Prospective Non-interventional Study Research Articles

Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (−28.9 ± 27.5 and − 34 ± 28.4) and control and powerlessness (−23.7 ± 28.2 and − 28.5 ± 26.2). Mean EAPP score change was −4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

Non-Interventional Prospective Observational Study of Platelet Rich Fibrin as a Therapy Adjunctive in Patients with Medication-Related Osteonecrosis of the Jaw

Background: Medication-related osteonecrosis (MRONJ) of the jaw is a severe and feared side effect of antiresorptive therapy in the oncological setting. With growing evidence that impaired angiogenesis may represent a key factor in pathogenesis, the aim of this study was to evaluate an autologous platelet concentrate as a possible additive in surgical therapy to optimize vascularization and, subsequently, resolution rates. Material and Methods: A non-interventional, prospective, multicenter study was conducted, and all patients with stage I-III MRONJ, undergoing antiresorptive therapy for an oncological indication, were included. The necrosis was treated surgically without (study arm A) or with (arm B) the addition of an autologous platelet concentrate (platelet-rich fibrin, PRF). Results: After 5, 14, and 42 days postoperative, wound healing (primary outcome: mucosal integrity) as well as downstaging, pain perception, and oral health-related quality of life (secondary outcome) were assessed via clinical evaluation. Among the 52 patients included, primarily with MRONJ stage I and II, the use of PRF as an additive in surgical therapy did not display a significant advantage for wound healing (p = 0.302), downstaging (p = 0.9), pain reduction (p = 0.169), or quality of life (p = 0.9). Summary: In conclusion, PRF as an adjunct did not significantly optimize wound healing. Further, no significant changes in terms of downstaging, pain sensation, and oral health-related quality of life were found.

Total cell-free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay.

Treatment for metastatic colorectal cancer (mCRC) is focused on prolonging survival and maintaining quality of life. It is important to establish prognostic and predictive markers to avoid extended, ineffective treatment. The aim of the present study was, by a novel approach, to analyze the association between cell-free (cf)DNA levels and outcome in patients receiving systemic therapy for incurable mCRC. The study was a prospective non-interventional biomarker study for patients receiving standard of systemic treatment for mCRC. Patients with mCRC, who, according to standard guidelines, were considered for treatment with EGFR inhibitors, were included. The cfDNA levels in consecutive plasma samples were measured by a direct fluorescence assay. The study included 47 patients. Blood samples were available at baseline (n=47); prior to the third treatment cycle (n=31); the first (n=33), second (n=22) and third response evaluation during treatment (n=17); and at progression (n=22). The disease control rate was 42 and 91% in patients with high (≥75th percentile of baseline cfDNA levels) and low cfDNA levels (<75th percentile of baseline cfDNA levels), respectively (P<0.001). Median progression-free survival (PFS) was 3.8 and 8.5 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.03, 95% CI 1.46-6.29, P<0.01). Median overall survival (OS) was 5.0 and 26.6 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.48, 95% CI 1.44-8.44, P<0.01). In the multivariate analysis, baseline cfDNA levels remained a significant predictor of PFS and OS. In conclusion, cfDNA is a promising prognostic tool in the personalized treatment of mCRC. cfDNA levels were estimated by a simple, rapid and inexpensive method (OPTIPAL II: ClinicalTrials.gov identifier no. NCT03750175; registered November 21, 2018).

ICU Resource Limitations During Peak Seasonal Influenza: Results of a 2018 National Feasibility Study.

Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. ICUs of 13 hospitals throughout the United States, 12 academic, and one community. ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018-April 2018). Responses were collected for 48 hours after each email query. The average weekly response among the sites was 79% (range, 65-100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

Use of potentially driver-impairing drugs among older drivers

BackgroundRoad safety is a major issue among seniors. Potentially Driver-Impairing (PDI) drugs are known to increase the risk of car accident. The aim of this cross-sectional study was to describe PDI-drug consumption among older drivers and determine associated factors.MethodsThe S.AGES cohort is a French non-interventional real-life prospective study of 3700 community-dwelling participants aged ≥65 years old, suffering from type 2 diabetes (T2DM), chronic pain or atrial fibrillation (AF). Baseline data of drivers with known treatment (n = 1783) were used for the analyses. PDI drugs were defined according to the French classification.ResultsOne thousand seven hundred eighty-three drivers were included (66% males; mean age 76 (Standard deviation = 5.78) years old). 21% (n = 373) took PDI drugs, 64% of which took only one (n = 239). The most frequent PDI drugs were: Zolpidem (11%; n = 60); Zopiclone (8%; n = 45); Bromazepam (8%; n = 44); Tramadol (7%; n = 39); Pregabalin (6%; n = 31). Drivers taking PDI drugs had more often chronic pain (OR [95% CI] = 2.30 [1.54–3.46]), history of depressive disorder (4.28 [3.00–6.14]) and polypharmacy (taking at least 5 different medications; 4.32 [2.97–6.41]), and less often T2DM (0.54 [0.37–0.79]), and AF (0.48 [0.32–0.71]). Conversely, they had a lower Activities of Daily Living score (0.34 [0.17–0.68]).ConclusionsThe rate of aged drivers in the S.AGES cohort taking PDI drugs is concerning and highlights the need to carefully assess and reassess PDI-drug prescriptions in this population, particularly hypnotics, anxiolytics and opioids.Trial registrationClinicalTrials.gov NCT01065909 (First posted: February 9th, 2010).

Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р &lt; 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р &lt; 0,001) and an increase in the mean scores of physical and mental functioning were noted (р &lt; 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p &lt; 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities.

«Натуральные» эстрогены в составе гормональных контрацептивов: влияние на сексуальную функцию, депрессию, качество жизни женщин

Study Objective: To evaluate the impact of combined oral contraceptives (COCs) containing 17β-estradiol/nomegestrol acetate and ethinylestradiol/drospirenone, on the sexual function, depression prevalence and severity, and quality of women’s life. Study Design: Randomised prospective non-interventional comparative parallel-group clinical study. Materials and Methods. The study included 90 women requiring contraception aged 18 to 45 years old (mean age: 29.9 (6.2) years old). Patients were randomised into two groups: group I (n = 45) took 1.5 mg of 17β-estradiol and 2.5 mg of nomegestrol acetate (E2/NОMAC); group II (n = 45) — 20 μg of ethinylestradiol and 3 mg of drospirenone (20EE/DRSP). Health Survey Short Form 36 (SF-36) of the Female Sexual Function Index (FSFI-6), Beck Depression Inventory initially and after 6 months of COC were used for questionnaire. Study Results. After 6 months of E2/NОMAC therapy, patients had better lubrication (from 4 [3; 4] to 5 [5; 5] [points, p &lt; 0.001) and higher female sexual function index (from 24 [22; 26] to 26 [24; 28] points, p = 0.01); reduced depression prevalence and intensity on Beck Inventory (from 7 [5, 11] to 6 [3, 7] points, p = 0.005); improved quality of life in the domain “physical functioning” (from 95 [80; 100] to 95 [95; 100] points, р = 0.03), and improved overall mental health component (from 34 [31; 38] to 38 [34; 41] points, р = 0.005). When 20EE/DRSP was used, there was no dynamics in FSFI-6 Questionnaire and Beck Inventory; however, patients demonstrated improved overall mental health component (from 43.7 [34; 51] to 48.6 [43; 52] points, р = 0.02) as well as improved physical (from 100 [95; 100] to 100 [100; 100] points, р = 0.03) and emotional functioning (from 100 [67; 100] to 100 [100; 100] points, р = 0.04). Conclusion. 6-month therapy with E2/NОMAC-containing COCs has positive effect on sexuality and promotes reduction in depression intensity, unlike COCs containing 20EE/DRSP which improve the quality of women’s life to a greater extent. Keywords: combined oral contraceptives, 17β-estradiol, nomegestrol acetate, ethinylestradiol, drospirenone, sexual function, depression, quality of life.

The effectiveness of combined topical product with fluocortolone pivalate and lidocaine for hemorrhoids: results of a multicenter observational study

AIM: to assess the changes in hemorrhoids symptoms and satisfaction with treatment against the background of treatment with a combined topical product Relief® Pro.PATIENTS AND METHODS:multicenter prospective non-interventional cohort study was done in 13 clinical centers in Russia. The study included patients aged 18 to 65 years with acute hemorrhoids of stages 1–2 treated with the combined product Relief® Pro (rectal suppositories, cream or a combination thereof). The follow-up period was up to 14 days (in the case of 2 visits to the clinical center after receiving the initial data). The analysis was performed on the basis of data obtained at Visit 2 (5–7 days of therapy) and Visit 3 (10–14 days of therapy) vs the initial data (Visit 1). Following criteria were used: the severity of hemorrhoid symptoms on the Sodergren scale, the severity of hemorrhoid symptoms (pain, bleeding, itching, edema, the presence of discharge, a feeling of discomfort), the size of the largest hemorrhoid node, the satisfaction of the doctor and the patient with treatment, assessment of the patient’s adherence to recommendations for lifestyle changes and treatment, evaluation of the use of the drug Relief® were evaluated as endpoints About the treatment process and patient preferences regarding the dosage form of the prescribed drug. In addition, adverse events were evaluated.RESULTS: the study included 1000 patients aged 18 to 65 years (men — 54.5%, women — 45.5%) Patients had grade 1 acute hemorrhoids (330 patients), grade 2 acute hemorrhoids (345 patients) and exacerbation of chronic hemorrhoids (325 patients). The drug Relief® Pro rectal cream was used by 333 patients; suppositories — 383 patients; joint therapy with both dosage forms — 284 patients. During follow-up (visits 2 and 3), positive dynamics was observed in patients — a decrease in the severity of hemorrhoid symptoms both during objective examination and according to patient questionnaires. So, according to the patients’ estimates, the use of Relief® Pro, regardless of the form, led to a decrease in the severity or disappearance of the main symptoms of hemorrhoids — bleeding, itching, edema, the presence of discharge, discomfort already by Visit 2 and in almost all patients by the end of observation. A similar change of the symptoms due the digital examination: by day 5–7, the severity of edema and bleeding in the perianal region, bleeding decreased. About 96% of patients and about 97% of doctors were satisfied with the treatment. Application of both forms of Relief® The ABM was characterized by good tolerability: there were no adverse events associated, according to the researcher, with the studied drug.CONCLUSIONS: combined topical product Relief® Pro is effective for hemorrhoids.

Evaluation of the Revogene® GBS DS assay performance for the intrapartum screening of group B streptococcus in comparison with intrapartum culture

Prevention of perinatal Group B Streptococcus (GBS) transmission is crucial in our effort to prevent Early-onset GBS disease. Here, we established the performance of the Revogene GBS DS assay for the detection of group B streptococcus on intrapartum vaginal samples in a laboratory environment using a prospective noninterventional study design. Intrapartum vaginal swabs were enriched using a selective culture method which served as study reference method. Overall, 119 patients were enrolled with an antenatal and intrapartum Group B Streptococcus colonization prevalence of 12.9% and 11.8%, respectively. Compared to intrapartum culture, the Revogene GBS DS assay had a sensitivity of 92.9% and a specificity of 99.1%, while the antenatal culture displayed a sensitivity 78.6% of and specificity of 96.2%. The Revogene GBS DS assay displayed an acceptable performance according to the European Group B Streptococcus consensus recommendations. Complementary studies in clinical practice are needed to confirm these findings.

Evaluation of bovhyaluronidase azoxymer efficacy in combined treatment of patients with endometriosis based on the results of multicenter prospective non-interventional study (ISLAND)

Background. Endometriosis is a chronic progressive recurrent disease associated with pelvis pain, menses disorders and infertility. The prevalence of endometriosis (EGE) tends to increase steadily and reaches 15% among women of reproductive age. Endometriosis-associated pain can persist despite surgical and drug treatment of this disease, resulting in a significant decrease in the quality of life of patients. The main causes of EGE-associated pain are local inflammatory, adhesive, neuro- and angiogenic processes. Currently, the search for alternative methods of pathogenesis-based therapy of the disease is one of the priority tasks. Given its anti-inflammatory, enzymatic, antioxidant effects and anti-adhesion mechanism of action, bovhyaluronidase azoximer, an enzyme agent with hyaluronidase activity, is a promising drug in the complex therapy of EGE.&#x0D; Aim. To compare bovhyaluronidase azoxymer efficacy in complex therapy of patients with EGE using dienogest (2 mg) versus monotherapy with this progestogen in real clinical practice.&#x0D; Materials and methods. 149 female patients of reproductive age were enrolled in the study after surgical treatment for EGE. The patients were divided into two groups: the first group (n=94) was treated with complex therapy by dienogest (2 mg) daily within 6 months in combination with suppositories containing bovhyaluronidase azoxymer (3000 IU): 1 suppositorium once within 3 days,10 administrations; and then 1 suppositorium once in 7 days, 17 administrations, within 120 days; the second group (n=55) received monotherapy with dienogest (2 mg) daily up to 6 months. EGE-associated pelvic pain intensity, uterine bleeding severity and life quality were assessed during the study, after 30, 90, 150 and 180 days with regard to the basic values.&#x0D; Results. There was a statistically significant reduction of pain intensity observed in both groups compared to the basic level, using visual analogue scale of pain (VAS), the Biberoglu and Berman scale, but there was a distinct trend towards a more significant decrease in pelvic pain score basing on VAS in patients received complex therapy versus monotherapy with dienogest 2 mg after 30 days of treatment (p=0.051). Life quality assessment of patients in both groups revealed statistically significant increase in scores for all values of the SF-36 life quality scale just after the second follow-up visit. More significant life quality improvement in patients was observed with complex therapy with regard to such descriptors of the SF-36 Questionnaire as Physical functioning, Role-physical functioning, Pain intensity (p0.05).&#x0D; Conclusion. Bovhyaluronidase azoxymer in combination with dienogest (2 mg) improves the overall therapy effectiveness for EGE and is associated with more significant reduction in pelvic pain intensity, inflammatory and adhesive processes in the pelvis, and significant life quality improvement compared to monotherapy with 2 mg dienogest.

Ensuring hemodialysis adequacy by dialysis dose monitoring with UV spectroscopy analysis of spent dialyzate.

Introduction:Patients’ session-to-session variation has been shown to influence outcomes, making critical the monitoring of dialysis dose in each session. The aim of this study was to detect the intra-patient variability of blood single pool Kt/V as measured from pre-post dialysis blood urea and from the online tool Adimea®, which measures the ultraviolet absorbance of spent dialyzate.Methods:This open, one-armed, prospective non-interventional study, evaluates patients on bicarbonate hemodialysis or/and on hemodiafiltration. Dialysis was performed with B. Braun Dialog+ machines equipped with Adimea®. In the course of the prospective observation, online monitoring with Adimea® in each session was established without the target warning function being activated. A sample size of 97 patients was estimated.Results:A total of 120 patients were enrolled in six centers in China (mean age 51.5 ± 12.2 years, 86.7% males, 24.2% diabetics). All had an AV-fistula. The proportion of patients with blood Kt/V < 1.20 at baseline was 48.3%. During follow-up with Adimea®, the subgroup with Kt/V > 1.20 at baseline remains at the same adequacy level for more than 90% of the patients. Those with a Kt/V < 1.20 at baseline, showed a significant increase of Kt/V to 60% of the patients reaching the adequacy level >1.20. The coefficient of variation for spKt/V as evaluated by Adimea® was 9.6 ± 3.4%, not significantly different from the 9.6 ± 8.6% as blood Kt/V taken at the same time.Conclusion:Online monitoring of dialysis dose by Adimea® improves and maintains dialysis adequacy. Implementing online monitoring by Adimea into daily practice moves the quality of dialysis patient care a significant step forward.

Antiangiogenic therapy in pretreated patients with lung adenocarcinoma without activating mutations: new features

The possibilities of treatment of patients with metastatic non-small cell lung cancer have significantly expanded in the recent years. Several combined regimens of chemoimmunotherapy are currently being proposed as the first line, some patients with PD-L1 overexpression may be prescribed pembrolizumab or atezolizumab in monotherapy. Standard platinum-containing chemotherapy (PCT) has lost its position and is relevant only for contraindications to immuno-oncological (IO) drugs. The change in the standart of the first line inevitably led to the search for new optimal modes of the second line. The strategy of "angio-immunogenic switching" is promising after progression on the regimens with IO, anti-angiogenic drugs are used. Nintedanib a multikinase angiogenesis inhibitor in combination with docetaxel is a standard second-line therapy option in patients with lung adenocarcinoma after progression on PCT. The effectiveness of this regimen is being studied in a prospective non-interventional VARGADO study. The patients were divided into 3 cohorts, depending on which regimen was used earlier one line of PCT or PCT, followed by IO or chemoimmunotherapy. The results showed that the combination of docetaxel + nintedanib was effective both as a third line (after PCT and IO), and in the second after chemoimmunotherapy. The research is ongoing.

Pomalidomide plus dexamethasone for patients with relapsed or refractory multiple myeloma: Final results of the non-interventional study POSEIDON and comparison with the pivotal phase 3 clinical trials.

BackgroundPrognosis of patients with multiple myeloma (MM) who have relapsed on or become refractory to immunomodulators and bortezomib is poor, and treatment options are limited. While pomalidomide plus low‐dose dexamethasone (POM/DEX) has demonstrated efficacy in clinical trials, real‐world evidence is scarce.Patients and MethodsPOSEIDON was a prospective non‐interventional study designed to evaluate effectiveness, safety and quality of life (QoL) of POM/DEX in patients with relapsed or refractory MM (R/RMM) pretreated with at least two prior therapy lines including both lenalidomide and bortezomib in real world in Germany. Patients received POM/DEX according to physicians’ choice. Data were analyzed descriptively.ResultsBetween 2014 and 2017, 151 patients were enrolled, 144 patients with a median of three prior therapy lines qualified for effectiveness analysis. Median age was 73.2 years. Median progression‐free and overall survival were 6.3 months [95% confidence interval (CI) 5.2, 8.6] and 12.9 months [95% CI 10.6, 15.1]. Most frequent grade 3/4 adverse events were leukopenia (8.2%), pneumonia (7.5%) and anemia (5.5%). QoL was maintained after start of POM/DEX.ConclusionThe results of POSEIDON support the effectiveness and safety of POM/DEX in R/RMM patients pretreated with lenalidomide and bortezomib and highlight the clinical value of the POM/DEX regimen in the real‐world setting.Registered at clinicaltrials.gov (NCT02075996).

Real-World Efficacy and Safety Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Real-World Efficacy and Safety Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Real-World Outcomes for Pediatric and Young Adult Patients with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL) Treated with Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Real-World Outcomes for Pediatric and Young Adult Patients with Relapsed or Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (ALL) Treated with Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Safety and Effectiveness of Venetoclax/Rituximab in Bcri-Naïve and Bcri-Exposed Patients with Relapsed/Refractory CLL Under Real-Life Conditions - Data from the Observational Verve Study

BackgroundIn clinical trials, venetoclax has shown high efficacy and good tolerability in patients with chronic lymphocytic leukemia (CLL). Retrospective cohort studies have examined outcomes with venetoclax in B-cell receptor pathway inhibitor (BCRi) naïve and exposed patients with relapsed/refractory (R/R) CLL in the real world setting. However, prospective real-world data on the sequencing of new agents in the R/R setting are limited. The prospective non-interventional observational study VeRVe is assessing effectiveness, safety, and quality of life in CLL patients treated with venetoclax in Austria, Germany, and Switzerland according to local label. Here we report outcomes in patients treated with venetoclax in combination with rituximab (VenR) in BCRi-naïve and BCRi-exposed patients.MethodsAdult patients with CLL requiring therapy treated with VenR according to local label were included in this analysis. Patient visits are scheduled at the physician's discretion and according to clinical practice. Study documentation is possible at baseline, weekly during ramp-up, monthly until the end of 6 months and 3-monthly afterwards up to a maximum of 3 years. Response assessment according to iwCLL criteria can be documented at the end of ramp-up, after 3, 12, and 24 months. Analyses were performed for subgroups of BCRi-naïve and BCRi-exposed patients.ResultsUntil April 26, 2021, 94 patients treated with VenR had been enrolled in the ongoing study and had received at least one dose of venetoclax (safety population). For 72 patients, treatment response had been documented at least once (effectiveness population). Enrolled patients had a median of 1 (range 1-10) previous lines of therapy. 57 patients (61%) had previously been treated with chemoimmunotherapy (CIT) and were BCRi-naïve, 32 patients (34%) had received at least one prior BCRi and 7 (7%) had received other prior treatment options. BCRi-naïve patients had a median of 1 prior therapies (range 1-4), while BCRi-exposed patients had received a median of 3 prior therapies (range 1-10). Risk factors were more common in the BCRi-exposed group (38% of patients had a documented del(17p), 34% a TP53 mutation, and 41% an unmutated IGHV status) in comparison to the BCRi-naïve group (14% del(17p), 16% TP53 mutation and 40% unmutated IGHV). Median age at baseline was 72 and 71 years for BCRi-naïve and BCRi-exposed patients, respectively. 65% vs. 84% of BCRi-naive and BCRi-exposed patients had at least one comorbidity.In the BCRi-exposed group, 29 patients (91%) had a BCRi as last prior therapy before VenR initiation with a median duration of prior BCRi therapy of 18 months (range 1 - 61 month). Most frequent reasons for discontinuation of prior BCRi therapy were AE/SAE (11 patients) and disease progression (12 patients).The reported best overall response at 12 months after VenR initiation was 83% (CR+CRi 55%; PR: 28%) for BCRi-naïve and 85% (CR+CRi 30%; PR: 55%) for BCRi-exposed patients (figure 1). After a median follow-up of 315 days the estimated 12-months OS and PFS rate were both 94.8% for BCRi-naïve patients, whereas the estimated 12 months OS and PFS rate for BCRi-exposed patients were 79.1% and 75.7%, respectively, with a median follow-up of 371 days. 79% / 25% of BCRi-naïve and 90% / 44% of BCRi-exposed patients had AEs / SAEs. No new safety signals were observed.ConclusionIn this analysis of real-world use of venetoclax in R/R CLL, patients receiving venetoclax in combination with rituximab were predominantly BCRi-naïve. BCRi-exposed patients were more heavily pre-treated, exhibited more genetic high-risk factors, and a higher proportion of patients with comorbidities. Yet, these patients achieved comparable overall response rates. However, complete remissions were more common and the 12 months OS and PFS rates were higher in BCRi-naïve patients. In both groups, VenR treatment was well tolerated. VenR represents a suitable treatment option in BCRi-naïve as well as BCRi-exposed patients. [Display omitted] DisclosuresRossi: Gilead: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Verastem: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Cellestia: Honoraria, Research Funding. Hebart: AstraZeneca: Honoraria; Janssen: Honoraria; BMS: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Losem: AbbVie: Honoraria; Amgen: Honoraria. Wolff: Bayer: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Teva: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Schmidt: AbbVie: Current Employment. Famulla: AbbVie: Current Employment. Schmidt: Takeda: Honoraria; Biotest: Honoraria; Alexion: Honoraria; Sanofi-Aventis: Honoraria; Novartis: Honoraria; Incyte: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Noesslinger: Jansen: Honoraria; Roche: Honoraria; Celgene: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria. Schwaner: AbbVie: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Servier: Honoraria.

Implementation of Escort-HU Extension: European Sickle Cell Disease Cohort - Hydroxyurea - Extension Study : Interests and Methodology

The efficacy and long-term effectiveness of hydroxycarbamide/hydroxyurea (HU) in the prevention of painful crises and in the decrease of mortality and morbidity in sickle cell disease (SCD) patients have been established (Charache et al. 1992; Steinberg et al 2010, Voskaridou et al 2010).From January 2009 to March 2019, the non-interventional prospective cohort study ESCORT-HU was conducted to evaluate the use of HU in real-life conditions and to collect information on the long-term safety of HU when used in current practice for the prevention or treatment of symptomatic complications in patients with sickle cell disease (SCD) (Montalembert et al 2021). A total of 1906 patients, 55% of adults, were enrolled in this study in 62 centres (Germany, Greece, Italy and France). The mean exposure to HU in this cohort was 30 months, for a cumulative exposure of 7310 patient-per year. The main objectives of ESCORT-HU have been fulfilled as regards the collection of data on the most common concerns associated with the use of HU in SCD patients: myelosuppression, child growth, concomitant administration of live vaccines, safety in population with renal and hepatic impairment and frequency of SCD events (painful crises, acute chest syndrome, stroke, acute splenic sequestration, infections, blood transfusions and hospitalizations) (Montalembert et al 2021).In order to better identify potential long-term risks and specific concerns of HU therapy, ESCORT-HU extension is being implemented in Europe with the goal of 2500 patients enrolled. Main risks targeted by the study are leg ulcers, one of the most limiting factors to continue a treatment with HU. Patients will be recruited over a 5-year period. In addition to patients already involved in the first ESCORT-HU study, new at-risk patients might be added such as •patients with a history of HU exposure of at least 5 years, to allow a follow-up of patients treated with long-term HU to fully estimate the incidence of potential risk of malignancies•prepubescent children aged more than 10 years for girls and more than 13 years for boys in order to document impact or not of HU on puberty and realisation of cryopreservation,•patients with a history of leg ulcers, to search for discriminating criteria between leg ulcer caused by the disease and HU-induced leg ulcer,•pregnant women without interruption of HU 3 months before the beginning of the pregnancy and males treated with HU whose partner is pregnant and without discontinuation of HU 3 months before the beginning of the pregnancy. To date, there is a limited number of pregnancies exposed to HU with documented outcome. Despite no adverse effects on pregnancy or on the health of the foetus/new-born have been registered, an increase of the number of pregnancies with documented outcomes will allow for meaningful assessment of foetal outcome following exposure to HU during pregnancy,10 months after the beginning of ESCORT-HU extension, 818 patients have been enrolled in 70 investigational sites in 4 countries (Greece, Italy, Germany and France) (see Graph below). A first steering committee was hold in June 2021. Its conclusions were that distribution of patients (genotype, sex, age) was consistent with the first study and the number of events reported until now was coherent with what was expected per year, with no occurrence of major concern.This extension study involves most of competence centres which manage SCD patients. SC patients have become increasingly well cared for in recent decades and have seen their life expectancy increase. HU treatment is now a chronic treatment possibly for life in many patients with SCD, better its knowledge of its efficiency and tolerance, better patient adherence to treatment will be. [Display omitted] Disclosuresde Montalembert: Addmedica: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy. Voskaridou: ADDMEDICA: Consultancy, Research Funding; BMS: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; NOVARTIS: Research Funding; PROTAGONIST: Research Funding; IMARA: Research Funding. Oevermann: NOVARTIS: Consultancy; GBT: Consultancy. Joseph: bluebird bio: Consultancy. Colombatti: BlueBirdBio: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding; Fabre Foundation: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy; Emmaus: Consultancy; Hemanext: Consultancy. Brousse: BLUEBIRDBIO: Consultancy; ADDMEDICA: Consultancy. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees.

Efficacy and safety of azilsartan medoxomil in various doses in patients with metabolic disorders

Background. Obesity is an independent risk factor of the cardiovascular complications in patients with arterial hypertension (HTN). It can directly contribute to an increase in blood pressure (BP). Thus, the treatment of patients with HTN and obesity becomes a complex clinical problem, which requires new highly effective antihypertensive drugs.&#x0D; Aim. To assess the effectiveness and safety of novel angiotensin II receptor blocker azilsartan medoxomil (AZL-M) as monotherapy and in free combinations with diuretics and/or calcium antagonists in obese or overweight patients with HTN in real clinical practice.&#x0D; Materials and methods. An international multicenter observational non-interventional prospective study of the efficacy and safety of AZL-M in patients with hypertension and overweight or obesity was performed in the Russian Federation and the Republic of Kazakhstan. Patients took the drug for 6 months in accordance with the approved local instructions for use. All examinations were performed in accordance with routine clinical practice on the basis of a physicians decision.&#x0D; Results. In patients prescribed AZL-M as monotherapy (without dosage changes during the study) a significant decrease in systolic and diastolic blood pressure (systolic BP and diastolic BP, respectively) was observed (p0.001, compared to baseline); the average decrease in systolic BP and diastolic BP was 30.5012.67 and 14.478.65 mmHg, respectively (n=865). Target BP (140/90 mmHg or 140/85 mmHg in patients with diabetes mellitus) was achieved in 112 (94.12%), 547 (92.24%) and 135 (88.24%) of patients who were prescribed AZL-M at doses of 20, 40, or 80 mg/day, correspondingly. In patients receiving AZL-M in combination with a diuretic or calcium antagonist, the rate of achievement of ad blood pressure targets was 78.887.5% and 81.385.5%, respectively, and the frequency of response to therapy was 68.892.9% and 81.393.9%, respectively. During the entire observation period, 43 adverse events (AEs) were recorded, the most common of which were arterial hypotension (14 cases). All AEs associated with the study drug were of mild or moderate intensity.&#x0D; Conclusion. AEs administered as monotherapy and as part of combination therapy provided a statistically and clinically significant decrease in BP and a high frequency of target BP achievement in patients with HTN and metabolic disorders associated with overweight or obesity. Given the high efficacy and good tolerance of the drug, AEs can be considered as the drug of choice for the treatment of HTN in patients with overweight or obesity.

Determination of the accuracy of osteoporotic fractures risk assessment in patients with rheumatoid arthritis using the prognostic model, developed at V.A. Nasonova Research Institute of Rheumatology, and the FRAX algorithm

Objective: comparison of the accuracy of risk assessment of low-energy fractures in patients with rheumatoid arthritis (RA) using the prognostic model developed at V.A. Nasonova Research Institute of Rheumatology, and the Russian model of the FRAX algorithm.Patients and methods. A prospective long-term observational non-interventional study included 70 women aged 40–80 years with a definite diagnosis of RA (ACR, 1987). All patients underwent dual-energy X-ray absorptiometry at baseline and over time; clinical and anamnestic data were analyzed, including information on fractures that occurred during the observation period, confirmed by medical documents.Results and discussion. The sensitivity and specificity of the FRAX algorithm were 67 and 56%, the sensitivity and specificity of the prognostic model of V.A. Nasonova Research Institute of Rheumatology – 78 and 56%, respectively. The diagnostic accuracy of the FRAX algorithm and the predictive model was 58 and 61%, respectively.Conclusion. The predictive model developed at V.A. Nasonova Research Institute of Rheumatology, showed higher diagnostic accuracy and sensitivity, as well as comparable specificity with the FRAX algorithm in assessing fractures in RA patients.

Effectiveness of early abobotulinum toxin (Dysport&lt;sup&gt;®&lt;/sup&gt;) injections in patients with upper limb spastic paresis after traumatic brain injury in real clinical practice: results of a multicenter observational non-interventional prospective study (Adults with post Traumatic Brain Injury (TBI) upper limb (UL) spasticity – APTULS)

The article reveals results of the first russian prospective observational study, aimed at evaluating of the clinical results early using injections of abobotulinumtoxinA (Abo-BTA, Dysport®) in patients with upper limb spasticity (ULS), which is one of disabling consequence traumatic's brain injuries (TBI). Currently, botulinum therapy is an integral part of the complex treatment of patients with chronic spasticity, has a high level of evidence (level IA), is included in clinical recommendations, national guidelines in a lot of countries around the world countries. The article analyzes results of studies conducted in the world in recent years, which confirm the effectiveness of Abo-BTA injections in the treatment of spasticity, which developing in early period after acute brain injury. Presented data of their own observations are allowed to authors conclude, that using of Abo-BTA injections in the complex rehabilitation of patients with ULS in the early recovery period of TBI demonstrates its good tolerability and a high safety profile, contributes to improving the effectiveness of treatment by reducing muscle tone and spasticity, increasing the volume of movements in joints. Therefore, Abo-BTA injections can be considered as a necessary addition to standard early rehabilitation programs. However, it is necessary to conduct further large-scale studies to more accurately determine the timing of the start of botulinum therapy, the doses of Abo-BTA, the most effective combinations of rehabilitation methods in the creating of individual programs.