Months Of Treatment In Patients Research Articles

Overview of Urine Cylinders in Patients With Pulmonary Tuberculosis Undergoing Advanced First-Line Treatment at the RSUD Ciamis

Background & Objective: Pulmonary tuberculosis is a contagious disease caused by Mycobacterium tuberculosis bacteria that can attack various organs, especially the lungs. Tuberculosis patients are treated with anti-tuberculosis drugs such as rifampicin and streptomycin, which can potentially cause kidney function impairment. To detect any abnormalities in the kidneys, a urine sediment examination is conducted, which can identify an increase in urine cylinders if any damage to the kidneys is present. This study aims to provide insights into urine cylinders in patients with pulmonary tuberculosis based on the duration of their treatment. Method: This is a descriptive study that utilised a purposive sampling technique. The study involved 38 Tuberculosis patients as respondents. Sampling was carried out at the DOTS clinic of RSUD Ciamis and the research was conducted between October 2021 and May 2022. Result: Out of 38 samples, 6 people tested positive for cylinders at a value of +1 (which means very little). These cylinders included hyaline, wax, granule, fat, and epithelial cell cylinders. The percentage of people who tested positive for cylinders was 15.8%. On the other hand, 32 people tested negative for cylinders, which accounts for 84.2% of the total sample. Conclusion: It can be concluded that cylinders were found in tuberculosis patients. Future researchers are advised to examine urine cylinders in pulmonary tuberculosis patients undergoing the sixth month of treatment in patients at a young age.

Hematocrit control and thrombotic risk in patients with polycythemia vera treated with ruxolitinib in clinical practice.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production resulting in elevated hemoglobin and/or hematocrit levels. Patients often have symptoms such as fatigue, pruritus, and painful splenomegaly, but are also at risk of thrombosis, both venous and arterial. Ruxolitinib, a selective Janus kinase inhibitor, is approved by the US Food and Drug Administration as second-line cytoreductive treatment after intolerance or inadequate response to hydroxyurea. Although ruxolitinib has been widely used in this setting, limited data exist in the literature on ruxolitinib treatment patterns and outcomes among patients with PV in routine clinical practice. We report a retrospective, observational, cohort study of patients treated for PV with ruxolitinib across three US centers (academic and regional practice) from December 2014-December 2019. The study included 69 patients, with a median follow-up duration of 3.7 years (95% CI, 2.9-4.4). Our data demonstrate very high rates of hematocrit control (88% of patients by three months and 89% by six months); few patients required dose adjustments or suspension. No arterial thromboses were observed; however, the follow-up duration does not allow for the generation of meaningful conclusions from this. Three patients had thrombotic events; one was in the setting of a second malignancy, one post-operative, and a third related to prolonged immobility. We also found that 28% of patients initiated ruxolitinib as a result of poorly controlled platelet counts, second only to hydroxyurea intolerance (46%) as a reason to start therapy. In clinical practice, ruxolitinib continues to be effective in controlling hematocrit levels after three and six months of treatment in patients and is associated with low thrombotic risk.

The Depth of the Molecular Response in Patients with Chronic Myeloid Leukemia Correlates with Changes in Humoral Immunity.

Background and Objectives: The effective treatment of chronic myeloid leukemia leads to the restoration of proper immune system function. We aimed to investigate fluctuations in circulating cytokines, angiogenic factors and complement components in patients with CML during the first year of treatment with TKI and correlate them with the degree of achieved molecular response. Material and Methods: We recruited 31 patients with newly diagnosed CML. Peripheral blood and bone marrow samples were obtained, and concentrations of serum proteins were measured using an immunology multiplex assay. Results: The study cohort was divided into two groups of optimal or non-optimal in accordance with the European Leukemia Net (ELN) guidelines. We found significantly higher concentrations of C1q, C4 and C5a in serum after 3 months of TKI treatment in patients who achieved optimal responses in the 6 months after diagnosis. The most alterations were observed during 12 months of therapy. Patients in the optimal response group were characterized by higher serum concentrations of TGF-β, EGF, VEGF, Angiopoietin 1, IFN-γ and IL-8. Conclusions: The later plasma concentrations of complement components were significantly increased in patients with optimal responses. The changes after 12 months of treatment were particularly significant. Similar changes in bone marrow samples were observed.

Evaluation of inflammatory biomarkers and the ratio of hemoglobin-red cell distribution width in patients with rheumatoid arthritis treated with tumor necrosis factor-alpha inhibitors.

The aim of this study was to examine pre-treatment and post-treatment hemogram-derived inflammatory biomarkers in patients with rheumatoid arthritis (RA) who received anti-tumor necrosis factor (TNF)-α treatment. The data of 1182 patients with RA were screened. Among them, 207 patients who met the eligibility criteria were included in the retrospective study. Demographic parameters, disease activity, and blood cell-derived indexes were evaluated. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and hemoglobin-red cell distribution width (Hb/RDW) rates were evaluated before treatment and at the third month of treatment in patients with RA who received anti-TNF-α treatment. According to the EULAR response criteria, 12.6% of the 207 patients responded to anti-TNF-α treatment as none, 21.3% as good, and 66.2% as moderate, respectively. Post-treatment NLR and PLR values were significantly lower than pre-treatment values (p < 0.001), whereas post-treatment LMR and Hb/RDW values were significantly higher than pre-treatment values (respectively, p = 0.001 and p = 0.012). The difference between pre-treatment and post-treatment values of LMR and Hb/RDW was significantly higher when compared to the moderate + good response groups than the none-response group (p = 0.002 and p = 0.014, respectively). However, in the receiver operating characteristic curve analysis, these parameters were not found to be significant in predicting treatment response. Significant changes were detected in hemogram-derived inflammatory markers of the groups responding to anti-TNF-α treatment. They can be used as a guide during treatment follow-up. Yet, they do not predict treatment response. Key Points • RA may manifest with periods of remission and activation, and regular follow-up is essential. • There is a demand for readily available, reproducible, and cost-effective parameters to assess treatment response. • Hemogram-derived inflammatory markers differ in relation to anti-TNF-α treatment response in RA. • None of those markers demonstrate an acceptable predictive performance in distinguishing patients based on their response to TNF-α inhibitors.

JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib.

Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. Patients with Ph+ CML in the chronic phase (n = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.

Improvements in Patient-Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real-World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Evaluate patient-reported outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. This analysis includes registry participants who initiated and persisted with on-label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (On-Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient-reported outcomes, including patient-reported pain (0-100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0-100 visual analog scale), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3). Unadjusted, nominal P values were calculated via single-proportion, one-sided test (H0 = 0%; α=0.05). Of 90 On-Label Persisters, most had treatment-resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease-modifying antirheumatic drugs, respectively), with mean (SD) baseline patient-reported pain, PtGA, and HAQ-DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9(0.6), respectively. Among those with patient-reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15-mm reductions at 6 months; among those with HAQ-DI scoresof at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P < 0.001). Pain and physical function are important contributors to health-related quality of life. In this real-world population of patients with treatment-resistant PsA and 6 months of persistent guselkumab treatment, clinically meaningful improvements in pain and physical function were achieved by approximately 40% and 30% of patients, respectively.

Tuberculosis Testis In Middle-Aged Male As A Rare Case Of Genitourinary Tuberculosis: A Case Report

Introduction: Testicular tuberculosis is a very rare type of urogenital TB. &#x0D; Case Presentation: A 36 year old man came to the emergency room because of pain in the right testicle accompanied by swelling and discharge. Orchiectomy on the dextra testis was continued with treatment using category 1 OAT for 9 months after the diagnosis was made using anatomic pathology examination.&#x0D; Discussion: The physical examination needs to be done carefully because most general practitioners consider testicular enlargement to be a malignancy. Urogenital tuberculosis requires 6 months of treatment and 9 months of treatment in patients with certain conditions.&#x0D; Conclusion: Prompt and precise diagnosis if testicular TB is necesssary to prevent infertility, the most common complication

High Rates of Thrombotic Events in Newly Diagnosed Multiple Myeloma Patients Enrolled on the Maia Trial

Background. Patients with newly diagnosed multiple myeloma (NDMM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Despite the availability of the IMWG and NCCN VTE prophylaxis guidelines and updated risk stratification models such as SAVED and IMPEDE, the optimal thromboprophylaxis strategy is unknown, especially in the age of modern daratumumab-containing regimens. To continue highlighting the importance of appropriate thromboprophylaxis for patients with NDMM, we performed a post-hoc analysis of the randomized phase 3 MAIA trial to identify rates of venous and arterial thromboembolism. Methods. This retrospective study, carried out under YODA Project #2021-4663, used data from the randomized phase 3 MAIA trial that investigated lenalidomide and dexamethasone (Rd) with or without daratumumab (DRd) in 733 transplant ineligible (TIE) patients obtained from the Yale University Open Data Access (YODA) Project, which has an agreement with JANSSEN RESEARCH &amp; DEVELOPMENT, L.L.C.. Thrombotic events (TE), including both venous and arterial events (V/ATE) were examined with VTE events including deep vein thrombosis (DVT), pulmonary embolism (PE), and superficial thrombophlebitis (SVT). Arterial events (ATE) included cerebrovascular accidents (CVA) defined as hemorrhagic, ischemic, or verebrobasilar strokes. The incidence and time to event of V/ATE were calculated and graded using the CTCAE v4, with Grade 1 representing nonactionable venous thrombosis, Grades 2-4 representing TEs requiring increasing higher levels of medical intervention, and Grade 5 indicating death was a result of the TE. Rates and time to events were compared between the DRd and Rd arms. Results. Of the included patients, median age was 72 years (range 64-72) and 48% were female. There was no signficant difference between baseline characteristics of sex, race, myeloma subtype, presence of high-risk cytogenetics, or ISS staging between patients that experienced a V/ATE event and those that did not. All grade V/ATE events were 18% (66/363) and 19% (70/365) in the DRd and Rd arms, respectively. Of these, most were VTE events in both arms (16%), with G2-4 actionable VTE event rate of 14.9% vs 14.8% for the DRd and Rd arms, respectively. G5 VTE events were 0.2% in both arms (no G5 ATEs). ATE were 2.2% and 2.7% in the DRd and Rd group, respectively, overall constituting a minority of events. The overall PE rate was higher in the DRd than Rd arm, 6.3% vs 4.7%, DVT was more frequent in the Rd arm, 9.6% vs 7.7%, and rates of SVT rates were similar between both arms at 1.9% and 2.2% for the DRd vs Rd arms, respectively (Table 1). Median time to onset of cumulative TEs was longer in DRd vs Rd arm, 7.15 (0.27 - 63.0) vs 4.65 (0.03 - 58.0) months, respectively. Among these, median time to onset of VTE was similar among the groups [6.57 (0.27 - 63.0) vs 4.48 (0.03 - 52.9) months, respectively] while the median time to onset of ATEs was longer in DRd vs Rd arm, 19.8 (1.70 - 26.6) vs 8.3 (0.67 - 58.5) months. The incidence of VTE events persisted past 24 months and incidence of ATE events increased over time (Figure 1). Analysis regarding prophylactic anticoagulation use and rates of TE based on prophylactic regimen are ongoing. Conclusion. This retrospective study reveals the highest reported rates of VTE in any modern therapy dataset. In patients with transplant ineligible NDMM, we show that the TE risk persists past 24 months of treatment in patients on DRd or Rd therapy. Similar to observations in the GRIFFIN trial, the addition of daratumumab did not increase the risk of TE. Our report highlights the critical need for further investigation of optimal prophylactic strategies and their duration for patients with NDMM.

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia

OBJECTIVES: Eltrombopag (EPAG) was initially approved by the U.S. Food and Drug Administration (FDA) as first-line treatment, combined with standard immunosuppressive therapy, for patients older than two years old with severe aplastic anemia (SAA). However, the use of EPAG in children with different types of aplastic anemia (AA), especially non-severe AA (NSAA) has been limited. Therefore, we decided to investigate the efficacy, safety, and pharmacokinetics of EPAG in children with NSAA, SAA, and very severe AA (VSAA). METHODS: A prospective, open-label, observational study was conducted at the Institute of Hematology and Blood Diseases Hospital, Tianjin, China. The efficacy including complete response (CR), partial response (PR), and no response (NR), as well as safety was assessed every three months after the start of treatment. A non-linear mixed-effects population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of EPAG. We explored the exposure-response relationship of EPAG in patients with different types of AA. This study was registered at ClinicalTrials.gov (NCT03844360). RESULTS: A total of 23 AA children with an average age of 7.9 (range of 3.0 - 14.0) years were enrolled in this study for efficacy, safety, and PPK analysis. Fifteen patients had a treatment response (5 had CR and 10 had PR). The response rate was 12.5% after 3 months, 50.0% after 6 months, and 100% after 12 months of treatment for patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty-three blood samples were collected and analyzed to build the PPK model using allometric scaling with fixed exponents. Body weight significantly affected EPAG's apparent clearance and volume of distribution. The mean (range) of the area under the concentration-time curve from time zero to infinity (AUC ∞) was 316 (131 - 809) μg×h /mL. Twenty patients with genotypes were included in the genotype analysis. The apparent clearance of EPAG was significantly higher in allele-T carriers of adenosine triphosphate-binding cassette G2 (ABCG2) (rs2231142, G&amp;gt;T) ( p=0.02). In patients with clinical response, children with NSAA exhibited lower AUC ∞, higher apparent clearance, and higher weight-adjusted apparent clearance than those with SAA or VSAA, although the differences were not significant. CONCLUSIONS: This study enriched the efficacy and safety of EPAG in children with different types of AA. Body weight and ABCG2 genotype significantly influence EPAG clearance. The results may support further individualized treatment of EPAG in children with AA.

Olive extract enriched with hydroxytyrosol improves cardiac and vascular function in patients with stable coronary artery disease: a double-blind, placebo-controlled trial

Abstract Aims We investigated the effect of olive extract enriched with hydroxytyrosol, on vascular and myocardial function markers in patients with stable coronary artery disease (SCAD). Methods In a prospective, cross-over, double-blind, placebo-controlled, clinical trial, 30 patients with stable CAD were randomly assigned to an oral supplement containing olive oil extract enriched with hydroxytyrosol (OOHT) or placebo for one month and then were crossed over to the alternate treatment (placebo or OOHT for one more month). We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography d) Pulse Wave Velocity (PWV) e) oxidative/nitrosative stress and inflammatory biomarkers and blood lipids at baseline and after one month treatment. Results Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.81±0.35 vs 1.77±0.40 μm p=0.04 3.71±2.12 vs 6.51±2.31%, p&amp;lt;0.001;2.37±0.40 vs 2.45±0.41, p=0.030 and 11.03±1.81 vs 11.78±2.34 m/sec, p=0.002), while there was no effect after placebo (p&amp;gt;0.05). Compared to baseline, treatment with OOHT reduced malondialdehyde (MDA) a marker of lipid peroxidation (2.10±1.37 vs 1.69±0.83 mmol/lt, p=0.045), oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p&amp;lt;0.05) in contrast to placebo. There was a parallel improvement of E’ of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p&amp;lt;0.05) but not after placebo. Conclusions Olive extract enriched with hydroxytyrosol improves endothelial and arterial function likely by reducing oxidative and inflammatory burden leading to improved LV diastolic function after one month of treatment in patients with stable CAD.

Experience with the interleukin 6 inhibitor (Olokizumab) in patients with rheumatoid arthritis in real clinical practice: Influence on inflammatory activity and disease outcomes

The aim of the study was to evaluate in real clinical practice the effectiveness of therapy with an interleukin-6 inhibitor (olokizumab) in patients with rheumatoid arthritis (RA) in terms of clinical and laboratory activity of the disease, as well as patient-reported outcomes (PROs). Material and methods. 10 patients with a reliable diagnosis of RA were examined: the average age of the patients was 45.70±17.9 years, the duration of the disease was 9.0 (3.0; 12.0) years. Patients were with moderate or high disease activity: DAS28-ESR – 5.13 (4.34; 5.80) points; CDAI – 30.00 (24.00; 35.00); SDAI – 31.86 (24.36; 38,59). All patients were prescribed treatment with olokizumab (OKZ) at a dose of 64 mg subcutaneously every 4 weeks against the background of therapy with methotrexate, leflunomide, non-steroidal anti-inflammatory drugs and glucocorticoids (GC) (up to 10 mg/day in terms of prednisolone). Three patients had previously received tocilizumab (intravenously once a month at a dose of 8 mg/kg), the administration of which was discontinued for administrative reasons 6–12 months before the appointment of OKZ. The results of treatment were assessed by the dynamics of clinical, laboratory parameters (DAS28-ESR, SDAI, СDAI, CRP, ESR, IgM RF, ACCP) and outcomes assessed by the patients themselves (PROs): HAQ-DI index, general assessment of the health status of patients (OSZB) according to VAS, pain according to VAS; scales FACIT, SF-36. As psychometric methods, the questionnaire “Type of attitude towards the disease (TOBOL)”, the Hospital Anxiety and Depression Scale (HADS), and the Toronto Alexithymic Scale (TAS-26) were used. Observation was carried out before treatment, after 3 and 6 months of therapy. Results. Against the background of OKZ therapy, after 3 and 6 months, compared with the baseline, there was a significant decrease in the clinical indices of RA activity: DAS28-ESR – 5.13 (4.34; 5.80), 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10) points respectively; CDAI – 30.00 (24.00; 35.00), 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0) points respectively; SDAI – 31.86 (24.36; 38.59), 11.05 (6.07; 16.07) and 10.17 (7.02; 15.02) points respectively; CRP – 14.30 (7.00; 24.70), 0.70 (0.40; 0.90) and 0.65 (0.20; 3.0) mg/l respectively. No significant dynamics of ESR, RF IgM and ACCP was noted. After 3 and 6 months of treatment with OKZ, there was a significant decrease in OSZB and pain severity according to the VAS scale, and an improvement in the functional state of patients was observed according to the HAQ-DI questionnaire of fatigue indicators (FACIT-F) (p&lt;0.05). The physical component of the SF-36 scale increased significantly only by the 6th month of therapy (p&lt;0.01), while the mental component did not undergo significant changes (p&gt;0.05). In the process of treatment of OKZ, the attitude of patients to the disease changed from the ergopathic, neurasthenic and sensitive components in the TOBOL profile, before it began, then by its end, the dominant ones were harmonious, ergopathic and sensitive profiles. In addition, starting from the 3rd month of treatment in patients with RA, an adaptive response to the disease prevailed. A decrease in the level of anxiety was revealed, compared with the baseline, after 3 and 6 months of observation, depression indicators did not change significantly. Conclusion. In general, the results of this study indicate the effectiveness of ICD in RA, not only in terms of reducing the clinical and laboratory activity of the disease, but also in terms of outcomes reported by the patient himself, characterizing the quality of life and the psycho-emotional state of patients.

SAT656 Weight Reduction After 6 Months Of Setmelanotide Treatment In Patients With Hypothalamic Obesity

Abstract Disclosure: C.L. Roth: Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Received payments from Rhythm Pharmaceuticals, Inc and Saniona for advisory boards and lectures. Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. M. Gottschalk: Advisory Board Member; Self; Received compensation for consulting and participation on advisory boards from Rhythm Pharmaceuticals, Inc. Other; Self; Received funding for clinical trials from Rhythm Pharmaceuticals, Inc. J. Miller: Other; Self; Received research support from Harmony Biosciences, Rhythm Pharmaceuticals, Inc, Soleno Therapeutics, and Tryp Therapeutics. G. Yuan: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. S. Malhotra: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Stockholder in in Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. M. Abuzzahab: Advisory Board Member; Self; Received compensation for advisory board participation from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Consulting Fee; Self; Received compensation for consulting from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Speaker; Self; Received compensation for speaking engagements from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Other; Self; Received research support from Ascendis, Levo Pharmaceuticals, Lumos, NovoNordisk, Rhythm Pharmaceuticals, Inc, Saniona, and Soleno. Background: Hypothalamic obesity (HO) is an acquired form of severe obesity characterized by rapid and excessive weight gain resulting from insult to the hypothalamus—primarily caused by tumor invasion, resection, or radiotherapy—that can impair melanocortin-4 receptor (MC4R) pathway signaling. Treatment with setmelanotide, an MC4R agonist, resulted in weight loss and hunger reduction at 16 weeks in a Phase 2 trial of patients with HO. Here, we report changes in age-appropriate weight-related parameters after 6 months of treatment with setmelanotide in patients with HO who entered a long-term extension (LTE) trial. Methods: A Phase 2, multicenter, open-label study (NCT04725240) examined the efficacy and safety of 16-week setmelanotide treatment in patients aged ≥6 to ≤40 years with a clinical diagnosis of HO. Patients who met the primary endpoint of ≥5% body mass index (BMI) reduction from baseline at Week 16 or experienced investigator-determined clinically meaningful benefit and demonstrated adequate safety were eligible to enroll in the LTE trial (NCT03651765). We assessed the proportion of patients who achieved ≥10% BMI reduction as well as changes in age-appropriate weight-related parameters (ie, mean percent change in body weight for adults [aged ≥18 years] and mean change in BMI Z score and percent of the 95th BMI percentile [%BMI95] for children [aged &amp;lt;18 years]) from index trial baseline to Month 6 of setmelanotide treatment. Results: Of 18 patients originally enrolled in the index trial, 14 (77.8%) continued into the LTE and 13 (72.2%) had received ≥6 months of setmelanotide treatment at the time of this analysis. HO was diagnosed in these patients secondary to treatment of craniopharyngioma (n=11), hypothalamic hamartoma (n=1), and juvenile pilocytic astrocytoma (n=1). At Month 6, 11 of 13 patients (84.6% [90% confidence interval, 59.0%–97.2%) achieved ≥10% BMI reduction from index trial baseline; the remaining 2 patients achieved ≥5% reduction from baseline at Month 6. In adults (n=2), the mean (standard deviation [SD]) percent change in body weight from baseline to Month 6 was −16.2% (7.2%). In children (n=11), the mean (SD) change from baseline in BMI Z score was −1.7 (1.1) and in %BMI95 was −34.8 (14.9) percentage points at Month 6. The most frequent adverse events were nausea (n=9 [69.2%]), skin hyperpigmentation (n=5 [38.5%]), and vomiting (n=4 [30.8%]). Four serious adverse events were reported in 2 patients (Clostridium difficile colitis in 1 patient; malaise, septic shock, and influenza in 1 patient) and were determined not related or unlikely related to study drug. Conclusions: In a heterogeneous population of patients with HO secondary to treatment of hypothalamic tumors, 6 months of setmelanotide treatment was associated with sustained meaningful improvements in weight and BMI with no new safety signals. Presentation: Saturday, June 17, 2023

Adalimumab serum levels and anti-drug antibodies: associations to treatment response and drug survival in inflammatory joint diseases.

To explore associations between serum adalimumab level, treatment response and drug survival in order to identify therapeutic drug levels for therapeutic drug monitoring of adalimumab. Also, to assess occurrence and risk factors of anti-drug antibody (ADAb) formation. Non-trough adalimumab and ADAb levels were measured by automated fluorescence assays in serum collected after 3 months of adalimumab treatment in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) included in the observational NOR-DMARD study. Treatment response was evaluated after 3 months, and drug survival during long-term follow-up. In 340 patients (97 RA, 69 PsA, 174 axSpA), median adalimumab level was 7.3 mg/l (IQR 4.0-10.3). 33 (10%) patients developed ADAb. Findings were comparable across diagnoses. In RA and PsA, adalimumab levels ≥6.0 mg/l were associated with treatment response (Odds Ratio [OR] 2.2 [95% CI 1.0, 4.4]) and improved drug survival (Hazard Ratio [HR] 0.49 [0.27, 0.80]). In axSpA, a therapeutic level could not be identified, but higher adalimumab levels were associated with response. Factors associated with ADAb formation were previous bDMARD use, no methotrexate comedication and use of adalimumab originator compared with GP2017. Higher adalimumab levels were associated with better response and improved drug survival for all diagnoses, with a suggested lower threshold of 6.0 mg/l for RA/PsA. This finding, the large variability in drug levels among patients receiving standard adalimumab dose, and the high proportion of patients developing ADAb, encourages further investigations into the potential role of therapeutic drug monitoring of adalimumab.

Real-World Hemoglobin A1c Changes, Prescribing Provider Types, and Medication Dose Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

Given the lack of real-world data on oral semaglutide use outside clinical trials, the purpose of this study was to describe dose, prescriber specialty, and change in hemoglobin A1c (HbA1c) after 6months of oral semaglutide treatment for patients with type 2 diabetes mellitus (T2DM). This was a retrospective study among adult patients with T2DM with ≥ 1 claim for oral semaglutide between November 1, 2019`1-June 30, 2020. Patients had continuous health plan enrollment ≥ 12months prior to (pre-index) and ≥ 6months following (post-index) the date of the first oral semaglutide claim (index). Dose at initiation and specialty of the prescribing provider were captured. Change in HbA1c between the last post- and pre-index HbA1c measurement was calculated. Patients were stratified by pre-index HbA1c ≥ 9% (poorly controlled) and HbA1c < 9%. A total of 744 HbA1c < 9% and 268 poorly controlled patients were included in the study. Most patients had an initial oral semaglutide dose of 7mg (49.3%) or 3mg (42.9%), prescribed most frequently by a primary care provider (27.8%). Mean HbA1c reduction was 0.8% (p < 0.001). Patients with poorly controlled T2DM had greater HbA1c reductions than patients with HbA1c < 9% (2.0% versus 0.4%, p < 0.001). Patients persistent with oral semaglutide (≥ 90days continuous treatment) had a mean HbA1c reduction of 0.9% (p < 0.001); persistent patients with poorly controlled T2DM had a mean reduction of 2.5%. Patients with T2DM in this study experienced significant reductions in HbA1c within 6months following initiation of oral semaglutide. Patients with a higher starting HbA1c experienced greater HbA1c reductions. The initial dose of oral semaglutide was higher than prescribing instructions indicated for more than half of the study patients.

Real-World Persistence and Treatment Interval in Patients with Diabetic Macular Edema Treated with Anti-Vascular Endothelial Growth Factors in the USA.

There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6months prior to their first anti-VEGF treatment and for a duration of at least 24months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24months of treatment. Discontinuation rate beyond 24months and its association with treatment intervals at 24months was estimated using the Kaplan-Meier method and Cox proportional hazards models. The overall discontinuation rate among the 1702 eligible patients from 24 to 60months after treatment initiation was 30%. At 60months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95%CI 1.43, 2.82], p < 0.001). Patients with DME on longer anti-VEGF treatment intervals at 24months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals.

#5439 HOME DIALYSIS DOES NOT HAVE THE MONOPOLY ON LOW COST

Abstract Background and Aims End-stage kidney disease (ESKD) is a major challenge for health-care systems around the world because of its ever-rising rates and the ensuing rise in health-care costs. The objective of this study was to compare the cost of four dialysis modalities that enable patients to play a substantial role in their own care and have social and professional lives. Method We identified all patients in the national French ESKD REIN registry aged 18–65 years who received any dialysis treatment in 2015-2019, used stepwise indirect linkage with the national health database to analyse exhaustive hospital stays and outpatient health-care utilisation. Four treatment groups were defined: non-assisted haemodialysis in self-care units (scHD), non-assisted automated peritoneal dialysis (naAPD), daily home HD (dhHD), and non-hospital-based nocturnal extended hours HD (neHD).Total costs by categories and subcategories were aggregated monthly and by patient. Costs are expressed as their medians and interquartile ranges (Q1-Q3). Results Our study included 1932 patients with 39 966 patient treatment-months. The median monthly cost for one patient was €6154 (IQR €5088 – €7566) and varied from €5700 for naAPD to €7903 € for dhHD. Analysis by cost subcategories showed that the main cost came from dialysis fee payments —60% of the monthly cost. Hospitalization costs came next (11%). The costs of the different subcategories varied between dialysis modalities. During the study period, the hospitalization rate was 33 per 100 months at risk: 14 for inpatient admissions and 19 for day hospitalization. Day hospitalization was more frequent for patients with home treatment. Various compensatory allowances were paid to 49% of the patients. Conclusion Most of the cost difference variability related to payment methods for the different dialysis techniques. Our study shows that different care strategies could be offered to French dialysis patients. Underused techniques such as neHD might usefully be promoted as they do not involve any excess costs, at least compared with dhHD. Real cost analyses are however needed because some reimbursements are not adapted and deserve to be revised upwards.

Olive extract enriched with hydroxytyrosol improves cardiac and vascular function in patients with stable coronary artery disease: a double-blind, placebo-controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Olive Heart Operational Programme Competitiveness, Entrepreneurship and Innovation 2014–2020 (EPAnEK) Aims We investigated the effect of olive extract enriched with hydroxytyrosol, on vascular and myocardial function markers in patients with stable coronary artery disease (SCAD). Methods In a prospective, cross-over, double-blind, placebo-controlled, clinical trial, 30 patients with stable CAD were randomly assigned to an oral supplement containing olive oil extract enriched with hydroxytyrosol (OOHT) or placebo for one month and then were crossed over to the alternate treatment (placebo or OOHT for one more month). We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography d) Pulse Wave Velocity (PWV) e) oxidative/nitrosative stress and inflammatory biomarkers and blood lipids at baseline and after one month treatment. Results Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.81±0.35 vs 1.77±0.40 μm p = 0.04 3.71±2.12 vs 6.51±2.31%, p&amp;lt;0.001;2.37±0.40 vs 2.45±0.41, p = 0.030 and 11.03±1.81 vs 11.78±2.34 m/sec, p = 0.002), while there was no effect after placebo (p&amp;gt;0.05). Compared to baseline, treatment with OOHT reduced malondialdehyde (MDA) a marker of lipid peroxidation (2.10±1.37 vs 1.69±0.83 mmol/lt, p = 0.045), oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p&amp;lt;0.05) in contrast to placebo. There was a parallel improvement of E’ of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p&amp;lt;0.05) but not after placebo. Conclusions Olive extract enriched with hydroxytyrosol improves endothelial and arterial function likely by reducing oxidative and inflammatory burden leading to improved LV diastolic function after one month of treatment in patients with stable CAD.

Reduction of disease activity, corticosteroids use, and healthcare resource utilisation in patients with systemic lupus erythematosus treated with belimumab in clinical practice settings: OBSErve Spain multicentre study

Introduction and objectivesThis OBSErve Spain study, a part of the international OBSErve programme, evaluated belimumab real-world use and effectiveness following 6 months of treatment in patients with active systemic lupus erythematosus (SLE) in clinical practice in Spain. Materials and methodsIn this retrospective, observational study (GSK Study 200883), eligible patients with SLE receiving intravenous belimumab (10mg/kg) had their disease activity (physician assessed), SELENA-SLEDAI scores, corticosteroid use, and healthcare resource utilisation (HCRU), assessed after 6 months of treatment versus index (belimumab initiation) or 6 months pre-index. ResultsOverall, 64 patients initiated belimumab, mainly due to ineffectiveness of previous treatments (78.1%) and to reduce corticosteroid use (57.8%). Following 6 months of treatment, 73.4% of patients achieved ≥20% overall clinical improvement, while only 3.1% of patients worsened. Mean (standard deviation, SD) SELENA-SLEDAI score decreased from 10.1 (6.2) at index to 4.5 (3.7) 6 months post-index. HCRU decreased from 6 months pre-index to 6 months post-index, with fewer hospitalisations (10.9% vs 4.7% patients) and ER visits (23.4% vs 9.4% patients). Mean (SD) corticosteroid dose decreased from 14.5 (12.5)mg/day at index to 6.4 (5.1)mg/day 6 months post-index. ConclusionsPatients with SLE receiving belimumab for 6 months in real-world clinical practice in Spain experienced clinical improvements and a reduction in HCRU and corticosteroid dose.

P98 Real-world effectiveness of guselkumab in absolute Psoriasis Area and Severity Index-stratified patients with psoriasis: data from the British Association of Dermatologists Biologics and Immunomodulators Register

Abstract Guselkumab is a fully human monoclonal antibody that inhibits interleukin-23 by selectively targeting the p19 subunit. Long-term evaluations have demonstrated high levels of clinical response and improvement in patient-reported outcomes over 5 years of guselkumab treatment in patients with psoriasis. Psoriasis has a significant and negative impact on a patient’s quality of life, even among patients with a Psoriasis Area and Severity Index (PASI) score &amp;lt; 10. Both absolute PASI (aPASI) and the Dermatology Life Quality Index (DLQI) are widely used tools to assess disease impact, as well as treatment eligibility and response. This retrospective analysis evaluated the impact of guselkumab treatment over 1 year across aPASI-stratified patients with psoriasis in BADBIR, a national pharmacovigilance registry documenting longitudinal clinical data for individuals with psoriasis initiating systemic therapies. Retrospective analyses of the guselkumab cohort were carried out using BADBIR data collected up to September 2021. Data were analysed for patients who had initiated guselkumab treatment and had recorded aPASI and DLQI assessments at both baseline and the 12-month follow-up. Patients were stratified according to psoriasis severity at baseline: aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 disease. Treatment effect was defined as the mean improvement in DLQI and aPASI scores for the overall group of guselkumab-treated patients and for subsets of patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline. Five patients were excluded owing to treatment cessation prior to the 12-month cutoff. Following 12 months of guselkumab treatment, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) DLQI score of 2.18 (5.64), 2.79 (5.15) and 1.80 (3.56), representing a decrease of 62.0%, 74.8% and 89.1% from baseline, respectively. Additionally, patients with aPASI &amp;lt; 5, aPASI ≥ 5 to ≤ 10 and aPASI &amp;gt; 10 at baseline achieved a mean (SD) aPASI score of 0.96 (1.84), 3.16 (3.90) and 2.78 (4.93), representing a decrease of 40%, 58.6% and 84.5% from baseline, respectively. Among patients with an aPASI score &amp;lt; 10 at baseline (n = 53), 83.0% (n = 44) achieved aPASI score ≤ 3; of these, 67.9% (n = 36) achieved an aPASI score ≤ 2 and 54.7% (n = 29) achieved an aPASI score ≤ 1. These data demonstrate that guselkumab produces an effective and consistent response in patients with a broad range of disease severity at baseline, as reflected by mean improvements in aPASI and DLQI. Greater reductions in DLQI and aPASI scores were observed after 12 months of guselkumab treatment in patients with more severe psoriasis at baseline.

Evaluation of microRNA expression levels during the craving period of patients diagnosed with severe alcohol use disorder

ABSTRACT Background The aim of this study is to compare the serum MicroRNA (miRNA) expression levels on the first day of hospitalization and at the end of the first month of treatment in patients with alcohol use disorder and severe craving symptoms. Through the obtained data, biological agents targeting microRNA for alcohol craving may be developed. Methods The volunteer group consists of four patients diagnosed with severe alcohol use disorder. Sociodemographic and Clinical Information Form, DSM-5 Structured Clinical Interview-Clinical Version (SCID-5-CV), Penn Alcohol Craving Scale (PACS) were used as clinical assessment tools. Peripheral blood samples were obtained at the time of application and on the 30th day. miRNA isolation was performed. The expression levels of 2578 different mature human miRNAs were measured. Results The miRNAs showing statistically significant differences in peripheral blood samples taken on the 1st and 30th days from alcohol users are as follows: miR-19a-3p, miR-6849-5p, miR-6726-5p, miR-6848-5p, miR-186-5p, miR-6889-5p, miR-933, miR-370-3p, miR-5739, miR-103a-2-5p, miR-6860, miR-1254, miR-1260a, miR-3921, miR-127-3p, miR-8064, miR-6870-5p, miR-4688 Conclusions A significant difference was found between the 1st and 30th days in 18 of 2578 miRNAs scanned. It is aimed to investigate these 18 miRNAs in larger sample groups during the alcohol craving period.