Effect of anti-acid medication on reduction in FVC decline with nintedanib

Raghu, Ganesh; Crestani, Bruno; Bailes, Zelie; Schlenker‐Herceg, Rozsa; Costabel, Ulrich

doi:10.1183/13993003.congress-2015.oa4502

Cited by 22 publications

(16 citation statements)

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“…determined the safety and efficacy of nintedanib in patients with IPF suggests that patients treated with PPI at baseline may actually do worse (52). However, the presented data were results of a post hoc analysis comparing patients with IPF taking concomitant antacid medication (PPIs or H2RA) versus those who were not.…”

Section: Pulmonary Perspectivementioning

confidence: 55%

Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs

Ghebre

Raghu

2016

Am J Respir Crit Care Med

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The prevalence of abnormal acid gastroesophageal reflux (GER) is higher in patients with idiopathic pulmonary fibrosis (IPF) than in matched control subjects. Several studies demonstrated that more than one-third of patients with IPF have abnormal esophageal acid exposures. In addition, many of these studies indicate that the majority of patients with IPF have silent reflux with no symptoms of GER. Findings of abnormal reflux persist in a large proportion of patients with IPF placed on antacid therapy such as proton pump inhibitors (PPIs). This seemingly paradoxical observation suggests that either patients with IPF are somehow resistant to PPI-based intervention or PPIs are inherently unable to suppress acid GER. By contrast, patients with IPF who undergo Nissen fundoplication surgery are effectively relieved from the complications of GER, and retrospective studies suggest improved lung function. Retrospective, anecdotal data suggest a beneficial role of PPIs in IPF including stabilization of lung function, reduction in episodes of acute exacerbation, and enhanced longevity. The recent evidence-based guidelines for treatment of IPF approved conditional recommendation of PPIs for all patients with IPF regardless of their GER status. Recently, we have reported that PPIs possess antiinflammatory and antifibrotic activities by directly suppressing proinflammatory cytokines, profibrotic proteins, and proliferation of lung fibroblasts. Our study provides an alternative explanation for the beneficial effect of PPIs in IPF. In this Perspective, we reviewed emerging progress on antifibrotic effect of PPIs using IPF as a disease model. In addition, we summarized surgical and pharmacological interventions for GER and their downstream effect on lung physiology.

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Section: Pulmonary Perspectivementioning

confidence: 55%

Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs

Ghebre

Raghu

2016

Am J Respir Crit Care Med

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“…By contrast, in an analysis of the placebo arms in three pirfenidone trials, the use of antiacid treatment had no effect on the rate of FVC decline [46]. In a post hoc analysis of the two INPULSIS nintedanib studies, presented at the 2015 European Respiratory Society (ERS) International Congress, the use of concomitant antiacid therapy was actually associated with trends towards a worse outcome [47].…”

Section: Gastro-oesophageal Refluxmentioning

confidence: 90%

Comorbidities in interstitial lung diseases

2017

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Fibrosing lung disorders include a large number of diseases with diverse behaviour. Patients can die because of the progression of their illness, remain stable or even improve after appropriate treatment has been instituted. Comorbidities, such as acute and chronic infection, gastro-oesophageal reflux, pulmonary hypertension, lung cancer, cardiovascular diseases, and obstructive sleep apnoea, can pre-exist or develop at any time during the course of the disease and, if unidentified and untreated, may impair quality of life, impact upon the respiratory status of the patients, and ultimately lead to disease progression and death. Therefore, early identification and accurate treatment of comorbidities is essential.

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“…were investigated in the two replicate Phase III INPULSIS® trials [29]. Compared with placebo, nintedanib significantly reduced disease progression by reducing the annual rate of decline in forced vital capacity (FVC), with consistent treatment effects observed across subgroups defined by a variety of baseline characteristics including the use of corticosteroids [30] and anti-acid medications [31]. Investigator-reported acute exacerbations were reduced with nintedanib in INPULSIS®-2, but not in INPULSIS®-1.…”

Section: Introductionmentioning

confidence: 99%

Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis

et al. 2018

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Background: Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. Objectives: We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. Methods: Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. Results: At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were –78.9 and –187.6 mL/year in patients who received statins at baseline, and –127.9 and –237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (p = 0.9590). Conclusions: In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF.

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Effect of anti-acid medication on reduction in FVC decline with nintedanib

Cited by 22 publications

References 0 publications

Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs

Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs

Comorbidities in interstitial lung diseases

Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis

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