Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis

Kuwana, Masataka; Blair, Christiana; Takahashi, Tomohiko; Langley, Jonathan; Coghlan, J. Gerry

doi:10.1136/annrheumdis-2019-216274

Cited by 49 publications

(32 citation statements)

References 33 publications

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“…The combination was well tolerated and considered safe. These data confirm recently revised treatment guidelines, suggesting that initial combined therapy for newly diagnosed patients, even when symptoms are mild, may be of value to clinicians [ 49 ].…”

Section: Resultssupporting

confidence: 83%

Future Treatment Options in Systemic Sclerosis—Potential Targets and Ongoing Clinical Trials

Bohdziewicz

Pawlik

Maciejewska

et al. 2022

JCM

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Systemic sclerosis is an autoimmune connective tissue disease characterized by vasculopathy and fibrosis of the skin and internal organs. The pathogenesis of systemic sclerosis is very complex. Mediators produced by immune cells are involved in the inflammatory processes occurring in the tissues. The currently available therapeutic options are often insufficient to halt disease progress. This article presents an overview of potential therapeutic targets and the pipeline of possible future therapeutic options. It is based on research of clinical trials involving novel, unestablished methods of treatment. Increasing knowledge of the processes and mediators involved in systemic scleroderma has led to the initiation of drug trials with therapeutic targets of CD28-CD80/86, CD19, CCL24, CD20, CD30, tumor necrosis factor (TNF), transforming growth factor β (TGF-β), B-cell activating factor (BAFF), lysophosphatidic acid receptor 1 (LPA1 receptor), soluble guanylate cyclase (sGC), Janus kinases (JAK), interleukin 6 (IL-6), endothelin receptor, and autotaxin. Data from clinical trials on these drugs indicate a significant potential for several new therapeutic options for systemic sclerosis in the upcoming future.

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Section: Resultssupporting

confidence: 83%

Future Treatment Options in Systemic Sclerosis—Potential Targets and Ongoing Clinical Trials

Bohdziewicz

Pawlik

Maciejewska

et al. 2022

JCM

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“…37 Several studies have reported the efficacy of up-front combination therapy to target 2 pathways simultaneously, thereby improving the clinical outcome of PH: death, hospitalization, and symptoms. 38,39 Furthermore, our study showed that early stabilization of PH hemodynamics could lower the incidence of CKD progression presumably through the improvement of cardiac output and renal perfusion. Another mechanism for the prominent effect on CKD progression of pulmonary vasodilator combination is their direct renoprotective effect.…”

Section: Discussionmentioning

confidence: 65%

Early combination of pulmonary vasodilators prevents chronic kidney disease progression in connective tissue disease‐associated pulmonary hypertension

et al. 2021

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Aim: Pulmonary hypertension (PH) and chronic kidney disease (CKD) are interdependent for their development and exacerbation. We evaluated the effect of PH on CKD progression in patients with connective tissue disease (CTD)-associated PH. Methods:We reviewed consecutive patients with CTD who were diagnosed with PH with right heart catheter (RHC) examinations in our hospital. Patients were divided into 2 groups according to the use of vasodilators: monotherapy or combination therapy. We further divided the patients with combination therapy into early and non-early combination groups. Early combination was defined as the addition of the second vasodilator within 1 month after starting the first drug. The clinical course of hemodynamics and CKD progression were compared.Results: Thirty-eight patients were included in the analysis: 10 were treated with monotherapy and 28 with combination therapy (14 with early and 14 with non-early).At baseline, patients who received combination therapy had a significantly higher mean pulmonary arterial pressure with RHC and a higher right ventricular systolic pressure (RVSP) with echocardiography (P = .04) and showed a greater improvement in RVSP after treatment than those who underwent monotherapy. The incidence of CKD progression was significantly lower in patients who received combination therapy than in those who received monotherapy (P = .05). Among patients who received combination therapy, the early combination group had a lower incidence of CKD progression than the non-early combination group (P = .03). Conclusions:Early combination therapy is associated with a lower incidence of CKD progression in patients with CTD-associated PH.

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“…In the recently published post hoc analysis of the modified intention to treat CTD-PAH patients included in the AMBITION study [ 8 ], an abbreviated version of the SPAHR/COMPERA risk assessment [ 19 , 20 ] based on three criteria (WHO-FC, NTproBNP and 6MWT), as well as the low-risk noninvasive criteria model used by the French registry [ 18 ] were applied. The authors concluded that these abbreviated versions may be useful in predicting PAH-related outcomes in patients with CTD-PAH, but that further research, including large patient cohorts for identifying the most optimal predictive tools, is warranted.…”

Section: Discussionmentioning

confidence: 99%

“…PAH is a serious complication in CTD and is associated with a highly unfavourable prognosis [3][4][5][6]. Despite improvement of functional parameters and survival rate by modern treatment, [7,8] the outcome of patients with CTD-PAH, and especially of those with systemic sclerosis associated PAH (SSc-PAH), remains poor [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Early risk prediction in idiopathicversusconnective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment

et al. 2021

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Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome, and performance of the ESC/ERS risk stratification tool in these patient groups.This retrospective analysis included incident patients with CTD-PAH (n=197, of which 64 had interstitial lung disease, ILD) or IPAH (n=305) enrolled in the Swedish PAH Register 2008–2019. Patients were classified as low, intermediate, or high risk at baseline, according to the “SPAHR-equation”. 1-year survival, stratified by type of PAH, was investigated by Cox proportional regression.At baseline, CTD-PAH patients had lower diffusing capacity for carbon monoxide and lower haemoglobin, but, at the same time, lower N-terminal prohormone-brain natriuretic peptide, longer 6 min walking distance, better hemodynamics, and more often a low-risk profile. No difference in age, WHO-FC, or renal function between groups was found. 1-year survival rates were 75, 82 and 83%, in patients with CTD-PAH with ILD, CTD-PAH without ILD, and IPAH, respectively. The 1-year mortality rates for low-, intermediate-, and high-risk groups in the whole cohort were 0, 18 and 34% (p<0.001), respectively. Corresponding percentages for CTD-PAH with ILD, CTD-PAH without ILD, and IPAH patients were: 0, 26, 67% (p=0.008); 0, 19, 39% (p=0.004); and 0, 16, 29% (p=0.001), respectively.The ESC/ERS risk assessment tool accurately identified low-risk patients but underestimated the 1-year mortality rate of CTD-PAH and IPAH patients assessed as having intermediate risk at diagnosis.

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Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis

Cited by 49 publications

References 33 publications

Future Treatment Options in Systemic Sclerosis—Potential Targets and Ongoing Clinical Trials

Future Treatment Options in Systemic Sclerosis—Potential Targets and Ongoing Clinical Trials

Early combination of pulmonary vasodilators prevents chronic kidney disease progression in connective tissue disease‐associated pulmonary hypertension

Early risk prediction in idiopathicversusconnective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment

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