Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up

AIDS ◽  
2002 ◽  
Vol 16 (7) ◽  
pp. 1051-1058 ◽  
Author(s):  
Robert S. Hogg ◽  
Katherine Heath ◽  
David Bangsberg ◽  
Benita Yip ◽  
Natasha Press ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Triple Combination ◽  
Triple Combination Therapy

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

Diabetes Care ◽  
2020 ◽  
pp. dc200978
Author(s):  
Muhammad Abdul-Ghani ◽  
Curtiss Puckett ◽  
John Adams ◽  
Ahmad Khattab ◽  
Gozde Baskoy ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
New Onset

P4160Safety and efficacy of triple combination therapy with parenteral prostanoids in patients with Eisenmenger physiology

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M D'Alto ◽  
O H Balint ◽  
G Giannakoulas ◽  
E Romeo ◽  
P Argiento ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Status ◽  
Functional Class ◽  
Right Atrial ◽  
Eisenmenger Syndrome ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Test Distance ◽  
6 Minute Walk Test

Abstract Aim While combination therapy is currently strongly advocated for idiopathic pulmonary arterial hypertension (PAH) patients, evidence to support its use in patients with PAH related to congenital heart disease (CHD), especially patients with Eisenmenger syndrome, is lacking. We evaluated the efficacy and safety of sequential triple combination therapy with parenteral prostanoids after failure of double oral therapy in patients with PAH-CHD and Eisenmenger physiology. Methods This is an international, multicentre, retrospective cohort study conducted in adult patients with Eisenmenger physiology on double oral PAH therapy in whom intravenous or subcutaneous prostanoid treatment was added due to clinical deterioration or failure to reach the treatment goals. Clinical status, 6-minute walk test distance (6MWD), biomarkers and haemodynamics were assessed at baseline and during the follow-up. Results A total 28 patients with Eisenmenger syndrome (6 [21%] male, age 37.6±14.3 years) were included. A post-tricuspid shunt was present in 16 (57%), 86% of whom had a ventricular septal defect. The majority (89%) were treated with subcutaneous treprostinil. At 27±14 months follow-up, WHO functional class improved in 18 (64%), remained unchanged in 8 (29%), and deteriorated in 2 (7%) patients. There was also an increase in 6MWD (mean 339±145 versus 233±140m, p=0.0001, fig 1A) and a reduction in NT-proBNP levels (median 1125 [123–5882] versus 3087 [234–7428] pg/mL, p<0.0001, fig 1B). On follow-up cardiac catheterization, an improvement in right atrial pressure (8±2 versus 11±5 mmHg, p=0.01), mean pulmonary artery pressure (68±12 versus 72±17 mmHg, p=0.005), cardiac index (2.3±0.3 versus 2.0±0.5 l/min/m2, p=0.005, fig 1C), and pulmonary vascular resistance (17±7 versus 21±10, p=0.008, fig 1D), was observed compared to baseline. No patients discontinued treatment. Five (18%) patients died during follow up. Figure 1 Conclusions Triple combination therapy with subcutaneous treprostinil or endovenous epoprostenol in patients with Eisenmenger syndrome is safe and well tolerated at 2 years follow-up, resulting in a significant improvement in clinical status, exercise tolerance and haemodynamics.

4972Upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous treprostinil in incident patients with severe pulmonary arterial hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M D'Alto ◽  
E Romeo ◽  
P Argiento ◽  
R Badagliacca ◽  
S Papa ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Arterial Compliance ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Pulmonary Arterial

Abstract Aim Current treatments strategies for high-risk patients with pulmonary arterial hypertension (PAH) are based on the use of parenteral prostanoids. The evidence to support triple upfront combination therapy remains largely based on expert consensus or small studies. Aim of this study was to evaluate the efficacy and safety of an upfront triple combination therapy with ambrisentan, tadalafil and subcutaneous (sc) treprostinil in patients with severe PAH. Methods This is a multi-center retrospective analysis of patients with newly diagnosed severe PAH treated with upfront triple combination therapy with ambrisentan, tadalafil and sc treprostinil between 2014 and 2018. Clinical evaluations, WHO functional class (FC), 6-min walk distance, biomarkers and right heart catheterization were collected from the patients' medical records at baseline and during the follow-up. Results Overall, 20 patients (mean age 44±15 years, 15 female) were included. Over a median follow-up of 12 months, all patients were still alive on triple combination therapy. At baseline 11 patients were in WHO-FC 3 and 9 patients in WHO-FC 4. At follow-up, WHO-FC (2.0±0.5 vs 3.5±0.5, p<0.001, improved in all: 2, 16, and 2 patients in FC 1, 2 and 3, respectively), exercise capacity (431±67 vs 152±130 m, p<0.001), NT-proBNP (423±260 vs 3492±1864 pg/ml; p<0.001), and haemodynamics (right atrial pressure 5±2 vs 13±3 mmHg, p<0.001; mean pulmonary artery pressure 42±5 vs 60±9 mmHg, p<0.001; cardiac index 3.5±0.8 vs 1.8±0.3 l/min/m2, p<0.001; pulmonary vascular resistance 5.5±1.3 vs 16.4±4.4 Wood units, p<0.001; pulmonary arterial compliance 2.5±0.9 vs 0.8±0.3 ml/mmHg, p<0.001) significantly improved compared with baseline. No patient discontinued the therapy due to serious adverse events. Conclusions Triple upfront combination therapy with ambrisentan, tadalafil and sc treprostinil is safe and offers clinical and heamodynamics benefits in incident patients with severe PAH.

scholarly journals Upfront triple combination therapy in severe paediatric pulmonary arterial hypertension

2020 ◽  
pp. 2001120
Author(s):  
Meindina G. Haarman ◽  
Marilyne Lévy ◽  
Marcus T.R. Roofthooft ◽  
Johannes M. Douwes ◽  
Theresia R. Vissia-Kazemier ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
World Health ◽  
Walking Distance ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Long Term Outcome ◽  
Pulmonary Arterial

IntroductionTreatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH.MethodsChildren diagnosed with PAH between 2010 and 2019 and started with uTCT were included. World Health Organization Functional Class (WHO-FC), haemodynamics, echocardiography, six-minute walking distance, and serum level of N-terminal-Pro-Brain-Natriuretic-Peptide were assessed at baseline, after three and 6 months and at last available follow-up. Events were defined as death, lung transplantation or Potts shunt.ResultsTwenty-one children (median age 4.8 years (2.5–12.8), 57% females) were included. All children except one were in WHO-FC III or IV (28% and 67%, respectively). After 3 months, one child had died and one child had received a Potts shunt. The remaining 19 children showed clinical and echocardiographic improvement, which persisted at 6 months. Children with idiopathic and heritable PAH showed one-, two-, and three-year transplant-free survival estimates of 100%, 94%, and 87%, albeit 47% of them receiving a Potts shunt during follow-up.ConclusionsChildren with severe PAH, but not pulmonary veno-occlusive disease, improved significantly with uTCT and showed beneficial up to 3-year survival rates, albeit 47% of them receiving a Potts shunt during follow-up. The role of a Potts shunt in conjunction to uTCT in paediatric PAH needs to be further established.

scholarly journals IMMU-19. TARGETING GLIOBLASTOMA IMMUNOSUPPRESSION AND TREATMENT RESISTANCE WITH IBRUTINIB IN COMBINATION WITH STEREOTACTIC RADIATION AND IMMUNE CHECKPOINT BLOCKADE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii108-ii108
Author(s):  
Jayeeta Ghose ◽  
Baisakhi Raychaudhuri ◽  
Kevin Liu ◽  
William Jiang ◽  
Pooja Gulati ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Median Survival ◽  
Immune Checkpoint ◽  
Survival Benefit ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Control Group ◽  
Triple Combination ◽  
Triple Combination Therapy

Abstract BACKGROUND Glioblastoma (GBM) is associated with systemic and intratumoral immunosuppression. Part of this immunosuppression is mediated by myeloid derived suppressor cells (MDSCs). Preclinical evidence shows that ibrutinib, a tyrosine kinase inhibitor FDA approved for use in chronic lymphocytic leukemia and known to be CNS penetrant, can decrease MDSC generation and function. Also, focal radiation therapy (RT) synergizes with anti-PD-1 therapy in mouse GBM models. Thus, we aimed to test the combination of these approaches on immune activation and survival in a preclinical immune-intact GBM mouse model. METHODS C57BL/6 mice intracranially implanted with the murine glioma cell line GL261-Luc2 were divided into 8 groups consisting of treatments with ibrutinib, RT (10 Gy SRS), or anti-PD-1 individually or in each combination (along with a no treatment control group). Immune cell subset changes (flow-cytometry) and animal survival (Kaplan-Meier) were assessed (n=10 mice per group). RESULTS Median survival of the following groups including control (28 days), ibrutinib (27 days), RT (30 days) or anti-PD-1 (32 days) showed no significant differences. However, a significant improvement in median survival was seen in mice given combinations of ibrutinib+RT (35 days), ibrutinib+anti-PD-1 (38 days), and triple therapy with ibrutinib+RT+anti-PD-1 (48 days, p &lt; 0.05) compared to controls or single treatment groups. The reproducible survival benefit of triple combination therapy was abrogated in the setting of CD4+ and CD8+ T cell depletion. Contralateral intracranial tumor re-challenge in long-term surviving mice suggested generation of tumor-specific immune memory responses. The immune profile of the tumor microenvironment (TME) showed increased cytotoxic CD8+ T cells and decreased MDSCs and regulatory T cells in the triple combination therapy mice compared to controls. CONCLUSION The combination of ibrutinib, focal RT, and anti-PD-1 immune checkpoint blockade led to a significant survival benefit compared to controls in a preclinical model of GBM.

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