-art subsequent LOT, and suggest diminishing effectiveness with each subsequent LOT.

Avatrombopag for the treatment of patients with chemotherapy-induced thrombocytopenia: A case series.

Management of chemotherapy-induced thrombocytopenia (CIT) is challenging, often resulting in chemotherapy treatment delays, dose reduction, and treatment interruption. Randomized trials support the potential efficacy and safety of thrombopoietin receptor agonists in CIT management. A phase III trial of avatrombopag (AVA) demonstrated increased platelet counts (PC) in patients with solid tumours experiencing CIT. To complement those findings, this case series of six patients with solid tumours and CIT is presented. Results from these cases support the clinical benefit of AVA in improving PC and reducing the impact of CIT on tumour treatment, allowing continued therapy without dose reduction or treatment interruption.

Treatment of myasthenia gravis in france: A retrospective claims database study (STAMINA).

BACKGROUND: This study aimed to describe treatment patterns in patients with myasthenia gravis (MG) in France. METHODS: A retrospective cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2019. MG patients were identified using ICD-10 codes during hospitalization and/or long-term disease. We defined two adult subpopulations: a prevalent MG population of patients alive on 31/12/2019 and an incident population of newly identified patients with MG in 2012 and 2013. RESULTS: Among the 22,079 prevalent patients, 53.1% (n = 11,498) received at least one chronic MG treatment in 2019. Among these treated patients, 52.5% received Acetylcholinesterase inhibitors (AChEIs) only, 10.2% were treated with corticosteroids (CS) ± AChEIs, 7.3% with non-steroidal immunosuppressive treatments (NSIST) and CS, 24.2% with NSIST w/o CS, and 5.8% received immunoglobulin and/or plasma exchange. Among the 2,661 incident patients, 84.6% received at least one chronic MG treatment over the 6-year follow-up period, and among them, 79.0% had at least one treatment category change. During the first semester of follow-up, 28.1% of patients were treated with an immunomodulator (CS, NSIST). Among patients starting treatment with immunomodulator, the proportion of those treated with CS decreased from 35.3% at initiation to 10.9% at 6 years. CONCLUSION: This study illustrates the complexity of MG management. Significant CS sparing was observed over time. The frequent treatment changes especially in patients with an immunomodulator treatment reflect the high variability of the disease severity. The need for personalised treatment approaches in the management of MG to reduce the burden of disease remains.

Use of Hydrochlorothiazide in the United States Following Label Update About Skin Cancer Risk.

PURPOSE: On August 20, 2020, the United States (U.S.) Food and Drug Administration (FDA) issued a Drug Safety Communication (DSC) along with labeling updates to inform the public about a small increased risk of non-melanoma skin cancer (NMSC) associated with hydrochlorothiazide (HCTZ) use. This study aims to assess whether the DSC impacted HCTZ use in the U.S. METHODS: We conducted a trend analysis in the Sentinel Distributed Database using national healthcare administrative data from January 2017 to November 2022. We identified two cohorts each month: An overall cohort of all enrollees and a skin cancer cohort of those with a history of NMSC. For each cohort, we plotted the monthly proportion of patients receiving HCTZ-containing products among those receiving any thiazide diuretics. We performed interrupted time series analyses to quantify the impact of the DSC on these monthly proportions. Secondary analyses were conducted on the proportion of HCTZ users among patients receiving any antihypertensives. RESULTS: In the overall cohort, the DSC was only associated with a statistically significant but clinically negligible trend change of monthly HCTZ proportion within this cohort (0.018%; 95% CI, 0.012%-0.025%). Similar results were observed in the skin cancer cohort. The secondary analysis found no significant level change or trend change in the monthly proportion of HCTZ use among antihypertensive users. CONCLUSIONS: We did not observe significant changes in HCTZ use following the DSC about its NMSC risk, among the overall population and those with a history of NMSC. Our findings were in accordance with the DSC recommendation.

Gaucher disease in Brazil: a comprehensive 16 year retrospective study on survival, cost, and treatment insights.

Background: Gaucher's disease (GD), a lysosomal storage disorder, poses significant treatment challenges. This 23-year study assesses survival rates and treatment efficacy in Brazilian GD patients, integrating data from a 16-year cohort (2000-2015) and the TABNET/DATASUS medicines distribution data (1999-2022). Objective: To investigate the survival of GD patients in Brazil, identifying key risk factors and evaluating the impact of treatments funded by the Brazilian National Health System (SUS). Methodology: A 16-year retrospective cohort study was conducted using the National Database of SUS. Patients diagnosed with GD and treated with Enzyme Replacement Therapy (ERT) or Substrate Synthesis Inhibition (SSI) from 2000 to 2015 were included. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards model. The data from TABNET/DATASUS system from 1999 to 2022 was used to assess the trend in drug distribution beyond the main cohort. Results: The study included 1,234 patients. Survival rates at 5 and 10 years were 93.2% and 88.5%, respectively, with age and comorbidities like diabetes, cardiovascular diseases, and Parkinson's disease significantly affecting survival. Patients who received doses lower than DDD (n = 880) demonstrated a survival probability of 91.8%. In contrast, those with doses equal to the DDD (n = 15) showed a 100% survival probability, as no events were observed in this group. The greater than DDD group (n = 339) exhibited a survival probability of 81%. A log-rank test indicated a borderline statistical significance (p = 0.058) in the survival distributions among the different DDD adherence, with the lower dose group showing a favorable trend. Conclusion: This study provides insights into the survival rates and associated risk factors for GD patients in Brazil, contributing to the global understanding of GD and its management. While we acknowledge the inherent limitations of relying largely on electronic medical records and categorical codes, our findings underscore the need for early diagnosis, timely initiation of treatment, effective management of comorbidities, and personalized dosing strategies to improve patient outcomes. Future studies should aim to incorporate clinical verification of electronic data to further enhance the reliability and applicability of these findings.

Rates of febrile neutropenia and its causes in the real world.

Aim: Characterize febrile neutropenia in the real-world and explore potentially modifiable risk factors.Patients & methods: Characteristics of patient presenting with febrile neutropenia after systemic cancer treatment were investigated, with a thorough evaluation of potential risk factors.Results: The rate of febrile neutropenia requiring hospitalization was comparable with clinical trials (mean absolute difference 2%, 95% CI: -1-4%; p = 0.29). The in-hospital mortality rate was 6%. Most cases resulted from low-risk regimens (50%) and 18.2% presented no apparent risk factors. 42.4% of patients presented modifiable factors potentially involved in the occurrence of febrile neutropenia.Conclusion: Febrile neutropenia rate in contemporary real-world evidence is comparable with clinical trials. Appropriate G-CSF administration and avoidance of potentially harmful drug-interactions represent potential areas for improvement.

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Real-world Safety and Efficacy of Risankizumab in Psoriatic Patients: A Multicenter, Retrospective, and Not-interventional Study. / [[Artículo traducido]]Eficacia y seguridad del risankizumab en pacientes con psoriasis en el mundo real: un estudio retrospectivo, multicéntrico y no intervencionista.

BACKGROUND AND OBJECTIVE: risankizumab-a humanized monoclonal antibody that targets the p19 subunit of IL-23-has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. Objective To assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. METHODS: This was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. RESULTS: A total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7 ± 14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] > 30kg/m2). The mean baseline PASI score was 11.4 ± 7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤ 2 was greater in the group with a BMI ≤ 30 kg/m2 on weeks 4 (P = .04), 16 (P = .001), and 52 (P = .002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P = .001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P = .04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. CONCLUSIONS: Risankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.