Similar Rates Of Adverse Events Research Articles

Safety and efficacy of intravascular therapy in patients with progressive stroke caused by intracranial large vascular occlusion exceeding the time window of 24 hours

ABSTRACT Purpose To compare endovascular and drug therapies for efficacy and safety in patients with a progressive stroke caused by intracranial large vascular occlusion exceeding the time window of 24 hours. Patients and methods A total of 58 patients with progressive stroke caused by large intracranial vascular occlusion exceeding the time window of 24 hours treated in the stroke center of our hospital for three years were retrospectively analyzed . According to the applied therapy, 58 patients were divided into the endovascular (n = 19) and drug (n = 39) therapy groups. Then, modified Rankin scale (mRS) scores, symptomatic intracranial hemorrhage rates, mortality rates and adverse events were assessed in both groups within 90 days. Results The 90-day good prognosis rate was significantly higher in the endovascular therapy group compared with the drug group (68.4% VS 38.5%, odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.09–0.92; P = 0.032). The 90-day NIHSS scores were lower in the endovascular therapy group compared with the drug group (3.3 ± 2.6 VS 5.2 ± 3.0, OR = −1.89; 95%CI, −3.50 to −0.27; P = 0.023). Meanwhile, the proportion of patients with a Barthel index of 90–100 was significantly higher in the endovascular therapy group compared with the drug group (53.0% VS 25.6%, OR = 0.31; 95%CI, 0.10–0.98; P = 0.042). Finally, both groups showed similar rates of adverse events. Conclusion In patients with progressive stroke caused by large intracranial vascular occlusion exceeding 24 hours, endovascular therapy probably results in improved efficacy at 90 days compared with drug therapy, without increasing the rates of adverse effects.

740-P: Proposed Biosimilar Gan & Lee Insulin Glargine (GL-GLA) Shows Pharmacokinetic (PK) and Pharmacodynamic (PD) Bioequivalence (BE) to U.S.- and EU-Licensed Insulin Glargine (IG)

This randomized, double-blind, three-way crossover trial (NCT04236895) compared the PK and PD properties of GL-GLA, a proposed biosimilar IG by Gan & Lee, US- and EU-licensed Lantus® (US-IG and EU-IG) in 114 male subjects with type 1 diabetes (mean±SD age 42±8 years, BMI 25.8±2.0 kg/m²). Each subject received a single 0.5 U/kg dose of either GL-GLA, EU-IG, or US-IG in each of the 3 euglycemic glucose clamp periods (ClampArt, clamp level 100 mg/dl, clamp duration 30h post-dose). PK is presented as concentrations of the mainly absorbed IG metabolite M1. GL-GLA and comparator insulins showed superimposable profiles for PK and glucose infusion rates (GIR, Figure). PK BE was demonstrated between GL-GLA and the comparator insulins as the point estimates for measured metabolite M1 were close to 100% and 90% CIs were well contained within the pre-defined similarity margins of 80-125% (Figure). Likewise, the primary PD endpoints met BE-criteria as did secondary PK/PD-endpoints including AUCM1.0-12h, AUCM1.12-24h, AUCGIR.0-12h, and AUCGIR.12‑24h. All insulins were well tolerated with similar adverse event rates (19% [GL-GLA]; 26% [US-IG]; 21% [EU-IG]) and only few events of injection site reactions per insulin. In conclusion, GL-GLA demonstrated both PK- and PD-bioequivalence to US- and EU-licensed insulin glargine formulations. Disclosure T. Heise: Advisory Panel; Self; Novo Nordisk A/S, Valbiotis, Research Support; Self; ADOCIA, Afon Technology Ltd., AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan N. V., Nestle, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker’s Bureau; Self; Novo Nordisk A/S. L. Plum-moerschel: None. G. Andersen: None. J. Lu: Employee; Self; Gan & Lee Pharmaceuticals. M. G. Wilson: Consultant; Self; Gan & Lee Pharmaceuticals, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. E. Zijlstra: Speaker’s Bureau; Self; Novo Nordisk A/S. Funding Gan & Lee Pharmaceuticals

Most Appropriate Conventional Disease-Modifying Antirheumatic Drug to Combine With Different Advanced Therapies in Rheumatoid Arthritis: A Systematic Literature Review With Meta-Analysis.

In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies. We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated. The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I2 = 28%), with a lower retention rate at 12months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I2 = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed. The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

Per Oral Pyloromyotomy for Treatment of Gastroparesis in a Pediatric Patient

Efficacy of ARB/HCTZ Combination Therapy in Uncontrolled Hypertensive Patients Compared with ARB Monotherapy: A Meta-Analysis.

Objective To evaluate the efficacy of combination of angiotensin receptor blocker (ARB) with hydrochlorothiazide (HCTZ) compared to ARB alone in patients with uncontrolled hypertension via a systematic review and meta-analysis. Methods We searched databases till July 2019 using relevant search terms. We included articles that were randomised controlled trials (RCTs) comparing ARB/HCTZ with ARB for a duration of at least 4 weeks and reported on the efficacy or safety. Meta-analyses for efficacy outcomes were performed. In addition, groups given different concentrations of HCTZ (12.5 and 25 mg) were analysed separately. Results Sixteen RCTs (12,055 participants) were included. Overall, ARB/HCTZ combination therapy (both 12.5 and 25 mg HCTZ combination) resulted in better sitting systolic and diastolic blood pressure control than ARB alone (mean difference (95% confidence interval (CI): −5.69 [−6.66, −4.73] for 12.5 mg and −9.10 [−11.78, −6.42] for 25 mg and mean difference (95% CI): −2.91 [−3.31, −2.51] for 12.5 mg and −4.16 [−4.75, −3.58] for 25 mg). ARB/HCTZ combination therapy resulted in a higher rate of target blood pressure achievement compared to ARB alone (risk ratio (95% CI): 1.50 [1.42, 1.59]). ARB/HCTZ combination therapy had similar rates of total adverse events (AEs) and severe AEs compared to ARB alone. Conclusion ARB/HCTZ combination therapy is more efficacious for controlling blood pressure, and combination with a low concentration of HCTZ has similar AEs compared to ARB alone. Clinicians should consider adding HCTZ in the medication regime of patients with uncontrolled hypertension using ARB, if their clinical profile allows.

Advanced therapies in inflammatory bowel disease: Special considerations.

Advanced therapies in inflammatory bowel disease: Special considerations.

Yttrium-90 Microspheres for Intermediate- or Advanced-Stage Hepatocellular Carcinoma


 Transarterial radioembolization using yttrium-90 (90Y) microspheres is a therapeutic option for patients with intermediate- or advanced-stage hepatocellular carcinoma, including those with recurrent or inoperable hepatocellular carcinoma.
 Overall, the evidence suggests that patients treated with 90Y-based transarterial radioembolization may experience no difference in overall survival, progression-free survival, and tumour response when compared to patients who received transarterial chemoembolization therapies or systemic treatment with sorafenib or lenvatinib.
 Patients treated with transarterial radioembolization generally experienced similar rates of adverse events compared to those treated with transarterial chemoembolization, although there were some instances where treatment with transarterial radioembolization led to increased or decreased risks of specific adverse events. The comparative safety of transarterial radioembolization versus systemic treatment with sorafenib was unclear as the included studies did not statistically compare the risks of experiencing adverse events.
 Evidence regarding the cost-effectiveness of 90Y microspheres for treating hepatocellular carcinoma is conflicting. Three economic evaluations suggest treatment with transarterial radioembolization is likely to be cost-effective or dominant — less costly and more effective — compared to transarterial chemoembolization or systemic therapies, while a single economic study suggested treatment with sorafenib or lenvatinib is most likely to be cost-effective or dominant compared to transarterial radioembolization.

EVO100 prevents chlamydia and gonorrhea in women at high risk of infection

According to the Centers for Disease Control and Prevention, rates of infection for Chlamydia trachomatis and Neisseria gonorrhoeae are increasing in the United States. EVO100 is an investigational antimicrobial, pH-modulating, vaginal gel with active ingredients L-lactic acid, citric acid, and potassium bitartrate that is being evaluated for the prevention of sexually transmitted infections. The objective of this phase 2B/3 study was to assess the efficacy and safety of EVO100 for the prevention of chlamydia and gonorrhea. AMPREVENCE was a double-blinded, placebo-controlled, multicenter study based in the United States conducted over approximately 16 weeks in women at the age of 18 to 45 years who were at risk of urogenital chlamydia and gonorrhea infection. Enrolled women had been diagnosed as having and treated for chlamydia or gonorrhea ≤16 weeks before enrollment. Women received either EVO100 or placebo vaginal gel and were instructed to apply the study drug immediately before or up to 1 hour before each act of vaginal sexual intercourse. The primary and secondary endpoints were the prevention of urogenital chlamydia and gonorrhea, respectively. Exploratory outcomes include women's overall satisfaction with EVO100. In total, 860 women were randomized 1:1 to receive EVO100 (n=426) or placebo (n=434), and 764 women (EVO100, n=376; placebo, n=388) were documented as using the study drug at least once. Baseline characteristics were similar between treatment arms. Overall, women had a mean age of 27.7 years (standard deviation, 6.9) and body mass index of 28.9 kg/m2 (standard deviation, 8.0). Most women were of White (54.3% [467 of 860]) or African American (41.6% [358 of 860]) race and of non-Hispanic/Latina ethnicity (67.1% [577 of 860]). The chlamydia infection rate in EVO100 users was 4.8% (14 of 289) compared with 9.7% (28 of 290) among placebo users (P=.0256), representing a relative risk reduction of 50%. For gonorrhea, the infection rate was 0.7% (2 of 280) in the EVO100 arm compared with 3.2% (9 of 277) in the placebo arm (P=.0316), representing a relative risk reduction of 78%. Increased efficacy was observed with increased adherence, and chlamydia infection rates were significantly reduced with increased adherence in the EVO100 group compared with placebo. Across both arms, there were similar rates of all-cause adverse events (EVO100, 21.3% [80 of 376]; placebo, 20.4% [79 of 388]) and treatment-related adverse events (EVO100, 7.2% [27 of 376]; placebo, 7.5% [29 of 388]). The most common adverse events in the EVO100 arm were vulvovaginal candidiasis (5.1% [19 of 376]), vaginal discharge (3.2% [12 of 376]), and urinary tract infection (3.2% [12 of 376]) and, in the placebo arm, bacterial vaginosis (4.6% [18 of 388]), urinary tract infection (2.6% [10 of 388]), and vaginal discharge (2.6% [10 of 388]). Few women discontinued owing to adverse events in either arm (EVO100, 1.1% [4 of 376]; placebo, 1.5% [6 of 388]). No treatment-related serious adverse events were reported. Most EVO100 users (88%) were satisfied or very satisfied with EVO100 after 16 weeks of use. EVO100 significantly reduced the risk of chlamydia and gonorrhea infections in women at high risk of Chlamydia trachomatis and Neisseria gonorrhoeae infection and was well tolerated, with observed adverse events consistent with its known safety profile.

BMI and atrial fibrillation recurrence post catheter ablation: A dose-response meta-analysis.

The evidence on the association between obesity and atrial fibrillation (AF) recurrence was equivocal. We aimed to evaluate the dose-response relationship between body mass index (BMI) and AF recurrence and adverse events. A systematic literature search was conducted using PubMed, Europe PMC, EBSCO, ProQuest and Cochrane Library. Obesity was defined as BMI ≥28kg/m2 . The primary outcome was AF recurrence, and the secondary outcome was adverse events. Adverse events were defined as procedure-related complications and cardio-cerebrovascular events. There were a total of 52,771 patients from 20 studies. Obesity was associated with higher AF recurrence (Odds ratio [OR] 1.30 [95% confidence interval [CI] 1.16-1.47], P<.001; I2 : 72.7%) and similar rate of adverse events (OR 1.21 [95% CI 0.87-1.67], P=.264; I2 : 23.9%). Meta-regression showed that the association varies by age (coefficient: -0.03, P=.024). Meta-analysis of highest versus lowest BMI showed that the highest group had higher AF recurrence (OR 1.37 [95% CI 1.18-1.58], P<.001; I2 : 64.9%) and adverse events (OR 2.02 [95% CI 1.08-3.76], P=.028; I2 : 49.5%). The linear association analysis for AF recurrence was not significant (P=.544). The dose-response relationship for BMI and AF recurrence was nonlinear (pnonlinearity <0.001), the curve became steeper at 30-35kg/m2 . For adverse events, an increase of 1% for every 1kg/m2 increase in BMI (OR 1.01 [95% CI 1.00-1.02], P=.001), the relationship was nonlinear (pnonlinearity =0.001). Obesity was associated with higher AF recurrence in patients undergoing catheter ablation. High BMI might be associated with a higher risk for adverse events. CRD42020198787.

Access-site hematoma in distal and conventional transradial access: a randomized trial.

Distal transradial access (dTRA) has been recently proposed as an innovative access for coronary procedures and a valuable alternative to conventional transradial access (cTRA). The aim of this study was to assess the safety of dTRA versus cTRA in patients undergoing percutaneous coronary angiography and intervention. In this single-center randomized trial, consecutive patients admitted for stable cardiac condition or acute coronary syndrome (ACS) were assigned to dTRA or cTRA. The primary endpoint was an early discharge after transradial stenting of coronary arteries (EASY) grade ≥II access-site hematoma (ASH). Vascular access failure, radial artery occlusion (RAO) at hospital discharge, 30-day rates of death, myocardial infarction, stroke and bleeding not related to coronary artery bypass grafting were considered as secondary endpoints. A total of 204 patients were included and randomized to dTRA (N.=100) or cTRA (N.=104). The two populations were similar, except for a higher percentage of ACS in the dTRA than in the cTRA group (38% versus 24%, P=0.022). The rate of EASY grade ≥II ASH was lower in dTRA than in cTRA patients, but the difference was not statistically significant (4% versus 8.4%, respectively, P=0.25). Vascular access failure was more frequent in dTRA patients than in cTRA patients (34% versus 8.7%, P<0.0001). We detected no case of RAO at hospital discharge and similar rates of 30-day adverse events in both groups. DTRA is safe and feasible. When compared to cTRA, dTRA is technically more demanding and limited by more frequent crossover to an alternative vascular access.

A 2-year investigation of the impact of the computed tomography-derived fractional flow reserve calculated using a deep learning algorithm on routine decision-making for coronary artery disease management.

This study aims to investigate the safety and feasibility of using a deep learning algorithm to calculate computed tomography angiography-based fractional flow reserve (DL-FFRCT) as an alternative to invasive coronary angiography (ICA) in the selection of patients for coronary intervention. Patients (N = 296) with symptomatic coronary artery disease identified by coronary computed tomography angiography (CTA) with stenosis over 50% were retrospectively enrolled from a single centre in this study. ICA-guided interventions were performed in patients at admission, and DL-FFRCT was conducted retrospectively. The influences on decision-making by using DL-FFRCT and the clinical outcome were compared to those of ICA-guided care for symptomatic CAD at the 2-year follow-up evaluation. Two hundred forty-three patients were evaluated. Up to 72% of diagnostic ICA studies could have been avoided by using a DL-FFRCT value > 0.8 as a cut-off for intervention. A similar major adverse cardiovascular event (MACE) rate was observed in patients who underwent revascularisation with a DL-FFRCT value ≤ 0.8 (2.9%) compared to that of ICA-guided interventions (3.3%) (stented lesions with ICA stenosis > 75%) (p = 0.838). DL-FFRCT can reduce the need for diagnostic coronary angiography when identifying patients suitable for coronary intervention. A low MACE rate was found in a 2-year follow-up investigation. • Seventy-two percent of diagnostic ICA studies could have been avoided by using a DL-FFRCT value > 0.8 as a cut-off for intervention. • Coronary artery stenting based on the diagnosis by using a 320-detector row CT scanner and a positive DL-FFRCT value could potentially be associated with a lower occurrence rate of major adverse cardiovascular events (2.9%) within the first 2 years. • A low event rate was found when intervention was performed in tandem lesions with haemodynamic significance based on DL-FFRCT < 0.8 as a cut-off value.

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200mg once daily, esomeprazole 20mg + amoxicillin 1000mg twice daily) for 14days, or LEA group (levofloxacin 500mg once daily, esomeprazole 20mg + amoxicillin 1000mg twice daily) for 14days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1month after discontinuation. A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

Tolerability of eptinezumab in overweight, obese or type 1 diabetes patients.

IntroductionIn addition to its role in the pathogenesis of migraine, calcitonin gene‐related peptide (CGRP) is implicated in the regulation of insulin secretion. However, there are limited data on the use of CGRP inhibitor monoclonal antibodies in individuals who are overweight/obese and those with diabetes.MethodsTwo randomized, double‐blind, placebo‐controlled trials were conducted to assess the safety and metabolic effects of eptinezumab in non‐migraine overweight/obese patients (study 1) and patients with type 1 diabetes (T1D; study 2). The primary end‐point in overweight/obese patients was safety and changes in basal metabolic rate (BMR), defined as the energy expenditure during the fasting and resting states. In patients with T1D, the primary end‐points were safety and insulin sensitivity as assessed by the bodyweight and insulin concentration corrected glucose infusion rate (M/I).ResultsA total of 24 patients were enrolled in study 1, and 21 patients were enrolled in study 2. In overweight/obese patients, there was no significant difference in the least squares (LS) mean change in BMR between the eptinezumab‐ and placebo‐treated patients from baseline to day 7 (6.4 vs −25.2 Kcal/day; LS mean difference 31.6 [95% confidence interval −90.6, 153.8]). In patients with T1D, there was no significant difference in insulin sensitivity between the eptinezumab and placebo groups. Eptinezumab was well tolerated in both studies with a similar rate of adverse events between treatment groups, and no new safety signals were identified.ConclusionEptinezumab was well tolerated and not associated with adverse metabolic effects in patients who were overweight/obese or had T1D, providing ongoing support for the use of eptinezumab in these subgroups of patients with migraine.

Outcomes of uninterrupted vs interrupted Periprocedural direct oral Anticoagulants in atrial Fibrillation ablation: A meta-analysis.

BackgroundStudies indicate that uninterrupted anticoagulation (UA) is superior to interrupted anticoagulation (IA) in the periprocedural period during catheter ablation of atrial fibrillation. Still IA is followed in many centers considering the bleeding risk. This meta‐analysis compares interrupted and uninterrupted direct oral anticoagulation during catheter ablation of atrial fibrillation.MethodsA systematic search into PubMed, EMBASE, and the Cochrane databases was performed and five studies were selected that directly compared IA vs UA before ablation and reported procedural outcomes, embolic, and bleeding events. The primary outcome of the study was major adverse cerebro‐cardiovascular events.ResultsThe meta‐analysis included 840 patients with UA and 938 patients with IA. Median follow‐up was 30 days. Activated clotting time (ACT) before first heparin bolus was significantly longer with UA (P = .006), whereas mean ACT was similar between the two groups (P = .19). Total heparin dose needed was significantly higher with IA (mean, ‒1.61; 95% CI, ‒2.67 to ‒0.55; P = .003). Mean procedure time did not vary between groups (P = .81). Overall complication rates were low, with similar major adverse cerebro‐cardiovascular event (P = .40) and total bleeding (P = .55) rates between groups. Silent cerebral events (SCEs) were significantly more frequent with IA (log odds ratio, ‒0.90; 95% CI, ‒1.59 to ‒0.22; P < .01; I 2, 33%). Rates of major bleeding, minor bleeding, pericardial effusion, cardiac tamponade, and puncture complications were similar between groups.ConclusionsUA during atrial fibrillation ablation has similar bleeding event rates, procedural times, and mean ACTs as IA, with fewer SCEs.

Phase I Trial of DNA Methyltransferase Inhibitor Guadecitabine Combined with Cisplatin and Gemcitabine for Solid Malignancies Including Urothelial Carcinoma (SPIRE)

Abstract Purpose: Preclinical data indicate that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers. Patient and Methods: SPIRE comprised a dose-escalation phase for incurable metastatic solid cancers, followed by a randomized dose expansion phase for neoadjuvant treatment of T2–4a N0 M0 bladder urothelial carcinoma. The primary objective was a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin. Treatment comprised 21-day gemcitabine and cisplatin cycles (cisplatin 70 mg/m2, i.v., day 8 and gemcitabine 1,000 mg/m2, i.v., days 8 + 15). Guadecitabine was injected subcutaneously on days 1–5, within escalation phase cohorts, and to half of 20 patients in the expansion phase. Registration ID: ISRCTN 16332228. Results: Within the escalation phase, dose-limiting toxicities related predominantly to myelosuppression requiring G-CSF prophylaxis from cohort 2 (guadecitabine 20 mg/m2, days 1–5). The most common grade ≥3 adverse events in 17 patients in the dose-escalation phase were neutropenia (76.5%), thrombocytopenia (64.7%), leukopenia (29.4%), and anemia (29.4%). Addition of guadecitabine to gemcitabine and cisplatin in the expansion phase resulted in similar rates of severe hematologic adverse events, similar cisplatin dose intensity, but modestly reduced gemcitabine dose intensity. Radical treatment options after chemotherapy were not compromised. Pharmacodynamics evaluations indicated guadecitabine maximal target effect at the point of cisplatin administration. Pharmacokinetics were consistent with prior data. No treatment-related deaths occurred. Conclusions: The guadecitabine RP2D was 20 mg/m2, days 1–5, in combination with gemcitabine and cisplatin and required GCSF prophylaxis. Gene promoter methylation pharmacodynamics are optimal with this schedule. Addition of guadecitabine to gemcitabine and cisplatin was tolerable, despite some additional myelosuppression, and warrants further investigation to assess efficacy.

Comparison of Three Methods of Gallbladder Drainage for Patients with Acute Cholecystitis Who Are at High Surgical Risk: A Network Meta-Analysis and Systematic Review.

Background: Percutaneous gallbladder drainage (PTGBD), endoscopic ultrasound-guided gallbladder drainage (EUSGBD), and endoscopic transpapillary gallbladder drainage (ETGBD) are used for the treatment of patients with acute cholecystitis who are at high surgical risk. However, it is unclear which procedure is associated with the best outcomes. Methods: We systematically searched records in PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov up to March 1, 2020. Studies that compared at least two of PTGBD, ETGBD, and EUSGBD were included. Results: A total of 13 studies were included in the present analyses. PTGBD, EUSGBD, and ETGBD were associated with similar clinical success, adverse event, recurrent cholecystitis, reintervention, and mortality rates. PTGBD was associated with a higher technical success rate than EUSGBD (odds ratio [OR] = 0.75, 95% confidence interval [CI] = 0.40-1.41) or ETGBD (OR = 0.73, 95% CI = 0.35-1.53). EUSGBD was associated with the highest probability of clinical success (67.5%), and the lowest prevalences of adverse events (57.0%) and recurrent cholecystitis (60.9%). ETGBD was associated with the best reintervention outcomes (81.8%). Conclusions: Compared with PTGBD and ETGBD, EUSGBD appears to be preferable with respect to both safety and efficacy for the treatment of patients with acute cholecystitis who are at high surgical risk.

Secukinumab real world drug retention compared to TNF-alpha inhibitors in psoriatic arthritis.

To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases. PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves. Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi. This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.

1690. Oral Fosfomycin for the Treatment of Bacterial Prostatitis

BackgroundBacterial prostatitis (BP) is notoriously difficult to treat. Few antibiotics penetrate the prostate well, and antibiotic resistance can further restrict options. A small body of recent literature suggests fosfomycin, a bactericidal antibiotic that can treat multidrug resistant (MDR) organisms and has little cross-resistance, may both effectively penetrate the prostate and treat BP. This study sought to add to the limited literature on the efficacy and safety of fosfomycin for BP.MethodsPatients treated for BP with fosfomycin between November 2009 and May 2019 at the San Diego VAMC were retrospectively examined. Patients were excluded if they died within 6 months of completion of fosfomycin or if fosfomycin was used for less than half of the treatment course. If fosfomycin was used to treat a urinary tract infection (UTI), an infectious disease physician determined if the UTI may have been undiagnosed BP. Outcomes were clinical and microbiological cure at 6 months and adverse events to fosfomycin reported during the trial period.ResultsThe study included 29 patient cases. All but one had chronic BP. Most initially presented outpatient (66%). Almost all had prior occurrences of BP treated with antibiotics (90%). The most common pathogen was E. coli (73%), and 87% of all pathogens were MDR. The most common fosfomycin dosing regimen was 3g PO q48h (66%), with 3g PO q24h as the next most common (21%). Less than half of patient cases received fosfomycin courses > 28 days (38%), while the remaining received courses < 14 days (62%). At 6 months, 48% achieved clinical cure and 44% achieved microbiological cure. When comparing those who received courses > 28 days vs. courses < 14 days, clinical cure was achieved in 55% vs. 44% and microbiological cure in 56% vs. 39%, respectively. Adverse events were reported in 6 unique patients (27%), mostly diarrhea with one instance of nausea.ConclusionFosfomycin may be a safe and effective alternative for the treatment of chronic BP. Treatment courses longer than 4 weeks may be more effective than courses shorter than 2 weeks with a similar rate of adverse events. This study also highlights inpatients as a relevant BP population and a need for provider education on identifying BP and prescribing optimal durations of therapy.Disclosures All Authors: No reported disclosures

Current Issues of Empirical Therapy of Severe Bacterial Community-Acquired Pneumonia During the Season of Respiratory Viral Infections

Progredient growth of morbidity and mortality of patients with community-acquired pneumonia (CAP) requires optimization of treatment including antibacterial therapy. Implementation of molecular-genetic methods of diagnostics of viral and viral-bacterial infections in clinical practice has significantly augmented the conception of etiology of community-acquired pneumonia. Seasonal fluctuation of CAP prevalence corresponds with growth of morbidity of acute respiratory infections and influenza which contribute to the etiological structure of CAP by increasing the risk of infection caused by staphylococci. The synergy between influenza A virus and S.aureus has been shown; it is associated with an increase of virus replication in the presence of specific staphylococcal proteases and the ability of viruses to increase adhesion of S.aureusin the respiratory tract, to decrease phagocytosis of S.aureus by macrophages/neutrophils and production of antimicrobial peptides, as well as to increase the probability of secondary bacterial co-infection. Therefore, the most important requirement for the empiric therapy agents of CAP is high streptococcal and staphylococcal activity. According to the current guidelines on antimicrobial therapy of severe CAP, antipneumococcic cephalosporins, macrolides, and fluoroquinolones are the basic treatment agents, but none of them have the combined high antistaphylococcal and antipneumococcal activity inherent in ceftaroline. The advantages of ceftaroline over ceftriaxone and levofloxacin in terms of the probability of reaching target concentrations for clinically relevant pharmacokinetic/pharmacodynamic parameters are shown. Meta-analysis of randomized clinical trials showed the higher clinical efficacy of ceftaroline in comparison to ceftriaxone with similar adverse event rate. Summarized analysis of antibiotic susceptibility data, pharmacokinetic/pharmacodynamic and clinical data, as well as negative epidemiological trends confirms the necessity of optimization of antimicrobial therapy of CAP for implementation of ceftaroline advantages against pneumococci and staphylococci in comparison to other β-lactams. Therefore, empiric treatment with ceftaroline is the most rational option for the therapy of CAP in critically ill patients during the season of respiratory viral infection.