Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON

Crestani, Bruno; Huggins, John T.; Kaye, Mitchell; Costabel, Ulrich; Glaspole, Ian; Ogura, Takashi; Song, Jin Woo; Stansen, Wibke; Quaresma, Manuel; Stowasser, Susanne; Kreuter, Michael

doi:10.1016/s2213-2600(18)30339-4

Cited by 184 publications

(221 citation statements)

References 24 publications

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“…No new safety concerns have been raised during this follow-up and the incidence of MI and major adverse cardiac events was lower in the real-world populations (Table 2) [15, 20, 33]. There was also no evidence of QT-prolongation with nintedanib treatment in INPULSIS or TOMORROW (pooled data; nintedanib: n = 723, placebo: n = 508).…”

Section: Nintedanib Use In Patients With Additional Risk Factorsmentioning

confidence: 94%

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a dismal survival rate of only 3 years and no curative pharmacological therapy. The recent approval of 2 anti-fibrotic drugs (nintedanib and pirfenidone) that slow disease progression has provided some hope for patients. However, effectively managing anti-fibrotic treatment can be a challenge due to tolerability issues, the presence of pulmonary and extra-pulmonary comorbidities, and the need for concomitant medications in many patients. In general, making clear evidence-based decisions can be difficult for physicians because patients with comorbidities are often excluded from clinical trials. Since currently anti-fibrotic drugs are the only effective therapeutics capable of slowing disease progression, it is imperative that all treatment options are thoroughly evaluated and exhausted in each individual, irrespective of complicating factors, to permit the best outcome for the patient. In this review, we present data from clinical trials, post hoc analyses, post-marketing surveillance, and real-world studies that are relevant to the management of nintedanib treatment. In addition, we also provide practical recommendations developed by a multidisciplinary panel of experts for the management of nintedanib treatment in patients with IPF associated complications and those experiencing gastrointestinal side effects.

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Section: Nintedanib Use In Patients With Additional Risk Factorsmentioning

confidence: 94%

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

et al. 2018

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“…It has previously been reported that TKIs such as imatinib or sunitinib can cause cardiovascular side effects including heart failure, LV dysfunction, conduction abnormalities, QT prolongation, acute coronary syndromes, myocardial injury, arterial thrombosis, and hypertension . Patients with significant cardiovascular disease were actively excluded from the nintedanib trials in IPF but follow‐up of the long‐term use of nintedanib in IPF haas been associated with major adverse cardiovascular events in the order of 3.6 events per 100 patient exposure‐years .…”

Section: Discussionmentioning

confidence: 99%

“…Nintedanib is an intracellular multi‐target tyrosine kinase inhibitor (TKI), whose targets include platelet‐derived growth factor receptors α and β, vascular endothelial growth factor receptors 1, 2, 3, and fibroblast growth factor receptors 1, 2, and 3 . The use of nintedanib has been demonstrated to significantly reduce disease progression in idiopathic pulmonary fibrosis (IPF) but serious adverse cardiovascular events can occur . We report the first case of left ventricular (LV) dysfunction in a patient with IPF on nintedanib.…”

Section: Introductionmentioning

confidence: 99%

Left ventricular dysfunction in an idiopathic pulmonary fibrosis patient on nintedanib

Imai

Tomishima

2020

Respirology Case Reports

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Nintedanib, a tyrosine kinase inhibitor, is approved for the treatment of idiopathic pulmonary fibrosis. We report a case of left ventricular dysfunction in a patient with idiopathic pulmonary fibrosis treated with nintedanib, which recovered after cessation of nintedanib. Nintedanib may induce left ventricular dysfunction, and early recognition is important since this condition is potentially reversible.

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“…Vancheri et al 43 also reported on the safety of combination therapy, and found that gastrointestinal adverse events occurred in 69.8% of patients treated with nintedanib with add-on pirfenidone and 52.9% of patients treated with nintedanib. Crestani et al 44 examined the long-term safety of nintedanib. In a placebo-controlled, open label, extension of the INPULSIS trials they found that diarrhea was the most common adverse event, with 15% of the patients discontinuing because of it.…”

Section: Discussionmentioning

confidence: 99%

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis

Skandamis

Kani

Markantonis

et al. 2019

Journal of Drug Assessment

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Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-tohead comparisons. Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline 10% (pirfenidone OR ¼ 0.54 [95% CI ¼ 0.37-0.80], NNTB ¼ 9 [95% CI ¼ 7-22]; nintedanib OR ¼ 0.59 [95% CI ¼ 0.41-0.84], NNTB ¼ 9 [95% CI ¼ 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR ¼ 0.91 [95% CI ¼ 0.45-2.03]) or dropouts (OR ¼ 0.75 [95% CI ¼ 0.33-1.27]). Nintedanib showed an effect on dropouts, OR ¼ 1.61 (1.13-2.28) and . Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments. ARTICLE HISTORY

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Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON

Cited by 184 publications

References 24 publications

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

Nintedanib in Idiopathic Pulmonary Fibrosis: Practical Management Recommendations for Potential Adverse Events

Left ventricular dysfunction in an idiopathic pulmonary fibrosis patient on nintedanib

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis

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