Conditions Of Routine Clinical Practice Research Articles

Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value < 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

Abstract PO1-17-05: Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases

Abstract Background Breast cancer survivors are at risk for mortality from cardiovascular diseases (CVD). CVD and their treatments can impact breast cancer treatment selection and clinical outcomes. A cyclin dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) is more effective than ET alone for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) metastatic breast cancer (MBC). CDK4/6i plus ET is now the standard of care in the first-line setting for HR+/HER2 MBC. However, data on the effectiveness of CDK4/6i in MBC patients with CVD are limited. We compared overall survival (OS) and real-world progression-free survival (rwPFS) of palbociclib plus AI (PAL+AI) vs AI alone in HR+/HER2 MBC patients with CVD in routine US clinical practices. Methods The Flatiron Health longitudinal database contains electronic health records from >280 cancer clinics, representing >3 million actively treated cancer patients in the US. Using the Flatiron database, we conducted a retrospective analysis of 469 patients with HR+/HER2 MBC and CVD who started PAL+AI or AI as first-line therapy between February 2015 and March 2020. CVD prior to the initiation of PAL+AI or AI were identified based on their definitions within the National Cancer Institute-Comorbidity Index (NCI-CI), including myocardial infarction, congestive heart failure, peripheral vascular diseases, and cerebrovascular diseases. Patients were assessed from start of PAL+AI or AI to September 30, 2020 (data cutoff date), death, or last visit, whichever came first. OS was defined as months from start of PAL+AI or AI to death. rwPFS was defined as months from start of PAL+AI or AI to death or disease progression, evaluated based on clinical assessment or radiographic scan/tissue biopsy. Stabilized inverse probability treatment weighting (sIPTW) as primary analysis was used to balance baseline demographics and clinical characteristics. Cox proportional-hazards models were used to estimate the relative effectiveness of PAL+AI vs AI alone. Results Of the 469 eligible patients, 160 (34.1%) were treated with PAL+AI and 309 (65.9%) were treated with AI alone. Compared with AI-alone patients, those treated with PAL+AI were younger and were more likely to have de novo MBC, ≥2 metastatic sites, and lung/liver involvement. After sIPTW, patient characteristics were generally balanced. After sIPTW, median OS (95% confidence interval [CI]) was 40.7 months (30.956.0) in PAL+AI patients and 26.5 months (23.337.3) in AI patients (hazard ratio [HR]=0.732, 95% CI=0.5370.997, p=0.0476). Median rwPFS (95% CI) was 20.0 months (11.7–27.5) in PAL+AI patients and 12.5 months (9.718.3) in AI patients (HR=0.679, 95% CI=0.5120.900, p=0.0070). Consistent results were observed with multivariate Cox proportional-hazards models as sensitivity analysis. See Table for baseline patient characteristics and outcome results. Conclusions First-line PAL in combination with AI is associated with prolonged OS and rwPFS in patients with HR+/HER2 MBC and CVD in a real-world setting compared with AI alone. Further studies with larger cohorts and comprehensive assessments of comorbidities are needed to provide additional evidence of outcomes and safety of CDK4/6i plus AI for MBC patients with various comorbid conditions in routine clinical practice. Citation Format: Adam Brufsky, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Doris Makari, Rachel Layman, Hope Rugo. Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in metastatic breast cancer patients with cardiovascular diseases [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-05.

Effectivness and Safety of Orelabrutinib in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Retrospective, Real-World Study in China

Introduction: Orelabrutinib is a second-generation Bruton tyrosine kinase inhibitor (BTKi) with high kinase selectivity. Clinical studies have demonstrated that orelabrutinib achieved a high complete response rate of 26.3% in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), showing promising efficacy and acceptable safety profile. However, the real-world data of Orelabrutinib are not available. This study aimed to evaluate the effectiveness and safety of orelabrutinib-containing regimens for the treatment of patients (pts) with CLL/SLL in a real-world setting. Methods: This was a retrospective, multi-center, real-world study conducted. Pts (aged 18 years or older) with CLL/SLL who received at least 3 months of orelabrutinib-containing regimens between December 2020 and March 2023 were analyzed. Efficacy was evaluated by hematologic response rate (HRR), defined as the proportion of pts who met at least 1 of the following hematologic response criteria: hemoglobin response (pts having a recovery of hemoglobin value or ≥50% increase from baseline), platelet response (pts having a recovery of platelet count or ≥50% increase from baseline), or lymphocyte response (pts having a recovery of lymphocyte count or ≥50% reduction from baseline). Safety was assessed by adverse events (AEs) as per NCI-CTCAE 5.0. Results: 24 pts with CLL/SLL (12 males; 22 CLL) were included, with a median age of 62.5 years (range: 38-82). Most pts had an Eastern Cooperative Oncology Group score of 0-1 (17/24, 70.8%) and Rai stage III or IV disease (16/18, 88.9%). 7 pts with hypertension, of which 2 with very high-risk hypertension. 3 pts have previously received other BTKi. A total of 9 pts(37.5%) performed del(17p), TP53, or IGHV testing. Among them, pts received orelabrutinib 100 mg (2/24,) or 150 mg (22/24,) once daily. As of the cut-off date (July 13, 2023), the median follow-up was 10.67 (range, 2.73-25.77) months. 18 pts (16 CLL, 2 SLL) with abnormal hemoglobin value, platelet count, or lymphocyte count at baseline were evaluable for hematologic response. Hematologic response was achieved in 11 (61.1%) of 18 evaluable pts. Pts aged <65 years had a higher HRR versus pts aged ≥65 years (87.5% vs. 40.0%, p=0.040). HRR was 56.3% in CLL versus 100.0% in SLL pts, and 60.0% in pts with hypertension versus 61.5% without hypertension . Four of 11 responders had a hematologic response in at least two criteria (CLL, n=3; SLL, n=1), of which 3 pts had a hemoglobin response (Figure 1). The most commonly reported AEs included hemoglobin decreased (16.7%) and platelet count decreased (16.7%). Grade ≥3 AEs were white blood cell count decreased (4.2%), platelet count decreased (4.2%), and lymphocyte count decreased (4.2%). No pts experienced severe AEs. No cardiovascular AEs were reported during treatment in 7 pts with hypertension at baseline. Conclusions: This real-world study assessed the preliminary characteristics and clinical outcome of patients receiving orelabrutinib-containing regimens under routine clinical practice conditions in China. The orelabrutinib-containing regimens in this study furnished beneficial evidence for the treatment of CLL/SLL and is essential for determining the best treatment option, future data with a larger sample and longer follow-up will be updated.

Real-world utilization of guideline-directed genetic testing in inherited cardiovascular diseases.

Cardiovascular disease continues to be the leading cause of death globally. Clinical practice guidelines aimed at improving disease management and positively impacting major cardiac adverse events recommend genetic testing for inherited cardiovascular conditions such as dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), hereditary amyloidosis, and familial hypercholesterolemia (FH); however, little is known about how consistently practitioners order genetic testing for these conditions in routine clinical practice. This study aimed to assess the adoption of guideline-directed genetic testing for patients diagnosed with DCM, HCM, LQTS, hereditary amyloidosis, or FH. This retrospective cohort study captured real-world evidence of genetic testing from ICD-9-CM and ICD-10-CM codes, procedure codes, and structured text fields of de-identified patient records in the Veradigm Health Insights Ambulatory EHR Research Database linked with insurance claims data. Data analysis was conducted using an automated electronic health record analysis engine. Patient records in the Veradigm database were sourced from more than 250,000 clinicians serving over 170 million patients in outpatient primary care and specialty practice settings in the United States and linked insurance claims data from public and private insurance providers. The primary outcome measure was evidence of genetic testing within six months of condition diagnosis. Between January 1, 2017, and December 31, 2021, 224,641 patients were newly diagnosed with DCM, HCM, LQTS, hereditary amyloidosis, or FH and included in this study. Substantial genetic testing care gaps were identified. Only a small percentage of patients newly diagnosed with DCM (827/101,919; 0.8%), HCM (253/15,507; 1.6%), LQTS (650/56,539; 1.2%), hereditary amyloidosis (62/1,026; 6.0%), or FH (718/49,650; 1.5%) received genetic testing. Genetic testing is underutilized across multiple inherited cardiovascular conditions. This real-world data analysis provides insights into the delivery of genomic healthcare in the United States and suggests genetic testing guidelines are rarely followed in practice.

Expert design thinking workshops to analyze users’ perceived applicability of NUTRI-ONCOCARE algorithm to prevent and treat malnutrition in cancer patients under routine clinical practice conditions in Spain: the ALLIANCE study

PurposeNUTRI-ONCOCARE algorithm has been developed to identify and treat patients with solid tumors who are at risk of malnutrition. The present study is aimed at analyzing users’ opinion about this new tool and at assessing whether it is perceived as useful to achieve the behavioral change required for a successful integration of nutritional assessment into routine cancer care.MethodsDesign thinking Double Diamond process was applied. A multidisciplinary team composed of ten potential end-users (four oncologists, three endocrinologists, one nutritionist, and two hospital pharmacists) participated in three different workshops aiming to analyze the different tasks included within the NUTRI-ONCOCARE algorithm.ResultsUsers agreed on the need to perform nutritional assessment around cancer diagnosis and through the course of the disease using standardized tools included in hospital nutritional protocols and involving healthcare professionals with nutrition expertise. Nutritional evaluation and intervention should be individual and comprehensive, considering not only nutritional parameters but also patients’ functional status. According to participants’ opinion, the implementation of nutritional screening in routine clinical practice is limited by the lack of time and staff to conduct nutritional assessments, the low level of nutrition expert participation, and the poor support provided by hospital managers, which are often unaware of nutrition’s impact in cancer care.ConclusionsExperts recognized the importance of considering nutritional status in cancer patients and identified the opportunity provided by the NUTRI-ONCOCARE algorithm for this purpose, as it meets main requirements for being used routinely in clinical practice.

Real world data of a German Parkinson’s disease population: effectiveness and safety of safinamide in routine clinical practice

Background Parkinson’s Disease (PD) is a common progressive neurodegenerative disorder that leads to an imbalance of various neurotransmitters and affects cognitive, motor and non-motor function. Safinamide inhibits monoamine oxidase B in a highly selective and reversible manner and beyond that has anti-glutamatergic properties, with positive effects on motor and non-motor symptoms. The aim of the study was to obtain data about the effectiveness and tolerability of safinamide under routine clinical practice conditions in unselected patients with Parkinson’s disease (PD). Methods A post-hoc analysis of the German cohort of the European SYNAPSES study (a non-interventional cohort study). Patients were treated with safinamide as an add-on to levodopa and followed-up for 12 months. Analyses were done in the total cohort and in clinically relevant subgroups (patients older than 75 years; with relevant comorbidities; with psychiatric conditions). Results 181 PD patients were eligible for analysis. Motor symptoms included bradykinesia (76.8%), rigidity (77.3%), tremor (58.6%), and postural instability (27.1%). Non-motor symptoms were reported in 161 patients (89.0%), mainly psychiatric symptoms (43.1%), sleep disorders (35.9%), fatigue (30.9%), and pain (27.6%). 28.7% of patients were aged 75 years or older, 84.5% had relevant comorbidities, and 38.1% had psychiatric conditions. During treatment, the rate of motor complications decreased from 100.0% to 71.1%. UPDRS scores improved under safinamide, with a clinically important effect in 50% in the total score and 45% in the motor score. The positive effect on motor complications occurred already at the 4-month visit and was maintained over 12 months. At least one adverse event (AE)/adverse drug reaction (ADR) was reported by 62.4%/25.4% of patients, AEs were generally mild or moderate, and completely resolved. Only 5 (1.5%) AEs had a definite relationship to safinamide. Conclusions The benefit-risk profile of safinamide was favourable and consistent with the total cohort of the SYNAPSES study. In the subgroups, findings were congruent with the total population, which allows the clinical utilisation of safinamide also in more vulnerable patient groups.

Evaluation of the efficacy of an antioxidant combination for the modulation of metabolic, endocrine, and clinical parameters in patients with polycystic ovary syndrome

Objective To evaluate the efficacy of dietary supplementation with a combination of antioxidants (lipoic acid, N-acetylcysteine, vitamin B6, and S-adenosyl-L-methionine) for the modulation of metabolic, endocrine, and clinical parameters in comparison with oral contraception in non-diabetic women newly diagnosed with polycystic ovary syndrome (PCOS). Methods This was a prospective, partially randomized, multicenter study in which non-diabetic women with PCOS were recruited under routine clinical practice conditions and distributed in three groups to receive the following regimen for 6 months: 1) antioxidant combination (MN group); 2) oral contraception (OC group); or 3) oral contraception and the antioxidant combination (MN + OC group). General recommendation of healthy diet and regular exercise was given to all patients. Metabolic, endocrine, clinical, and quality of life parameters were recorded at baseline and after 6 months of therapy. Results A total of 96 women with PCOS were included in the study. After 6 months of treatment, the homeostasis model assessment-estimated insulin resistance (HOMA-IR) level was reduced only in the MN group, with a significant mean reduction of −0.92 points. Androstenedione was significantly reduced in all groups. Clinical parameters that significantly improved in all groups were hirsutism, acne, irregular menstruation, and quality of life, with no statistical differences between the groups. Conclusions This study showed that the antioxidant combination might be a suitable therapy for patients with PCOS when oral contraceptive is not indicated, because in all groups clinical parameters, irregular menstruation as well as androstenedione and quality of life were significantly improved with no statistical difference between groups.

HISTOPATHOLOGICAL STUDY OF NASAL MASSES, A RETROSPECTIVE STUDY IN A TERTIARY CARE CENTRE OF JHARKHAND

Background: Neoplastic and non-neoplastic lesions of the nasal cavity are common conditions in routine clinical practice among almost all age group of people. This study was carried out to rec Objective: ognize variety of benign and malignant nasal lesions with regard to age and sex in our region. A retrospecti Methods: ve study was done for a period of 1 year (January 2021 to December 2021). In this study, 50 patients are selected who presented in our hospital with nasal masses and having multiple clinical presentation.Result: Analysis of 50 cases of masses in nasal cavity, paranasal sinuses and nasopharynx was done. Nasal polyp was the most common non- neoplastic lesion. Among the neoplastic lesions, inverted papilloma was the most common benign lesion and squamous cell carcinoma was the most common malignant lesion. Nasal mases are m Conclusion: ore common in males. For proper evaluation of Sino nasal masses, clinical, radiological and histopathological evaluation should be done in all patients, but histopathology always gives a conrm diagnosis.

Disease control in patients with psoriatic arthritis in real clinical practice in Spain: MiDAS study

ObjectiveMiDAS study assessed the percentage of psoriatic arthritis (PsA) patients treated in routine clinical practice who achieved control of disease activity according to Disease Activity in Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA). MethodsObservational, non-interventional, cross-sectional, multicenter study conducted under conditions of routine clinical practice in 36 centers with outpatient rheumatology clinics in Spanish public hospitals. Patients included were adults (≥18 years) with ≥6 months PsA diagnosis according to classification for PsA (CASPAR) criteria and undergoing treatment ≥3 months. The main variable evaluated was the percentage of patients under remission and low disease activity, assessed through DAPSA and MDA. Results313 patients with PsA were included: 54.3% male; with mean age of 54.1±12.2 years and mean disease duration of 10.5±9.0 years. Mean C-reactive protein (CRP) serum levels were 4.9±7.3mg/L. At the study visit, 58.5% of patients were in monotherapy (17.6% biological and 40.9% non-biological) and 41.2% were receiving biological and non-biological therapy.59.4% of patients showed low disease activity (DAPSA≤14) and 19.8% were on remission (DAPSA≤4). Moreover, 51.4% of the patients reached an MDA status (≥5 MDA). ConclusionsAround 40% of PsA patients presented uncontrolled disease, highlighting the need to improve the management of these patients in clinical practice.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study

Introduction and objectivesUnderstanding the disease activity is fundamental to improve patient prognosis and patients’ quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. MethodsObservational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). Results313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). ConclusionsAlmost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Ultrasound in primary care: Consensus recommendations on its applications and training. Results of a 3-round Delphi study

Background The introduction of portable and pocket ultrasound scanners has potentiated the use of ultrasound in primary care, whose many applications have been studied, analyzed and collected in the literature. However, its use is heterogeneous in Europe and there is a lack of guidelines on the necessary training and skills. Objectives To identify the fundamental applications and indications of ultrasound for family physicians, the necessary knowledge and skills, and the definition of a framework of academic and pragmatic training for the development of these competencies. Methods A modified 3-round Delphi study was carried out in Catalonia, with the participation of 65 family physicians experts in ultrasound. The study was carried out over six months (from September 2020 to February 2021). The indications of ultrasound for family physicians were agreed (the > = 75th percentile was considered) and prioritised, as was the necessary training plan. Results The ultrasound applications in primary care were classified into seven main categories. For each application, the main indications (according to reason for consultation) in primary care were specified. A progressive training plan was developed, characterised by five levels of competence: A (principles of ultrasound and management of ultrasound scanners); B (basic normal ultrasound anatomy); C (advanced normal ultrasound anatomy); D (pathologic ultrasound, description of pathological images and diagnostic orientation); E (practical skills under conditions of routine clinical practice). Conclusion Training family physicians in ultrasound may consider seven main applications and indications. The proposed training plan establishes five different levels of competencies until skill in real clinical practice is achieved.

Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions.

Imatinib is the first therapeutic option for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Previous studies have shown an improvement in patient survival rates following the use of imatinib. Nevertheless, adequate plasma concentrations of imatinib are necessary to achieve such improvement in survival and limit the toxicity of the drug. This study aims to analyse the influence of imatinib plasma concentrations on efficacy and safety in the treatment of gastrointestinal stromal tumour. This descriptive, multicentre study analysed plasma levels of imatinib in patients diagnosed with gastrointestinal stromal tumour in the period 2019-2020. An optimal therapeutic range of 750-1500 ng/mL was established for the patient stratification based on their minimum plasma concentrations measured at the steady state. This study included 11 patients with metastatic disease in total, among whom only 54.5% (n = 6) had a minimum plasma concentrations measured at the steady state value within the therapeutic range. A median progression-free survival of 7.0 months was recorded for those patients with minimum plasma concentrations measured at the steady state < 750 ng/mL, while that median progression-free survival value remained unachieved for the group with minimum plasma concentrations measured at the steady state > 750 ng/mL (p = 0.005). The toxicity rate was 25% and 14.3% for patients with minimum plasma concentrations measured at the steady state > 1500 ng/mL and minimum plasma concentrations measured at the steady state ≤1500 ng/mL, respectively (p = 0.66). The present study aims to describe the correlation between the toxicity and effectiveness of imatinib as a function of minimum plasma concentrations measured at the steady state under routine clinical practice conditions. The results described here show the usefulness of imatinib plasma concentrations monitoring as part of the standard daily routine in our hospitals.

Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Approved CD123-Targeted Therapy Tagraxofusp: The First European Real-World Evidence Prospective Registry of First-Line Adult Patients

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells (pDC) that overexpress CD123, the interleukin-3 (IL-3) receptor alpha. Patients with BPDCN have a poor prognosis, with median overall survival (OS) of 8-14 months. Tagraxofusp (TAG; Elzonris®), a first-in-class CD123-targeted therapy comprising human IL-3 fused to a truncated diphtheria toxin payload, is currently the only approved first-line (1L) treatment for adult patients with BPDCN. TAG demonstrated clinically relevant efficacy as well as a manageable safety profile in the 0114 pivotal trial conducted in the United States (US), with an overall response rate of 75% and complete response (CR)/CRc (CR with residual skin abnormality not indicative of active disease) rate of 57% in 1L patients. Herein, we describe the first European (EU) real-world evidence prospective registry in patients with BPDCN who received TAG, with a focus on the effectiveness and safety of receiving TAG in a real-world setting. Enrolled patients will meet the updated diagnostic classification profile recently outlined by the World Health Organization (WHO) 2022 guidance. Currently, no published treatment outcomes data exist from prospective interventional clinical trials of 1L or relapsed/refractory (R/R) BPDCN outside the US. Data collected here will increase understanding of clinical outcomes in TAG-treated patients. The registry was designed to meet the requirements outlined in the marketing authorization of the EU Commission for further evaluation of safety and efficacy in patients with 1L or R/R BPDCN. Methods: This is a single-arm, postauthorization, noninterventional study (EudraCT: 2021-001684-24) in patients ≥18 years with a confirmed diagnosis of BPDCN (immunophenotypic analysis positive for CD123, CD4, and CD56, plus 1 additional pDC marker [TCF4, TCL1, CD303, or CD304], or a combination of 3 pDC markers, according to WHO 2022 classification). Patients will receive TAG under real-world routine clinical practice conditions: 12 mcg/kg/day intravenously (IV) on days 1-5 of a 21-day cycle (which corresponds to the approved dosage). The study will enroll a minimum 80 patients from 40-50 sites across EU, who are to be treated or who have recently (within 3 months) started treatment with TAG over an ~4-year period. Patients with R/R BPDCN will comprise an exploratory cohort. Primary objectives of the study are rates of CR after 3 months (± 1 month) of TAG and the incidence and severity of capillary leak syndrome (CLS). Secondary objectives are rates of patients bridged to stem cell transplant (SCT), OS, progression-free survival (PFS), best overall response (BOR), and duration of response (DOR). Secondary safety assessments are incidence and severity of adverse events of special interest: hepatic-, renal-, and cardiac-related events, and choroid plexitis events. TAG dose interruptions, number of TAG doses/cycles administered, and rates of IV albumin supplementation for diagnosed, or symptoms of, CLS will also be assessed. Data collection is anticipated quarterly, as well as at screening, enrollment, early discontinuation, and/or study end. A list of the assessments taken at each time point are shown in the Figure. Safety data collection will end 18 months after the last enrolled patient's first visit (LPFV). Interim analyses will be performed annually, with an effectiveness interim analysis scheduled for 12 months post-LPFV. Demographic, safety, and efficacy data will be summarized descriptively. The Kaplan-Meier method will be used to summarize PFS, OS, and DOR. The Clopper-Pearson exact method will determine the rates of patients bridged to SCT and BOR. Subgroup analyses for effectiveness and safety may also be performed on the basis of gender, age, or baseline Eastern Cooperative Oncology Group performance status. Enrollment is due to start in Q3-Q4 2022. Taking the registry as the basis, upon study finalization a complementary comparative analysis of effectiveness and safety from the TAG registry with a retrospective clinical cohort will be undertaken using appropriate methodology. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Metabolic control and treatment regimens in patients with type 1 diabetes in Castilla-La Mancha, 10 years later: The 2020 DIACAM1 study

ObjectiveTo evaluate degree of metabolic control and treatment regimens in patients with type 1 diabetes mellitus (T1DM) enrolled in the DIACAM1 study, after 10 years of follow-up under routine clinical practice conditions. Patients and methodsA total of 1,465 patients enrolled in the DIACAM1 study, a multicentre, cross-sectional study conducted in Castilla-La Mancha in 2010, were analysed. Of these patients, 58 (4%) died during the 10-year follow-up period. Anthropometric, clinical, laboratory and treatment data were reviewed for 1,121 (76.5%) patients in active follow-up. ResultsMean glycosylated haemoglobin (HbA1c) levels were 7.66% lower than in 2010 (p<0.001), 26% of patients achieved HbA1c levels <7%, 24.4% were obese, 51.7% had dyslipidaemia and 33.6% had hypertension. The following were found to be predictive factors for good glycaemic control (HbA1c<7%): good glycaemic control in 2010 (odds ratio [OR] 4.8); the use of intensified insulin regimens, including the Institute for Clinical Systems Improvement (ICSI) guideline and glucose monitoring (OR 2.8); no hyperlipidaemia (OR 1.97); and higher levels of education (OR 1.4). The recommended targets for lipid and blood pressure control were met by 76% of patients; 40% of the patients enrolled required drug treatment. ConclusionsGlycaemic control in patients with T1DM in Castilla-La Mancha improved after 10 years of follow-up. The use of intensified insulin regimens and technology applied to diabetes care appear to be determining factors in achieving this improvement. Despite the increase in the prevalence of cardiovascular risk factors, the majority of the patients achieved good lipid and blood pressure control.

P529: FIRST EUROPEAN REAL-WORLD EVIDENCE PROSPECTIVE REGISTRY OF FIRST-LINE ADULT PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM TREATED WITH FIRST-IN-CLASS CD123-TARGETED THERAPY TAGRAXOFUSP

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy derived from plasmacytoid dendritic cells that overexpress interleukin-3 (IL-3) receptor alpha (CD123). It is a highly aggressive disease characterized by skin and bone marrow involvement and is associated with a poor prognosis (median overall survival 8–14 months). Tagraxofusp (TAG, SL-401) is a first-in-class CD123-targeted therapy comprising human IL-3 fused to a truncated diphtheria toxin payload. It is currently the only approved first-line (1L) treatment for adult patients (pts) with BPDCN in Europe. As of July 2021, 65 pts with BPDCN have received TAG in a clinical setting outside the US as part of an expanded access program. Collecting real-world clinical data from TAG is important to increase understanding of clinical outcomes, especially in pts commonly underrepresented in clinical trials. We describe the first real-world evidence prospective registry in pts with BPDCN receiving TAG. It has been designed to meet requirements outlined in the marketing authorization of the European Commission for further evaluation of the efficacy and safety of TAG in pts with 1L or relapsed/refractory BPDCN. Aims: To investigate effectiveness and safety of TAG in pts with 1L BPDCN. Methods: This is a noninterventional, single-arm, post-authorization study (EudraCT: 2021-001684-24) in adult pts with BPDCN prescribed TAG under real-world routine clinical practice conditions (12 mcg/kg intravenously [IV] once daily on days 1–5 of a 21-day cycle, per the summary of product characteristics recommendation). A minimum of 80 pts will be included in approximately 40–55 sites in Europe, estimated over 4 years. Eligible pts have a diagnosis of BPDCN and are to be treated (or have recently started treatment) with TAG monotherapy as 1L treatment, per physician’s decision. Primary endpoints are rate of complete response (CR), defined as CR + clinical CR (CR with residual skin abnormality not indicative of active disease) after 3 months of treatment, and safety of TAG including the incidence and severity of capillary leak syndrome (CLS). Secondary endpoints include number of pts bridging to SCT, progression-free survival, overall survival, best overall response, duration of response, TAG dose interruptions/administration of IV albumin supplementation in pts with CLS or CLS symptoms, as well as safety and incidence and severity of adverse events of special interest (which include CLS and hepatic, renal, and cardiac events). Quarterly data collection is anticipated, as well as collection at screening, enrollment, early discontinuation, and study end (Figure). Safety data collection will end 18 months after the last enrolled pt’s first visit (LPFV). Interim analyses will be performed annually; an effectiveness interim analysis is scheduled at 20 months post-LPFV. Analyses will be performed using descriptive statistics. Survival data will be summarized using the Kaplan-Meier method. Subgroup analyses for effectiveness and safety may be performed, on the basis of gender, age, or baseline Eastern Cooperative Oncology Group performance status. Enrollment is planned to start by June 2022. Taking the registry as the basis, upon study finalization a complementary comparative analysis of effectiveness and safety data from the TAG registry with a retrospective clinical cohort will be undertaken using appropriate methodology, such as propensity score matching or inverse probability treatment weighting. Results: This is a TiP and there are no results at this time. Image:Summary/Conclusion: This is a TiP and there are no results at this time.

Long-term use of ospemifene in clinical practice for vulvo-vaginal atrophy: end results at 12 months of follow-up

Objective To assess the improvement in vulvovaginal atrophy (VVA) of postmenopausal women treated with oral ospemifene 60 mg/day under conditions of routine clinical practice after 12 months of follow-up. Methods The AYSEX study is a Spanish observational, prospective, and unicentric study in which five gynecologists recruited postmenopausal women with VVA in routine clinical practice treated with oral ospemifene 60 mg/day as an appropriate therapeutic option. Vaginal health, the most bothersome symptoms, sexual health, endometrial safety, bone resorption markers, bone densitometry, mammography, treatment satisfaction, and quality of life were assessed at baseline and after 12 months using appropriate scales. Results A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, a significant improvement was observed in all domains of Vaginal Health Index. This improvement was maintained at month 12 and only one patient remained with vaginal atrophy. In addition, a significant improvement was observed in the most bothersome symptoms, sexual function, and quality of life. There was no significant change in endometrial thickness, mammography, and bone health during the 12 months of treatment. Conclusions This study in routine clinical practice conditions confirms the results previously reported by randomized controlled trials, including a significant improvement in VVA, sexual function, quality of life, endometrial safety, and satisfaction with the treatment.

OP0042 LONG-TERM EFFICACY AND SAFETY OF CANAKINUMAB IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER (FMF) - INTERIM ANALYSIS OF THE RELIANCE REGISTRY

BackgroundFamilial Mediterranean Fever (FMF) is a chronic disease characterized by recurrent attacks of fever as well as serositis and bears the risk of serious complications (e. g. amyloidosis). Treatment of FMF according to EULAR aims to control acute attacks and subclinical inflammation as well as to improve patient´s quality of life1. Clinical data indicate that the inhibition of interleukin-1β with canakinumab (CAN) is effective in controlling and preventing flares in FMF patients2.ObjectivesThe present study explores the long-term efficacy and safety of canakinumab in routine clinical practice conditions in pediatric (age ≥2 years) and adult FMF patients.MethodsRELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Patients with clinically confirmed FMF diagnosis who routinely receive canakinumab are enrolled in order to evaluate effectiveness and safety of canakinumab. Disease activity and remission by physicians´ assessment, disease activity, fatigue and impact on social life by patients’ assessment, inflammatory markers and AIDAI (Auto-Inflammatory Diseases Activity Index) score were recorded at baseline and assessed at 6-monthly intervals within the 3-year observation period of the study.ResultsThis interim analysis of FMF patients (N=74) enrolled by December 2021 includes baseline as well as 6- to 24-month data. Mean age in this cohort was 25 years (2−61 years) and the proportion of female patients was 51 % (N=38). At baseline, median duration of prior CAN treatment was 1.0 years (0−6 years).At month 24, physician ratings report around 63% of patients in disease remission and patient-reported disease activity (mean PPA) decreased from moderate (3.0) to low (2.6) during the observation period. Other disease activity parameters also decreased (Table 1). A total of 18 serious adverse events were reported, of which 2 (1 case of tonsillectomy and 1 case of tachycardia) were classified as drug - related.Table 1.Baseline characteristics and 4th interim analysis data of patients with FMFBaseline12 months24 monthsNumber of patients, N744624Number (%) of patients with days absent from work/school during last 6 months6 (8)11 (24)9 (38)Number (%) of patients in disease remission (physician assessment)22 (45)23 (72)12 (63)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 10)2.0 (0; 7)2.0 (0; 10)Patient’s assessment of current fatigue; 0–10, median (min; max)5.0 (0; 10)2.0 (0; 10)4.0 (0; 10)Number (%) of patients without impairment of social life by the disease27 (50)28 (80)8 (67)CRP (mg/dl) | SAA (mg/dl) | ESR (mm/h); median0.2 | 0.7 | 8.00.2 | 0.5 | 4.00.2 | 0.7 | 6.0Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months24 monthsFever68 (93) | 14 (29)8 (25)3 (16)Abdominal pain67 (92) | 20 (41)10 (31)4 (21)Thoracic pain45 (62) | 5 (10)3 (9)1 (5)Headache34 (47) | 11 (22)7 (22)5 (26)Myalgia23 (32) | 6 (12)4 (13)2 (11)Arthralgia/arthritis39 (54) | 16 (33)9 (28)5 (26)Dermal symptoms (urticarial, maculopapulose)15 (21) | 5 (10)3 (9)0 (0)SAENumber of eventsIncidence rate# per 100 patient yearsAll types of SAE1814.03SADR21.56Incidence rate = number of events * 36,525 / sum of observation days (=46,848).CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse events.ConclusionInterim data of FMF patients from the RELIANCE study, the longest running real-life canakinumab registry confirm efficacy and safety of long-term canakinumab treatment.

Incidence, Risk Factors, and Outcomes of Rhegmatogenous Retinal Detachment after Intravitreal Injections of Anti-VEGF for Retinal Diseases: Data from the Fight Retinal Blindness! Registry

To report the estimated incidence, probability, risk factors, and 1-year outcomes of rhegmatogenous retinal detachment (RRD) in eyes receiving intravitreal injections (IVTs) of VEGF inhibitors for various retinal conditions in routine clinical practice. Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! Eyes of patients starting IVTs of VEGF inhibitors (ranibizumab, aflibercept, or bevacizumab) for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion from January 1, 2006, to December 31, 2020. All eyes that developed RRD within 90 days of IVTs were defined as cases with RRD and were matched with control eyes. Estimated incidence, probability, and hazard ratios (HRs) of RRD were measured using Poisson regression, Kaplan-Meier survival curve, and Cox proportional hazards models. Locally weighted scatterplot smoothing curves were used to compare visual acuity (VA) between cases and matched controls. Estimated incidence of RRD. We identified 16 915 eyes of 13 792 patients who collectively received 265 781 IVTs over 14 years. Thirty-six eyes were reported to develop RRD over the study period. The estimated incidence (95% confidence interval [CI]) per year per 1000 patients and per 10 000 injections was 0.77 (0.54-1.07) and 1.36 (0.95-1.89), respectively. The probability of RRD did not significantly increase at each successive injection (P= 0.95) with the time of follow-up. Older patients (HR [95% CI]= 1.81 [1.21-3.62] for every decade increase in age, P < 0.01) were at a higher risk of RRD, whereas patients with good presenting VA (HR [95% CI]= 0.85 [0.70-0.98] for every 10-letter increase in VA, P= 0.02) were at a lower risk. Neither the type of retinal disease (P= 0.52) nor the VEGF inhibitor (P= 0.09) was significantly associated with RRD risk. Cases with RRD lost 3 lines of vision on average compared with the prior RRD VA and had significantly fewer injections than matched controls over the year after the RRD. Rhegmatogenous retinal detachment is a rare complication of VEGF inhibitor IVT in routine clinical practice with poor visual outcomes at 1 year.

Role of ambulatory blood pressure on prediction of cardiovascular disease. A cohort study.

Ambulatory blood pressure (BP) is associated with mortality, but it is also interesting to expand its association with cardiovascular morbidity. This study sought to evaluate association with cardiovascular morbidity and cardiovascular mortality. Patients without cardiovascular disease who had a first 24-hour ambulatory BP monitoring were followed-up until the onset of the first event (a combined variable of cardiovascular mortality, coronary heart disease, cerebrovascular disease, peripheral arteriopathy, or hospital admission for heart failure). Changes in antihypertensive treatment couldn't be collected. Cox regression analysis was adjusted for risk factors and office BP. We included 3907 patients (mean age, 58.0, SD 13.8 years), of whom 85.5% were hypertensive. The follow up period was 6.6 (95% CI 5.0-8.5) years. A total of 496 (12.7%) events were recorded. The incidence rate was 19.3 (95% CI 17.7-21.1) cases per 1000 person-years. The patients with an event compared to the rest of patients were mostly men, older, with higher office and ambulatory systolic BP, higher prevalence of diabetes, chronic kidney disease, dyslipidemia, and non-dipper or riser circadian profile. In the fully adjusted model, office BP loses its significant association with the main variable. Ambulatory BP association remained significant with cardiovascular morbidity and mortality, HR 1.494 (1.326-1.685) and 0.767 (0.654-0.899) for 24-hour systolic and diastolic BP, respectively. Nighttime systolic BP also maintained this significant association, 1.270 (1.016-1.587). We conclude that nighttime systolic BP and 24-hour BP are significantly associated with cardiovascular events and cardiovascular mortality in patients without cardiovascular disease attended under conditions of routine clinical practice.