Real-world Observational Study Research Articles

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study

ObjectivePerampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4–18 years) with epilepsy. MethodA multicenter prospective observational study was performed on children and adolescents (age, 4–18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. ResultsIn this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. ConclusionThe overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

A Real-World Observational Study to Evaluate the Safety and Effectiveness of Fluticasone Furoate-Oxymetazoline Fixed Dose Combination Nasal Spray in Patients with Allergic Rhinitis.

Allergic rhinitis (AR) has shown an increasing prevalence leading to a considerable medical and social burden. Nasal congestion is the cardinal symptom of AR, and the upper respiratory tract is most affected by this long-lasting ailment. Intranasal corticosteroids alleviate nasal congestion, along with other symptoms of AR, but their effect is not evident immediately. Oxymetazoline has a rapid onset of action, but its use should be limited to 3-5days. The study aimed to evaluate the safety and effectiveness of the fixed-dose combination nasal spray containing fluticasone furoate and oxymetazoline hydrochloride (FF+OXY) 27.5/50mcg once daily in patients with AR in a real-world clinical setting. The study was a prospective, open-label, single-arm, multicenter, real-world observational study conducted in patients with AR for a period of 28days. Patients (n=388) with a diagnosis of AR were treated with a combination of FF+OXY nasal spray. Total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total symptom score (TSS) were documented at baseline and at the end of study period. The overall effectiveness of treatment with FF + OXY was rated by the investigators as very good/good/satisfactory/poor (4-point Likert scale) for each patient. Treatment with FF+OXY resulted in significant reduction in the TNSS, TOSS and TSS, from 7.18±3.38 at baseline to 0.20±0.84 (p<0.001), from 2.34±2.29 at baseline to 0.09±0.53 (p<0.001), from 9.51±4.94 at baseline to0.29±1.32 (p<0.001) at 28days respectively. With respect to effectiveness, the investigators reported very good effectiveness in 52.12% of patients. No serious adverse events were reported. The fixed-dose combination of once-daily fluticasone furoate and oxymetazoline hydrochloride nasal spray 27.5/50mcg was effective in relieving the nasal congestion and reduction of TNSS, TOSS and TSS in patients suffering from AR. The combination was safe and well tolerated with no rebound congestion throughout the treatment period.

Factors associated with sex differences in viral non-suppression in the Swedish InfCareHIV cohort: An observational real-world study.

Women living with HIV are underrepresented in clinical trials assessing outcomes of antiretroviral treatment (ART), justifying the need for observational studies. We investigated differences in viral non-suppression between women and men in the Swedish InfCareHIV cohort and analysed results in relation to biological and socio-demographic variables and patient-reported outcome measures (PROMs). The study included people living with HIV (PLWH) aged ≥18 years, who initiated ART at least 6 months prior to inclusion. Data from the InfCareHIV registry 2011-2018 were collected. Associations between variables and HIV RNA ≥50 copies/mL were investigated in uni- and multivariable analyses using generalized estimating equations, providing relative risks (RRs) as effect size. The study included 38% (n = 2981) women. Women were more likely to have HIV RNA ≥50 copies/mL than were men [RR = 1.20, 95% confidence interval (CI): 1.10-1.31]. After adjusting for origin and route of transmission, sex at birth was no longer associated with viral non-suppression. PROMs were available in 52.4% of PLWH, and items associated with viral non-suppression were impaired adherence in women (RR = 2.38, 95% CI: 1.79-3.17) and men (RR 1.84, 95% CI: 1.40-2.42), and experience of side effects in women (RR = 1.49, 95% CI: 1.10-2.02). This observational study found a 20% higher relative risk of viral non-suppression in women than in men and the difference was associated with socio-demographic factors. The associations between PROMs and viral non-suppression varied between women and men. PROMs are important health outcomes that may identify PLWH in need of support to achieve viral non-suppression.

Impact of lipodystrophy on health-related quality of life: the QuaLip study

BackgroundLipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits.ResultsEighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive–compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive–compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects.ConclusionsLipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy.

A real-world, cross-sectional, and longitudinal study on high-risk human papillomavirus genotype distribution in 31,942 women in Dongguan, China.

Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology. From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology. In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group. The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Efficacy and safety of belimumab in patients with lupus nephritis: a real-world retrospective observational study.

To evaluate the differences in efficacy and safety between Lupus Nephritis (LN) patients who received belimumab plus standard therapy and those who received only standard therapy in real world practice. Patients diagnosed with LN at the First Affiliated Hospital of Wenzhou Medical University from November 2012 to July 2023 were identified, and eligible cases were divided into two groups according to whether they received additional treatment with belimumab during the course of the disease. A total of 1,169 LN patients were identified from our follow-up database. 112 patients receiving add-on treatment with belimumab (BLM group) and 112 control patients matched for relevant baseline characteristics were enrolled in this study. The median duration of treatment with belimumab was 13.82 [7.24, 20.29] months. Compared with the control group, the BLM group had more significant improvement in disease activity indicators such as serum albumin and complement levels, significantly lower B cell count, immunoglobulin, and earlier first attainment of renal remission, but there was no significant improvement in renal function and kidney-related events or death during the 2-year follow-up period. In the BLM group, the treatment effect of belimumab was more prominent in patients with lower levels of proteinuria. The safety profile of belimumab treatment was favorable, with a lower incidence of respiratory tract infection in the BLM group than in the control group during the follow-up period (p= 0.015). This real-world study revealed that add-on treatment with belimumab provided better disease remission, and the therapeutic effect was more significant in patients with lower proteinuria levels. In addition, it had a favorable safety profile and reduced the risk of respiratory tract infection.

A real-world observational study assessing relationships between excessive daytime sleepiness and patient satisfaction in obstructive sleep apnea

Objectives/BackgroundTo estimate prevalence and severity of excessive daytime sleepiness among patients with obstructive sleep apnea (OSA) who were prescribed treatment; assess perception and satisfaction of OSA-related care; describe relationships between excessive daytime sleepiness, treatment adherence, and patient satisfaction. Patients/methodsA national population-based cross-sectional sample of US adults with clinician-diagnosed OSA was surveyed in January 2021 via Evidation Health's Achievement App. Patients completed the Epworth Sleepiness Scale, rated satisfaction with healthcare provider and overall OSA care, and reported treatment adherence. Covariates affecting excessive daytime sleepiness (average weekly sleep duration, treatment adherence, sleepiness-inducing medications, age, sex, body mass index, nasal congestion, smoking status, and comorbidities) were adjusted in multivariate regression models. ResultsIn 2289 participants (50.3 % women; 44.8 ± 11.1 years), EDS was highly prevalent (42 %), and was experienced by 36 % of patients with high positive airway pressure (PAP) therapy adherence. Each additional hour of nightly PAP use was associated with improved sleepiness (a 0.28-point lower Epworth score; p < 0.001). Excessive daytime sleepiness was associated with lower patient satisfaction with healthcare providers and overall care (OR [95 % CI] 0.62 [0.48–0.80] and 0.50 [0.39–0.64], respectively; p < 0.0001), whereas PAP adherence was associated with higher patient satisfaction (OR [95 % CI] 2.37 [1.64–3.43] and 2.91 [2.03–4.17]; p < 0.0001), after adjusting for confounders. ConclusionsIn a real-world population-based study of patients with OSA, excessive daytime sleepiness was highly prevalent and associated with poor patient satisfaction ratings. Better patient-centered care among patients with OSA may require interventions aimed at addressing excessive daytime sleepiness and treatment adherence.

Effectiveness and safety of adalimumab in patients with intestinal Behçet’s disease: a real-world prospective observational study in South Korea

BackgroundIntestinal Behçet’s disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab.MethodsThis was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet’s disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs).ResultsA total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002).ConclusionAdalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.

Conversion surgery for initially unresectable hepatocellular carcinoma using lenvatinib combined with TACE plus PD-1 inhibitor: A real-world observational study

BackgroundConversion therapy for initially unresectable hepatocellular carcinoma (iuHCC) using lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus a PD-1 inhibitor (LTP) has achieved promising results. However, further comparative research is necessary to evaluate the effectiveness and safety of conversion surgery (CS) for iuHCC. MethodsData for 32 consecutive patients with iuHCC receiving CS and 419 consecutive patients with resectable HCC receiving initial surgery (IS) between November 2019 and September 2022 were collected retrospectively. After propensity score matching (PSM), 65 patients were selected. ResultsBefore matching, the CS group had longer EFS (not reached vs. 12.9 months, P < 0.001) and similar OS (not reached vs. not reached, P = 0.510) compared with the IS group. Similar results for EFS (P = 0.001) and OS (P = 0.190) were obtained after matching. The multivariable Cox model (HR = 0.231, 95% CI: 0.105–0.504; P < 0.001) and subgroup analyses confirmed that CS could improve EFS. The CS group had significantly lower incidence of microvascular invasion (MVI) than the IS group (3.1% vs. 50.4%, P < 0.001). Moreover, the two groups had similar safety profiles. ConclusionsCS is effective and safe for patients with iuHCC receiving LTP. LTP has the potential to reduce risk factors for postoperative recurrence, especially MVI, which may influence surgical decision-making.

Using Conversational AI to Facilitate Mental Health Assessments and Improve Clinical Efficiency Within Psychotherapy Services: Real-World Observational Study.

Most mental health care providers face the challenge of increased demand for psychotherapy in the absence of increased funding or staffing. To overcome this supply-demand imbalance, care providers must increase the efficiency of service delivery. In this study, we examined whether artificial intelligence (AI)-enabled digital solutions can help mental health care practitioners to use their time more efficiently, and thus reduce strain on services and improve patient outcomes. In this study, we focused on the use of an AI solution (Limbic Access) to support initial patient referral and clinical assessment within the UK's National Health Service. Data were collected from 9 Talking Therapies services across England, comprising 64,862 patients. We showed that the use of this AI solution improves clinical efficiency by reducing the time clinicians spend on mental health assessments. Furthermore, we found improved outcomes for patients using the AI solution in several key metrics, such as reduced wait times, reduced dropout rates, improved allocation to appropriate treatment pathways, and, most importantly, improved recovery rates. When investigating the mechanism by which the AI solution achieved these improvements, we found that the provision of clinically relevant information ahead of clinical assessment was critical for these observed effects. Our results emphasize the utility of using AI solutions to support the mental health workforce, further highlighting the potential of AI solutions to increase the efficiency of care delivery and improve clinical outcomes for patients.

Real-world observational study on the long-term effect of L-glutamine treatment on renal parameters of adult and pediatric patients with sickle cell disease.

Sickle cell disease (SCD) is a rare genetic blood condition affecting millions worldwide. Oxidative stress is a key player in the pathogenesis of SCD and its comorbid consequences. Renal function impairment is a common complication of SCD in both pediatric and adult patients with serious consequences leading to increased risk of mortality. In this observational real-world study, we are reporting the long-term (120 weeks) renal function in 10 patients treated with L-glutamine. Ten patients (4 pediatric and 6 adults), with confirmed diagnoses of SCD (HbSS genotype), were enrolled, these included four patients from Qatar with Arab Indian haplotype and six patients from French Guiana with African haplotype. All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 120 weeks. Clinical events and laboratory parameters (renal function, hemoglobin, reticulocytes, and lactate dehydrogenase [LDH]) were measured at baseline, 48, and 120 weeks. The study showed that with L-glutamine treatment there were improvements in renal and hematological parameters with no vaso-occlusive crisis at both 48-and 120-week follow-up time points in all 10 patients. Improvements were seen in the albumin creatinine ratio (ACR) from baseline to 48 weeks (mean [Standard deviation SD] ACR: -4.19 [9.81] mg/g) and 120 weeks (mean [SD] ACR: -12.31 [21.09] mg/g). Mean (SD) increase in hemoglobin concentrations from baseline to 48 weeks and 120 weeks was 0.72 (1) g/dL and 1.41 (0.79) g/dL, respectively. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 48 weeks (mean [SD] change from baseline to 48 weeks, reticulocyte counts: -40.30 [101.58] × 109 cells/L; LDH levels: -259 [154.93] U/L) and 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -58.30 [128.38] × 109 cells/L; LDH levels: -344.80 [274.63] U/L). This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment.

Coagulation Function and Type 2 Diabetic Kidney Disease: A Real-World Observational Study

Objectives. Type 2 diabetic kidney disease (DKD), a chronic microvascular complication of diabetes, may exhibit a complex interrelation with coagulation function. This study is aimed at elucidating the association between coagulation function and DKD. Methods. This was a real-world observational study conducted in Beijing, involving 2,703 participants. All patients with diabetes were classified into two groups, viz., DKD and non-DKD groups. Effect magnitudes are denoted as odds ratios (OR) with a 95% confidence interval (CI). To mitigate potential bias in group comparisons, we employed propensity score matching (PSM). Results. After adjusting for variables such as age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), triglyceride (TG), c-reactive protein (CRP), platelet (PLT), and serum albumin (sALB), it was discerned that fibrinogen (FIB) (OR, 95% CI, P : 1.565, 1.289-1.901, &lt;0.001) and fibrinogen degradation products (FDP) (1.203, 1.077-1.344, 0.001) were significantly correlated with an increased risk of DKD. To facilitate clinical applications, a nomogram prediction model was established, demonstrating commendable accuracy for DKD prediction. Conclusions. Our findings suggest that elevated levels of FIB and FDP serve as potential risk indicators for DKD, and coagulation function may play an important role in the occurrence and development of DKD.

Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study

BackgroundObservational studies have indicated a potential association between autoimmune diseases and the occurrence of sepsis, with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.MethodsIn the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for sepsis and its 28-day mortality were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and sepsis and its 28-day mortality. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and sepsis. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as 28-day mortality of sepsis using a real-world database (the MIMIC-IV database). A cohort of 2537 patients diagnosed with autoimmune disease were extracted from the database for analysis. Multivariable logistic regression models were used to confirm the association between autoimmune diseases and the occurrence of sepsis, as well as the 28-day mortality associated with sepsis.ResultsIn univariable MR analysis, there appeared to be causal relationships between genetically predicted type 1 diabetes (OR = 1.036, 95% CI = 1.023–1.048, p = 9.130E-09), rheumatoid arthritis (OR = 1.077, 95% CI = 1.058–1.097, p = 1.00E-15) and sepsis, while a potential causal link was observed between celiac disease and sepsis (OR = 1.013, 95% CI = 1.002–1.024, p = 0.026). In a subsequent multivariable MR analysis, only rheumatoid arthritis was found to be independently associated with the risk of sepsis (OR = 1.138, 95% CI = 1.044–1.240, p = 3.36E-03). Furthermore, there was no causal link between autoimmune disorders and 28-day mortality from sepsis. In reverse MR analysis, sepsis was suggested to potentially trigger the onset of psoriasis (OR = 1.084, 95% CI = 1.040–1.131, p = 1.488E-04). In the real-world observational study, adjusting for multiple confounders, rheumatoid arthritis (OR = 1.34, 95% CI = 1.11–1.64, p = 0.003) and multiple sclerosis (OR = 1.31, 95% CI = 1.03–1.68, p = 0.02) were associated with a higher risk of sepsis. In addition, we did not find that autoimmune diseases were associated with 28-day mortality from sepsis.ConclusionBoth in observational and MR analysis, only rheumatoid arthritis is highly correlated with occurrence of sepsis. However, autoimmune disease was not associated with an increased 28-day mortality in patient with sepsis. Sepsis may increase the risk of developing psoriasis.

Antiresorptive injections reduce refracture incidence in elderly spinal or hip fractures: A real-world observational study

Antiresorptive injections reduce refracture incidence in elderly spinal or hip fractures: A real-world observational study

S151 Biologic Therapy Sequencing in Ulcerative Colitis: A Real-World Observational Study of Second-Line Therapy After Vedolizumab

S151 Biologic Therapy Sequencing in Ulcerative Colitis: A Real-World Observational Study of Second-Line Therapy After Vedolizumab

Effect of Ursodeoxycholic Acid for Sars-Cov-2 Prevention in Hematological Malignancies: An Observational Real-World Study

Introduction: Disease-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).After the adjustments and optimizations of Chinese control strategies and policies for COVID-19 on December of 2022, clinical exposure increased rapidly.There are greater concerns for patients with hematological malignancies, particularly those who have undergone hematopoietic stem cell transplantation (HSCT). One promising preventive measure that has recently gained attention is ursodeoxycholic acid (UDCA). This drug is mainly used to treat biliary tract disease and other hepatobiliary disorders, particularly primary biliary cholangitis (Hirschfield GM, et al. Gut 2018); and also has been widely used at a higher dosage to prevent sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) after HSCT in the clinical setting. Recently, Brevini et al. demonstrated that UDCA downregulated ACE2 expression by reducing farnesoid X receptor signaling, resulting in reduced SARS-Cov-2 infection (Brevini T, et al. Nature 2022), indicating that pharmacological prophylaxis using UDCA against COVID-19 in vulnerable groups was feasible, but the clinical data to support this practice is limited. Therefore, we aim to present epidemiological data for Chinese patients with hematological malignancies during this epidemic wave, and investigate the protection effects offered by UDCA against COVID-19 in these patients. Methods: This investigation was a single-center, observational real-world study, and was granted by the ethics committee of the Institute of Hematology &amp; Blood Diseases [No. QTJ2023012-EC-1]. The transplant patients were included in the “NICHE-SKIRT” project (Cao Y, et al. Am J Hematol 2023). Informed consent for the acquisition and the use of patient samples was obtained. Data for hospitalized patients at the Institute of Hematology &amp; Blood Diseases Hospital (Tianjin, China) was reviewed between December 2022 and January 2023. COVID 19 status was assessed using hospital-reported PCR and/or antigen tests for twice a week. We analyzed follow-up records up to 14th February 2023. The primary end-point was the rate of COVID -19 infection. Results: We enrolled 393 patients with a median age of 38 years old. At the cutoff date, 297 patients (75.6%) had confirmed COVID-19 infection (72.5% in the allo-HSCT cohort). Among the 273 evaluable patients, the majority (64.8%) had asymptomatic/mild disease. The severe/critical patients accounted for only 15.8%. Seven hospitalized patients had died from COVID-19 by the last follow-up date. The median period between COVID-19 diagnosis and death was 15 days (range: 2-32 days). Lower proportion of CD3+CD4+T cells associated with more severe COVID-19 clinical spectrum (Asymptomatic/mild [n = 97] moderate [n = 46], adjusted P = 0.001; Asymptomatic/mild vs. severe/critical [n = 25], adjusted P = 0.036). Among these patients, 163 received UDCA (UDCA group) while 230 did not (non-UDCA group). The COVID-19 infection rate was lower in the UDCA group (69.9% vs. 79.6%; P= 0.039). However, patients in the UDCA group had a higher ECOG score and Charlson Comorbidity Index (Table 1), suggesting that they were more likely to have underlying health conditions. To account for this potential bias, we performed PSM, which confirmed that the UDCA group had a significantly lower rate of COVID-19 infection compared to the non-UDCA group (69.0% vs. 81.0%; P = 0.049) in the validated cohort. Univariate logistic regression analysis showed that only UDCA administration was associated with COVID-19 infection (OR: 0.598; P = 0.029). To further investigate the effect of UDCA in specific populations, we carried out an exploratory analysis. Our results suggest that males, patients with a CCI ≥ 2, a history of smoking, and those with acute lymphoblastic leukemia (ALL) may benefit the most from the protective effect of UDCA against COVID-19. Conclusion: This study aimed to investigate the prevalence and clinical outcomes of SARS-CoV-2 infections in Chinese patients with hematologic disorders during the COVID-19 epidemic that began at the end of 2022. Our findings provide support for preclinical studies suggesting that UDCA may have marginal benefit in protecting against COVID-19. However, prospective studies with a higher dose of UDCA need to be performed.

Second Line Treatment and Outcomes of Patients with Multiple Myeloma: A Real World Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

Introduction: The treatment of multiple myeloma (MM) has evolved rapidly, with various combinations of immunomodulators (IMiDs), proteasome inhibitors (PIs), corticosteroids and autologous stem cell transplantation (ASCT) utilized in newly diagnosed (ND) patients; in some jurisdictions, monoclonal antibodies (MABs) are also incorporated in first-line treatment. Over the last decade, the standard of care in Canada for NDMM in fit younger patients has consistently been induction (CyBorD/more recently RVD) followed by ASCT and maintenance lenalidomide (len) until progression. In transplant-ineligible patients, bortezomib- or len-based treatments in doublets or triplets have been used frontline. At relapse, options have included re-induction followed by 2nd ASCT or doublet/triplet combinations until progression. Limited comparative data are available to support any one approach. The aim of this retrospective study was to assess the treatment patterns and outcomes of MM patients treated at 1st relapse in a real-world setting. This data may be useful to myeloma stakeholders when evaluating the potential impact of even newer novel immunotherapeutic agents in patients in who have had 1 prior line of treatment. Methods: We performed a retrospective observational study using the Canadian Myeloma Research Group Database (CMRG-DB), which is a prospectively maintained disease-specific database with ≥ 9000 patients enrolled from 16 academic sites across Canada. All MM patients who initiated second-line therapy between 01/12/2010 - 30/06/2022 were included and results were analyzed up to 23/05/2023. We aimed to evaluate the following outcomes for each second-line regimen: overall response rate (ORR), progression-free survival (PFS) and overall survival (OS), calculated from the start of second-line therapy. Survival was estimated using Kaplan-Meier methods and compared between groups using the log rank test. Results: A total of 3569 patients were identified: 1638 (45.9%) who had prior ASCT and 1931 (54.1%) non-ASCT patients. 2715 (76%) patients were bortezomib-exposed in first line, 1052 (30%) were lenalidomide-exposed; 22% had high-risk cytogenetics. The most commonly used second-line regimens were Rd in 1325 (37%) of patients, DRd in 346 (10%), CyBorD in 291 (8%), 2nd ASCT in 270 (8%), RVd in 201 (6%) and DVd in 167 (5%). Outcomes including ORR, ≥ VGPR rate, PFS and OS from second-line treatment for regimens with &amp;gt;50 patients are presented in Table 1. Among all patients, the highest ORRs were seen with DRd (90%), 2nd ASCT (89%), Kd/KCd (79%), RVd (78.1%) and KRd (74%); DRd had the highest ≥ VGPR rate (66%). In patients who had received bortezomib-based first line treatment, the second line ORRs were 96%, 98% and 95% for VRd, KRd and DRd, respectively, with a corresponding median PFS of 20 months (VRd), 19 months (KRd) and 28 months (DRd). For patients who had len-based first line treatment, the second line ORRs were 80% for Kd/KCd and 95% for DVd with a median PFS of 16 months (Kd/KCd) and 11 months (DVd), respectively. The median PFS was 41 months after 2 nd ASCT; of these patients, 68% were exposed to bortezomib in first line and 34% were len exposed in first line. The median PFS was 30 months in those who had len maintenance after their 1 st transplant compared to 60 months in those with no initial maintenance. Conclusion: In this real-world observational study we demonstrate that Canadian patients achieved results comparable those noted in prospective clinical trials leading to the approval of these agents in the second-line setting. Triplet combinations with an IMID backbone, including DRd, KRd and Ixa-Rd, had high response rates, with DRd offering the longest PFS. Patients undergoing 2 nd ASCT had ORRs and PFS comparable to DRd, although these results were likely influenced by selection of a population with a favorable response to 1st ASCT . Given the expanding use of IMID, PI and MAB combinations in first-line, our results highlight the need for better modalities at the time of 1 st relapse. Earlier integration of “novel” agents, including CAR-T therapy, bi-specifics, conjugated antibodies and CEL-MoDs-even in the second-line setting–is likely required to improve on these outcomes. The current analysis provides efficacy benchmarks to guide their implementation. Financial Support: CMRG received financial support from Janssen Inc. for the conduct of this study

Update for the ‘Watch’ Registry, a Real-World Observational Study Using Clonoseq® to Monitor MRD in Lymphoid Malignancies

Background: For patients with the most common B-cell malignancies, assessment of minimal/measurable residual disease (MRD) is routinely incorporated into clinical trials to evaluate patient response and NCCN guidelines include recommendations for incorporation of MRD assessment into clinical practice for ALL, CLL, and MM. Despite that, there is a desire for additional data that reflect the impact of MRD assessment in patient management in the real-world setting. The Watch Registry (NCT04545333) is a prospective, multicenter observational study being conducted in the US to collect data from health care providers who use the clonoSEQ MRD assay as part of routine care for their lymphoid malignancy patients. Data collection is focused on understanding broad practice patterns for clonoSEQ® MRD assessment, including assay timing and subsequent treatment decisions. The ultimate goal of the study is to describe the implementation and impact of the assay in patient management. Here we describe the latest updates from this ongoing study. Methods: Eligible patients are ≥ 18 years old, diagnosed with NHL, MM, ALL, or CLL, not enrolled in an interventional clinical study that dictates the frequency of their MRD testing, and whose treating physician is currently or planning to use clonoSEQ to monitor their MRD as part of their routine management. Patients may be in any phase of treatment at enrollment. Enrollment is now closed and follow-up will continue through December 31, 2024. Results: From October 2020 through data cutoff of June 21, 2023, 465 patients were enrolled across 18 academic and community sites (463 patients with reportable data). Enrollment by disease is 70 ALL, 109 CLL, 140 MM, 34 DLBCL, 27 MCL, 54 FL and 29 other lymphoid malignancies. Of these patients, 91 (20%) have discontinued the study; the most common reasons are death (35; 8%) and failure to detect trackable sequences by clonoSEQ (23; 5%). Other reasons include site closure and patient/physician decision to withdraw. Patients range in age from 18 to 92, 57% are male, and the mean lines of therapy (LOT) prior to enrollment is ~2. The median follow up period is 14 months. To date, 994 clonoSEQ MRD tests have been ordered and 74.5% of patients have received at least 1 MRD test (Table 1). The most frequent testing was reported for ALL patients (4.8 tests/pt) followed by CLL (2.9 tests/pt), MCL (3.3 tests/pt), other lymphoid malignancies (2.9tests/pt), DLBCL (2.6 tests/pt), FL (2.1 tests/pt) and MM (2.2 tests/pt). Across all disease cohorts, most MRD tests were ordered during remission (71.4%). In the ALL cohort, a larger proportion of tests were ordered at other treatment timepoints relative to other disease cohorts: end of induction (6%), pre-HSCT (6%), post-HSCT, including some post-HSCT monitoring (42%) and post-CAR-T (6%). Across all cohorts, 220 patients (48%) had multiple MRD tests ordered with the largest proportion observed in the ALL cohort (67%), followed by MCL (63%), DLBCL (50%), CLL (48%), other lymphoid malignancies (45%), MM (39%) and FL (35%). For patients tested during monitoring, the number of tests/pt was generally larger among patients with ≥1 prior LOT compared to patients with 0 prior LOT. With 979 test results reported (Table 2), there were 583 tests with residual sequences detected (59.5%) and 396 with no residual sequences detected (39.5%). Based on the presence of residual sequences, a change to a patient's treatment plan was reported 66 times (11.3%) and there were 52 separate reports (11.1%) of a change to the frequency of future MRD monitoring. Specific treatment changes included 56 instances of therapy intensification (9.6%) and 10 instances of therapy de-intensification (1.7%). In the case where no change was made based on the presence of residual sequences, reported reasons for not making a change (if reported) included decreasing MRD (24%) and low/stable disease (10.9%). Conclusions: Clinicians are using clonoSEQ to assess MRD across multiple lymphoid malignancies in routine care. In ALL, MRD testing was reported for multiple treatment timepoints whereas in other disease states (CLL, MM, NHL) reported use of the assay was predominantly for monitoring remission. The advent of therapeutic regimens for B-cell malignancies with higher relative response rates denotes the need for sensitive tools that can be used in clinical practice to better assess treatment response and monitor MRD to facilitate future treatment decisions.

1607. Clinical Outcomes at Month 6 after Initiation of Cabotegravir and Rilpivirine Long-Acting (CAB + RPV LA) in an Observational Real-World Study (BEYOND)

Abstract Background CAB+RPV LA is the first complete long-acting regimen for virologically suppressed people with HIV (PWH) and demonstrated non-inferiority to standard of care antiretroviral regimens in the Phase 3/3b trials FLAIR, ATLAS, ATLAS-2M, and SOLAR. Implementation of a provider administered regimen poses new delivery challenges and real-world evidence is essential to understand utilization and clinical outcomes. The BEYOND study describes the demographics and month 6 (M6) clinical outcomes of patients initiating CAB+RPV LA in the US. Methods BEYOND is a 2-year observational real-world study of utilization, outcomes, and experience of people with HIV (PWH) initiating CAB+RPV LA (monthly or every 2 months) across 30 US sites. Healthcare providers (HCPs) completed an electronic case report form (eCRF) at baseline and M6 to capture demographics, medical and treatment history, and clinical outcomes. Results A total of 308 PWH (Table 1) were enrolled between Sep 2021- Jul 2022 and initiated on CAB+RPV LA. As of the data cut-off for this analysis (Jan 2023), 248 PWH had reached M6 of which 25 were reported as having discontinued CAB+RPV LA. The most common HCP reported primary reason for initiating CAB+RPV LA was patient request (41%). At M6, of the 803 injections given after the first injections, 667 (83%) occurred within +/-7 days of the target treatment date and 136 (17%) were outside the target treatment window (median 4 days outside). Of 1087 total injections expected, 44 (4%) were missed; of these, 3 (7%) used oral CAB+RPV and 19 (44%) used other oral regimens to cover missed injections. Of 189 PWH with viral load data available at both baseline and M6 (Table 2), 181 (96%) had viral loads of &amp;lt; 50 copies/mL. Confirmed virologic failure (CVF) occurred in 4 (1.6%), including 1 who had missed injections. Resistance was reported in 2 PWH. Discontinuations due to drug intolerance/injection site reactions were reported in 6 PWH. Conclusion The M6 results from real world initiation of CAB+RPV LA in the US are consistent with the Phase 3/3b clinical trials with high rates of virologic suppression, low rates of CVFs and treatment emergent resistance, and low rates of discontinuation due to drug intolerance. Disclosures Gary I. Sinclair, MD, Abbvie: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Thera: Advisor/Consultant|Thera: Grant/Research Support|Thera: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Alexandra Dretler, MD, Gilead: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Pfizer: Stocks/Bonds Stefan Schneider, MD, ViiV Healthcare: Grant/Research Support Catherine K. Schubert, PharmD, GSK: Stocks/Bonds|ViiV Healthcare: Employee of ViiV Healthcare Deanna Merrill, PharmD, MBA, AAHIVP, ViiV Healthcare: Employment|ViiV Healthcare: Stocks/Bonds Cindy Garris, MS, GSK: Stocks/Bonds|ViiV Healthcare: Employee