Triple Therapy Group Research Articles

In-hospital Bleeding Outcomes of Oral Anticoagulant and Dual Antiplatelet Therapy During Percutaneous Coronary Intervention: An Analysis From the Japanese Nationwide Registry.

The type of periprocedural antithrombotic regimen that is the safest and most effective in percutaneous coronary intervention (PCI) patients on oral anticoagulant (OAC) therapy has not been fully investigated. We aimed to retrospectively investigate the in-hospital bleeding outcomes of patients receiving OAC and antiplatelet therapies during PCI using Japanese nationwide multicenter registry data. A total of 26,938 patients who underwent PCI with OAC and antiplatelet therapies between 2016 and 2017 were included. We investigated in-hospital bleeding requiring blood transfusion, mortality, and stent thrombosis according to the antithrombotic regimens used at the time of PCI: OAC + single antiplatelet therapy (double therapy) and OAC + dual antiplatelet therapy (triple therapy). The antiplatelet agents included aspirin, clopidogrel, and prasugrel. The OAC agents included warfarin and direct OACs. Adjusting the dose of OAC or intermitting OAC before PCI was at each operator's discretion. In the study population [mean age (SD), 73.5 (9.5) years; women, 21.5%], the double therapy and triple therapy groups comprised 5546 (20.6%) and 21,392 (79.4%) patients, respectively. Bleeding requiring transfusion was not significantly different between the groups [adjusted odds ratio (aOR), 0.700; 95% confidence interval (CI), 0.420-1.160; P = 0.165] (triple therapy as a reference). Mortality was not significantly different (aOR, 1.370; 95% CI, 0.790-2.360; P = 0.258). Stent thrombosis was significantly different between the groups (aOR, 3.310; 95% CI, 1.040-10.500; P = 0.042) (triple therapy as a reference). In conclusion, for patients on OAC therapy who underwent PCI, periprocedural triple therapy may be safe with respect to in-hospital bleeding risks. However, further investigations are warranted to establish the safety and efficacy of periprocedural triple therapy.

Initial Triple Oral Therapy in Pulmonary Arterial Hypertension (PAH): Extended Long-Term Outcome Data from TRITON

<h3>Purpose</h3> In TRITON (NCT02558231), initial triple (macitentan, tadalafil, selexipag) and initial double (macitentan, tadalafil, placebo) oral therapy in newly diagnosed PAH patients markedly improved hemodynamic and functional parameters at week 26, with no difference between groups. Main analysis up to end of main observation period suggested that initial triple therapy reduced the risk of disease progression vs initial double therapy. Here, we present data from a longer follow-up period (up to end of study [EOS]). <h3>Methods</h3> In this multicenter, double-blind, randomized, placebo-controlled, phase 3b study, end of the main observation period occurred when the last patient randomized completed week 26. Unblinding occurred after end of main observation period, and patients were further followed-up to EOS, which occurred 30 days after last intake of study treatment. Time to first disease progression event (pre-specified) and all-cause death (post-hoc) were analyzed with Cox regression; all disease progression events were analysed (post-hoc) using a negative binomial model. Events were centrally adjudicated in a blinded fashion. <h3>Results</h3> Median follow-up time at EOS was 100 weeks in the initial triple therapy group (n=123) and 95 weeks in the initial double therapy group (n=124) (Table). The hazard ratio for the risk of a first disease progression event and the rate of all disease progression events for initial triple vs initial double therapy were similar at end of main observation period and at EOS (Table). Four patients in the initial triple and 12 in the initial double therapy groups died before EOS. Safety up to EOS was consistent with findings at end of main observation period. <h3>Conclusion</h3> Results at EOS and at end of main observation period are consistent and suggest a signal for improved long-term outcome with initial triple vs initial double oral therapy.

Efficacy and safety of rivaroxaban and ticagrelor in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention

AimsTo compare the efficacy and safety of a dual therapy (rivaroxaban and ticagrelor) with a triple therapy (aspirin, clopidogrel and warfarin) in Chinese elderly patients with nonvalvular atrial fibrillation (NVAF) undergoing percutaneous coronary intervention (PCI). MethodsA total of 106 elderly Chinese patients with NAVF after PCI were randomly divided into a dual therapy group treated with ticagrelor 90 mg twice daily and rivaroxaban 15 mg once daily after PCI, and a triple therapy group treated with aspirin 100 mg and clopidogrel 75 mg once daily combined with the dose-adjusted vitamin K antagonist warfarin once daily. The mean follow-up time was 1 year. The primary endpoint was the composite death rate from cardiovascular causes, myocardial infarction, stroke or stent thrombosis. The safety endpoint was clinically significant bleeding (a composite value of major, minor and minimal bleeding). ResultsThere were no significant differences between the 2 groups regarding the basic characteristics of the patients. The primary composite endpoint of the dual therapy group after 1 year was not significantly different from the triple therapy group (16.7% vs 15.2%, P = 0.86; HR 1.02; 95% CI: 0.82–1.24), but there was a significant difference in the incidence of hemorrhage (7.4% vs 26.9% P = 0.01; HR 0.71; 95% CI: 0.62–0.83) between the 2 groups. ConclusionsIn elderly Chinese patients with NVAF undergoing PCI, the efficacy of dual (ticagrelor plus rivaroxaban) treatments was comparable to the triple antithrombotic regime (warfarin plus dual antiplatelet therapy). The overall incidence of bleeding was significantly reduced with dual treatment compared to the triple treatment regime.

Safety and efficacy of double vs. triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention： a systematic review and meta-analysis of vitamin k antagonist a

Objective: To compare the safety and efficacy of double therapy (DT) (no aspirin) versus triple therapy (TT) (with aspirin) antithrombotic drugs in patients with atrial fibrillation and acute coronary syndrome or underwent percutaneous coronary intervention (PCI).Methods: We searched PubMed, Cochrane, Scopus, and Web of Science for relevant articles from inception to December 2020. We conducted the analysis of dichotomous outcomes using risk ratio (RR) and relative 95% confidence interval (CI), while the continuous outcomes were analyzed using mean difference (MD) and relative 95% CI. Heterogeneous outcomes were analyzed with random-effects model, and homogeneous data were analyzed with fixed-effects model. We assessed the risk of bias among the included studies by using Cochrane’s risk of bias tool.Results: A total of five studies were included. Regarding Major or Minor Bleeding, the overall risk ratio was significantly lower with DT group compared with TT group (RR=0.60 [0.45, 0.81], (P = 0.07)). For the safety endpoint (TIMI major or minor bleeding, TIMI major bleeding) favored DT group over TT group, respectively (RR=0.60 [0.45, 0.81], (P = 0.07)); (RR= 0.55 [0.43, 0.70], (P &lt; 0.01)). Intracranial hemorrhage did not differ between both groups (RR=0.62 [0.37, 1.05], (P = 0.07)). The efficacy endpoint, all-cause death showed no significant difference between both groups (RR=1.08 [0.89, 1.31], (P = 0.42)). There were no significant differences between two groups in cardiovascular death, stent thrombosis, myocardial infarction and stroke, respectively (RR=1.10 [0.86, 1.41], (P = 0.43); (RR=1.40 [0.92, 2.12], (P = 0.11); (RR=1.20 [0.98, 1.49], (P = 0.08); (RR=0.95 [0.66, 1.37], (P = 0.79).; respectively).Conclusion: Compared with triple antithrombotic therapy, double antithrombotic therapy is associated with lower bleeding risks, including minor and major bleeding, but the incidence of efficacy endpoints was similar between both groups.  Â

Concomitant Therapy versus Triple Therapy: Efficacy in H. Pylori Eradication and Predictors of Treatment Failure.

To compare concomitant therapy (CT) and triple therapy (TRT) for success in helicobacter (H.) pylori eradication and identify factors associated with treatment failure. Quasi-experimental comparative study. Department of Medicine and Gastroenterology, Services Institute of Medical Sciences from December 2018 till July 2019. Patients with H. pylori infection were randomly assigned to receive two weeks of either CT or TRT. H. pylori eradication was confirmed by repeat biopsy four weeks post-treatment. Treatment outcome was compared using Chi-square test, while binary logistic regression identified predictors of treatment failure. Two hundred and eleven patients with H. pylori infection, having mean age 40.15 (±13.04) and male/female ratio 0.9/1 (100/111) after randomisation, were treated with CT in 105 patients (49.8%) and TRT in 106 patients (50.2%). H. pylori was eradicated in 84.3% (150/178) patients with completed follow-up. H. pylori eradication was achieved in 91.9% of CT group as compared to 77.2% in TRT group (p = 0.007, OR 3.38: 95% CI 1.3-8.3). Age ≥40 years (p = 0.02), symptoms duration >6 months (p = 0.001), and prior proton pump inhibitor use for >4 weeks (p = 0.01), were identified as independent predictors of treatment failure. CT achieves better H. pylori eradication than TRT. Older age, longer duration of illness, and previous proton pump inhibitor use were independent predictors of H. pylori treatment failure. Key Words: Concomitant therapy, Eradication, H. pylori, Triple therapy.

A comparative study of efficacy and adverse effects of monotherapy with combination therapy for oral anti-diabetics in diabetes mellitus type 2 patients

Background: Diabetes mellitus type 2 is associated with deteriorating blood sugar levels along with countless metabolic disorders. Treatment strategy plays a crucial role in achieving target blood sugar levels to reduce morbidity and early mortality. Diabetes mellitus type 2 is a chronic, long-term medical condition, in which the body does not produce insulin or is unable to utilize it properly resulting in uncontrolled blood sugar levels. Oral antidiabetic drugs are given as mono and combination therapy to achieve controlled blood sugar levels, based on the clinical conditions of each patient. Aims and Objective: The purpose of our study is to compare the efficacy and adverse effects in monotherapy with that of combination therapy for oral anti-diabetics in diabetes mellitus type 2 patients. Materials and Methods: A prospective cross-sectional study of 11 months period was conducted on 200 patients, in the Department of General Medicine of a Tertiary Care Hospital. Ethics committee permission was obtained from the institutional ethical committee before initiation of the study. Based on the oral anti-diabetic therapy pattern, patients were divided into three groups, Group 1 (Monotherapy), Group 2 (Dual therapy), and Group 3 (Triple therapy). Following inclusion and exclusion criteria, demographic parameters, and oral anti-diabetic therapy patterns were collected and assessed for efficacy and adverse effects. Results: Among 200 patients studied, 50% received monotherapy (Group 1), 30% received dual therapy (Group 2), and 20% received triple therapy (Group 3) treatment. Fasting blood sugar, postprandial blood sugar, and glycosylated hemoglobin levels were monitored. Controlled blood glucose levels were achieved successfully in combination therapy groups and it was found to be more efficacious than monotherapy group. Patients on monotherapy had less adverse effects than combination therapy. Conclusion: Combination therapy was substantial in controlling blood sugar levels compared to monotherapy. Combination therapy is a better treatment choice for diabetes mellitus type 2 patients. Adverse effects were reported fewer in the monotherapy group in comparison with combination therapy groups.

Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT.

To compare the long-term efficacy of initiating therapy with metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes mellitus (T2DM) versus sequential addition of metformin followed by glipizide and insulin. Drug-naive patients (N = 318) with new-onset T2DM were randomly assigned to receive for 3 years either 1) combination therapy with metformin, pioglitazone, and exenatide (triple therapy) or 2) sequential addition of metformin followed by glipizide and insulin (conventional therapy) to maintain HbA1c at <6.5% (48 mmol/mol). Insulin sensitivity and β-cell function were measured at baseline and 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years. Baseline HbA1c ± SEM values were 9.0% ± 0.2% and 8.9% ± 0.2% in the triple therapy and conventional therapy groups, respectively. The decrease in HbA1c resulting from triple therapy was greater at 6 months than that produced by conventional therapy (0.30% [95% CI 0.21-0.39]; P = 0.001), and the HbA1c reduction was maintained at 3 years in patients receiving triple therapy compared with conventional therapy (6.4% ± 0.1% and 6.9% ± 0.1%, respectively), despite intensification of antihyperglycemic therapy in the latter. Thus, the difference in HbA1c between the two treatment groups at 3 years was 0.50% (95% CI 0.39-0.61; P < 0.0001). Triple therapy produced a threefold increase in insulin sensitivity and 30-fold increase in β-cell function. In conventional therapy, insulin sensitivity did not change and β-cell function increased by only 34% (both P < 0.0001 vs. triple therapy). Triple therapy with agents that improve insulin sensitivity and β-cell function in patients with new-onset T2DM produces greater, more durable HbA1c reduction than agents that lower glucose levels without correcting the underlying metabolic defects.

The Skeletal Effects of Short-Term Triple Therapy in a Rat Model of Gastric Ulcer Induced by Helicobacter pylori Infection.

PurposeTriple therapy is the standard therapy to eradicate Helicobacter pylori (H.pylori) infection. Chronic use of proton pump inhibitors (PPIs), a component of triple therapy, is associated with osteoporosis. However, the skeletal effects of short-term triple therapy containing PPI remain elusive. This study aims to determine the skeletal effect of short-term triple therapy in a rat model of gastric ulcer induced by H. pylori.MethodsThree-month-old male Sprague Dawley rats were assigned to normal control, H. pylori-inoculated group (negative control) and H. pylori-inoculated group receiving triple therapy consisting of omeprazole [2.035 mg/kg body weight (b.w)], amoxicillin (102.80 mg/kg b.w) and clarithromycin (51.37 mg/kg b.w) (n=6/group). H. pylori infection developed for four weeks after inoculation, followed by two-week triple therapy. At the end of the treatment period, femoral bones of the rats were harvested for analysis. Bone mineral density and content of the femurs were determined using dual-energy X-ray absorptiometry, while bone strength was measured with a universal mechanical tester.ResultsBone mineral content was significantly lower in the negative control group compared to the triple therapy group (p=0.014). Triple therapy decreased strain (vs negative control, p=0.002) and displacement of the femur (vs normal control, p=0.004; vs untreated control, p=0.005). No significant difference was observed in other parameters among the study groups (p>0.05).ConclusionShort-term triple therapy increases bone mineral content but decreases bone strength of rats. Skeletal prophylaxis should be considered for patients on short-term triple therapy containing PPI.

Comparison of Proton Pump Inhibitor and Triple Therapy Regimen for Laryngospharyngeal Reflux Disease.

Laryngopharyngeal reflux is retrograde flow of contents of the stomach to the larynx and the pharynx. The study aims to compare two regimens (proton pump inhibitor monotherapy versus triple therapy) on the outcome of Helicobactor pylori positive laryngopharyngeal reflux disease. The presence of laryngopharyngeal reflux was determined by reflux symptom index and reflux finding score. The presence of Helicobactor pylori in the tissue was confirmed by rapid urease test. All urease test negative laryngopharyngeal reflux patients were given a course of proton pump inhibitors and results were evaluated. All urease test positive patients were divided into two groups. One group was given a course of proton pump inhibitors and another group was given a course of triple therapy and the results were compared. A total number of 704 laryngopharyngeal reflux patients were screened for urease test. Among them 138 patients (19.6 %) were urease test negative and were given proton pump inhibitor therapy. Improvement in both reflux finding score (average score 11.75) and reflux symptom index (average score 5.25) score was observed after 3 months with p-value<0.05. In urease test positive patients, improvement in scores was observed in both proton pump inhibitors and triple therapy group, however marked improvement in the clinical features was observed in triple therapy group with p-value<0.05. The study reveals association between laryngopharyngeal reflux and Helicobactor pylori. Proton pump inhibitor therapy is sufficient if no Helicobactor pylori is detected, however incase of presence of Helicobactor pylori, triple therapy gives better results.

Outcomes in relation to antithrombotic therapy among patients with atrial fibrillation after percutaneous coronary intervention.

BackgroundsWe investigated the prognostic impact of antithrombotic regimens at 1-year after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF).Method and resultsA total of 13,278 AF patients who underwent PCI from 2009 to 2013 were selected from Korean National Health Insurance Service database. Patients were categorized by antithrombotic regimens at 1-year after PCI: (1) OAC with or without single antiplatelet (OAC±SAPT); (2) triple therapy (TT) and (3) antiplatelets (APT) only. After propensity score matching, composite ischaemia (death, myocardial infarction, and stroke), composite bleeding (intracranial hemorrhage and gastrointestinal bleeding), and a composite clinical outcome (composite ischaemia and bleeding) were compared. Of total population, 1,100 (8.3%), 746 (5.6%), and 11,432 (86.1%) were treated with OAC±SAPT, TT, and APT only, respectively. Compared to OAC±SAPT group, the TT group had significantly higher risk of the composite clinical outcome (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.00–2.13) attributed to a higher trend in both ischaemia (HR 1.63, 95% CI 0.99–2.67) and bleeding (HR 1.22, 95% CI 0.69–2.13). The APT only group showed a higher risk of ischaemia (HR 1.85, 95% CI 1.25–2.74), despite a lower risk of bleeding (HR 0.55, 95% CI 0.32–0.94) compared to OAC±SAPT group.ConclusionsOAC±SAPT was associated with better clinical outcomes compared to TT or APT only treatments, beyond 1-year after PCI among Asians with AF.

Could “triple-therapy” considered as a novel-optimal treatment model for acute bipolar depression? A prospective real-world research in China

BackgroundResults of researches of bipolar depression treatment are inconsistent and to our knowledge, no study has previously revealed an optimal treatment model for bipolar depression in the real-world through a prospective way. ObjectiveTo find out an optimal treatment model for bipolar depression in the real-world by evaluating the effect of different treatment models: monotherapy, double-therapy and triple-therapy. Designand Intervention: This 12 or 16-week, multi-center, real-world clinical study was conducted at 15 study sites (inpatient or outpatient department) in West China and a total of 573 patients completed the follow-up. During the study weeks, all researchers could choose a most proper treatment model freely basing on the evaluation of patient's symptoms and complete the follow-up according to the procedure. Main outcomes and measuresThe primary outcomes were baseline-to–endpoint change in Montgomery-Asberg Depression Rating Scale (MADRS) total score and the constituent ratio of effects. Total score change in Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) from baseline to endpoint, treatment-emergent mania rate and severe adverse events rate were used as secondary outcomes. ResultsDuring all study weeks, all the 3 groups showed a statistically significant improvement in MARDS, YMRS and CGI (P＜0.001), but the triple-therapy group showed much more effective in significant response and response rates at endpoint than double-therapy group and monotherapy group (P＜0.001) with lower treatment-emergent mania rates (P = 0.001). At week 4, mean scores of MARDS in triple-therapy group are statistically significant lower than monotherapy group (P = 0.013) and at the endpoint, mean scores of MARDS in triple-therapy group are statistically significant lower than both double-therapy and monotherapy groups (P = 0.011). The severe adverse events rates are rare in all the 3 groups at week 4 and endpoint, and the rate of dry mouth in triple-therapy group at week 4 is statistically significant lower than the other 2 groups (P = 0.002). ConclusionsTriple-therapy is more effective in treating bipolar depression than double-therapy and monotherapy model with a lower risk of developing manic symptoms. Trial registrationChinese Clinical Trial Registry. Identifier: ChiCTR1800019064.

Abstract 4449: Plinabulin, a microtubule destabilizing agent, improves tumor control by enhancing dendritic cell maturation and CD8 T cell infiltration in combination with immunoradiotherapy

Abstract There are theoretical benefits of combining immune checkpoint blockade with radiotherapy, however, there are few indications that such combinations have translated to significant clinical benefit to patients. There is an unmet need to further enhance the effectiveness of these “immunoradiotherapy” combinations. We hypothesize that enhancing antigen presentation through augmenting dendritic cell (DC) activation could potentially improve the effectiveness of immunoradiotherapy. Towards this end, we have investigated the potential for combining the microtubule destabilizing first-in-class agent Plinabulin as the candidate DC activator, with radiotherapy and anti-PD1 immunotherapy (αPD1). First, we investigated how DCs could be affected by Plinabulin and irradiation in in vitro assays. We irradiated SP37A3 and XS106 DC lines with 10Gy and added Plinabulin to those cells. With the addition of Plinabulin, the phosphorylation of JNK and NFκB was upregulated and DC maturation was promoted with high MHC-II, CD86, CD80 and CD40 surface expressions (p&amp;lt;0.05, Dunnett's test). Combining Plinabulin and radiotherapy further augmented the response, particularly in sequence with plinabulin but not in combination. In in vivo models. TSA syngeneic breast cancer cells were implanted to the flank of BALB/c mice, irradiated with 24Gy/3fr, and treated with αPD1 and Plinabulin. There were no anti-tumoral effects with αPD1 alone, Plinabulin alone, and αPD1+Plinabulin groups. However, triple therapy showed much stronger tumor regression than the double therapy of irradiation and αPD1. Tumors were collected from the mice at 2.5-3 weeks after the irradiation and dissociated tumor cells were analyzed for DC activation and immune repertoire using flow cytometry. The percentage of CD8 T cells and CD86+ DCs in the tumor were significantly increased in the triple therapy group that were not seen for the monotherapy or bimodal therapy groups (p&amp;lt;0.05, Dunnett's test). Our findings may serve as a rationale for establishing clinical trial designs of synergistic combinational approaches to enhance immunoradiotherapy. Citation Format: Shinya Neri. Plinabulin, a microtubule destabilizing agent, improves tumor control by enhancing dendritic cell maturation and CD8 T cell infiltration in combination with immunoradiotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4449.

Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD

BackgroundTriple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.MethodsIn a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.ResultsThe modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide–formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Similarly, the rate was significantly lower with 160-μg–budesonide triple therapy than with glycopyrrolate–formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide–formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P=0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate–formoterol group.ConclusionsTriple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.)

COMPARISON OF EFFECTIVENESS OF STANDARD TRIPLE THERAPY VERSUS BISMUTH-BASED THERAPY FOR THE MANAGEMENT OF PEPTIC ULCER DISEASE DUE TO HELICOBACTER PYLORI

Objective: Helicobacter pylori is the primary agent causing peptic ulcer, therefore imposing a significant impact on health elated quality of life, consequently affecting nearly 50% of global population. The objective of this study is to determine and assess the effectiveness of triple therapy versus bismuth containing quadruple therapy for eradication of peptic ulcer disease due to H. pylori.&#x0D; Methods: A prospective randomized observational study was conducted at Princess Esra Hospital, Department of Gastroenterology for a period of 6 months. A total of 100 patients were randomly allocated in tow groups. The data were assessed using various parameters. H. pylori eradication was validated using rapid urease test done at the start treatment 4 weeks after the completion.&#x0D; Results: A total of 100 patients were recruited in the study. In triple therapy group medication adherence rate was found to be 82% in triple and 92% in quadruple therapy. The eradication rate was assessed using Chi-square test it was 82% and 97% in triple and quadruple therapy group, respectively. Hence, the difference was found to be statistically significant value &lt;0.005. In addition, increased recurrence rate has been observed in triple therapy (17%) in contrast with quadruple therapy (2%).&#x0D; Conclusion: Addition of bismuth to significant triple therapy improves cure rates with minimal side effects. Interestingly, we observed that when bismuth was added, it produced a significant higher eradication rate (97%) when compared with standard triple therapy (82%). According to our study, bismuth is highly effective treatment of peptic ulcer disease.

Androgen receptor targeted therapy sensitizes tumor bearing mice to effective immunotherapy

Abstract Sex hormones impact both the innate and adaptive immune response, contributing to differences in autoimmune diseases, response to infection, and cancer incidence between males and females. Androgens are known to exert a general immunosuppressive effect. Historically, immune checkpoint blockade (ICB) has not proven to be efficacious in patients with prostate cancer despite standard of care consisting of androgen deprivation therapy (ADT). Upon disease progression, men will be treated with second line ADT therapy; some of which can prevent androgen receptor transcriptional activity. One such drug is enzalutamide. Given T cells express AR, we hypothesized that enzalutamide treatment would relieve the immunosuppressive effects of androgens on T cells, rendering them more responsive to immunotherapy. In the studies presented, we sensitize castration resistant prostate cancer tumor bearing mice to effective ICB with a combination of castration and enzalutamide. This combination therapy leads to ~40% tumor rejection and long-term survival; an effect that is dependent on CD8 T cells. These tumor infiltrating CD8 T cells made 6-fold more IFNγ within the tumor in the triple therapy group compared to control group. Surprisingly, this combination therapy showed efficacy in the androgen independent sarcoma tumor model MCA-205. Using in vitro and in vivo assays, we show that enzalutamide has a direct effect on T cell function. Taken together, our data suggests that ADT, and specifically enzalutamide treatment, can sensitize tumor bearing animals to effective immune checkpoint blockade and allow for tumor control by T cells.

Treatment of primary biliary cholangitis with ursodeoxycholic acid, prednisolone and immunosuppressants in patients not responding to ursodeoxycholic acid alone and the prognostic indicators

We reviewed the medical records of primary biliary cholangitis patients who were diagnosed by liver biopsy and treated with the corresponding treatment. We evaluated the therapeutic effect and long-term prognostic indicators. This observational cohort study enrolled 80 eligible patients diagnosed by liver biopsy between December 2013 and December 2018 in our department. UDCA monotherapy or UDCA added to prednisolone and immunosuppressant triple therapy was prescribed to patients. We analyzed and compared the demographic characteristics, biochemistry profiles, immune parameters, and noninvasive liver fibrosis assessments at baseline as well as the treatment efficacy, long-term outcomes and adverse effects at baseline and at each visit between the two groups. The indicators that could affect prognosis were assessed. Thirty-eight primary biliary cholangitis patients received UDCA monotherapy (group A), and another 42 patients received UDCA, prednisolone and immunosuppressant triple therapy (group B). After therapy, all patients showed significant improvements in liver biochemical parameters, immune indicators, and noninvasive fibrosis indicators (Fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI)), all P values<0.0001. The Mayo score also decreased significantly after treatment (P=0.022). Triple therapy was more effective, and there was a significant difference between the two groups. In addition, multivariate analysis showed that anti-gp210 antibody positivity; antimitochondrial antibody (AMA) negativity; high alkaline phosphatase (ALP), total bilirubin (TBIL) and globulin levels; and a severe degree of fibrosis at baseline were independent predictors of a poor prognosis. Triple therapy was a treatment option for UDCA-refractory PBC patients. Anti-gp210 antibody positivity; AMA negativity; high ALP, TBIL and globulin levels; and a severe degree of fibrosis at baseline were associated with a poor prognosis.

Antithrombotic Strategies in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention: A Systemic Review and Network Meta-Analysis of Randomized Controlled Trials.

Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35–0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05–0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.

Risk of Cardiovascular Outcomes and Antihypertensive Triple Combination Therapy Among Elderly Patients with Hypertension Enrolled in a Medicare Advantage Plan (MAP).

The aim was to evaluate the risk of cardiovascular-specific hospitalizations with different types of antihypertensive triple combination therapy among patients enrolled in a Medicare Advantage Plan (MAP). A retrospective cohort study was conducted among patients with hypertension enrolled in a Texas MAP between January 2014 and December 2016. Antihypertensive combination therapy users were classified into three treatment groups: single-pill triple combination, fixed-dose dual combination plus a third agent, and free triple combination. Group differences were assessed using Chi-square tests for binary variables and Student's t tests for continuous variables. Cox proportional hazards model was performed to assess the association between type of combination therapy and risk of cardiovascular-specific hospitalization adjusting for potential confounders. A total of 10,836 triple combination users were identified. The risk of cardiovascular disease (CVD) hospitalization for the fixed-dose dual combination plus a third agent group [hazard ratio (HR) 3.82, 95% confidence interval (CI) 1.80-8.12] and for the free triple combination therapy group (HR 3.65, 95% CI 1.43-9.31) was significantly higher than for the single-pill triple combination group. Single-pill triple combination therapy was significantly associated with a lower risk of CVD hospitalizations in comparison to other types of triple combination therapy.

CXCR1/2 blockade to enhance response to immune checkpoint inhibition in an aggressive orthotopic pancreatic adenocarcinoma model.

19 Background: Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer related deaths, with the incidence expected to rise in the coming years. Despite conventional chemotherapy and advances in immune checkpoint blockade, 5 year survival remains a dismal 8%. Intratumoral accumulation of granulocytic myeloid derived suppressor cells (G-MDSC) pose a significant barrier to treatment as they contribute to immune evasion by PDAC and correlate with poor prognosis. The ELR+ CXC chemokine receptors CXCR1 and CXCR2 (CXCR1/2) contribute to peripheral neutrophil migration into tissues and have been implicated in tumor mediated G-MDSC recruitment to the tumor microenvironment. Here we present our findings using an orally dosed CXCR1/2 inhibitor, SX-682, in an orthotopic PDAC model. Methods: C57BL/6 mice underwent orthotopic injections with KP2 cells. Mice were randomized into five groups (Table) receiving three weeks of FOLFIRINOX with combinations of SX-682 and/or checkpoint inhibition (anti-PD1/anti-CTLA4). FOLFIRINOX was dosed weekly for three weeks. Checkpoint inhibition was administered twice weekly. Chow weights were monitored for consumption of SX-682. Results: The simultaneous administration of FOLFIRINOX with SX-682 combined with checkpoint inhibition (triple therapy) resulted in a significant increase in survival compared to other groups (p = 0.0001). Notably, there was a significant increase in survival with triple therapy versus FOLFIRINOX plus checkpoint alone (p = 0.0259). Median survival of the triple therapy group was 42.5 days, compared to 37 days with checkpoint inhibition (p = &lt;0.05). There were no differences in chow consumption between the control and medicated chow groups. Conclusions: CXCR1/2 blockade combined with immune checkpoint inhibition and first line chemotherapy significantly enhanced survival in our PDAC mouse model. Thus, CXCR1/2 inhibition with SX-682 represents a promising target for clinical intervention in PDAC. [Table: see text]

Efficacy and Cost-effectiveness Comparison of 10-Day, 14-Day Sequential Versus 14-Day Triple Therapies for Treating Helicobacter pylori Infection in Egyptian Patients.

The aim of this study was to clarify whether 10-day or 14-day sequential therapy (ST) can replace conventional triple therapy (TT) as a first-line treatment in Egypt. Antimicrobial resistance has decreased the eradication rates for Helicobacter pylori infection worldwide. Patients who tested positive for H. pylori infection were randomly assigned to the 14-day triple-therapy group (n=34), 10-day ST group (n=34), or 14-day ST group (n=35). Sequential treatment includes lansoprazole 30 mg and amoxicillin 1000 mg, both twice for 5 or 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and tinidazole 500 mg, each twice for 5 or 7 days. Triple treatment consists of lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1000 mg, each twice for 14 days. Six weeks after treatment discontinuation, patients were examined by the urea breath test. Eradication rates, the incidence of adverse effects, compliance, and cost-effectiveness were evaluated. The eradication rate was 90% with 10-day ST, 96.7% with 14-day ST, and 63.3% for TT (P=0.001). Mild tolerated adverse effects occurred in the 3 groups. The cost-effectiveness ratio was 2194 LE, 1241 LE, 1157 LE for standard triple therapy, 10-day, and 14-day ST, respectively. Sequential therapies for 10 or 14 days are more cost-effective than standard TT, with 14-day ST being the most cost-effective. Accordingly, ST might replace TT as a first-line treatment for H. pylori infection in Egyptian patients.