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Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis.

Corte T, Bonella F, Crestani B, Demedts MG, Richeldi L, Coeck C, Pelling K, Quaresma M, Lasky JA - Respir. Res. (2015)

Bottom Line: Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%).Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively.Nintedanib had a manageable safety and tolerability profile in patients with IPF.

View Article: PubMed Central - PubMed

Affiliation: Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. tameracorte@mac.com.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function.

Methods: Using pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS(®) trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials.

Results: One thousand and sixty- one patients were treated (nintedanib 638; placebo 423). Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%). Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively. Diarrhea was the most frequent adverse event, reported in 62.4% of patients in the nintedanib group versus 18.4% in the placebo group; however, only 4.4% of nintedanib-treated patients discontinued trial medication prematurely due to diarrhea. Monitoring of liver enzymes before and periodically during nintedanib treatment was recommended so that liver enzyme elevations could be managed through dose reduction or treatment interruption.

Conclusion: Nintedanib had a manageable safety and tolerability profile in patients with IPF. Recommendations for adverse event management minimized permanent treatment discontinuations in the INPULSIS(®) trials.

Trial registration: clinicaltrials.gov NCT01335464 and NCT01335477.

No MeSH data available.


Related in: MedlinePlus

Algorithm for the management of hepatic enzyme elevations in the INPULSIS® trials. *Defined as increase in hepatic transaminases (AST or ALT) to ≥3 x ULN, and i) total bilirubin >1.5 ULN or ii) INR >1.5 or iii) appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). In the INPULSIS® trials, routine clinical laboratory testing was undertaken at screening and weeks 2, 4, 6, 12, 18, 24, 30, 36, 44 and 52
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Fig2: Algorithm for the management of hepatic enzyme elevations in the INPULSIS® trials. *Defined as increase in hepatic transaminases (AST or ALT) to ≥3 x ULN, and i) total bilirubin >1.5 ULN or ii) INR >1.5 or iii) appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). In the INPULSIS® trials, routine clinical laboratory testing was undertaken at screening and weeks 2, 4, 6, 12, 18, 24, 30, 36, 44 and 52

Mentions: Eligible patients were randomized using a 3:2 ratio to receive nintedanib 150 mg bid or placebo for 52 weeks, followed by a 4-week follow-up period. There was no requirement for dose titration on initiation of treatment. Treatment interruption and/or dose reduction from 150 mg bid to 100 mg bid were allowed for the management of adverse events. For patients who had a dose interruption, treatment could be reinstituted at a dose of 150 mg bid or 100 mg bid after resolution of the adverse event. After a dose reduction, the dose could be re-escalated to 150 mg bid. Specific recommendations were provided to the investigators for the management of diarrhea (Fig. 1) and hepatic enzyme elevations (Fig. 2).Fig. 1


Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis.

Corte T, Bonella F, Crestani B, Demedts MG, Richeldi L, Coeck C, Pelling K, Quaresma M, Lasky JA - Respir. Res. (2015)

Algorithm for the management of hepatic enzyme elevations in the INPULSIS® trials. *Defined as increase in hepatic transaminases (AST or ALT) to ≥3 x ULN, and i) total bilirubin >1.5 ULN or ii) INR >1.5 or iii) appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). In the INPULSIS® trials, routine clinical laboratory testing was undertaken at screening and weeks 2, 4, 6, 12, 18, 24, 30, 36, 44 and 52
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4581488&req=5

Fig2: Algorithm for the management of hepatic enzyme elevations in the INPULSIS® trials. *Defined as increase in hepatic transaminases (AST or ALT) to ≥3 x ULN, and i) total bilirubin >1.5 ULN or ii) INR >1.5 or iii) appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%). In the INPULSIS® trials, routine clinical laboratory testing was undertaken at screening and weeks 2, 4, 6, 12, 18, 24, 30, 36, 44 and 52
Mentions: Eligible patients were randomized using a 3:2 ratio to receive nintedanib 150 mg bid or placebo for 52 weeks, followed by a 4-week follow-up period. There was no requirement for dose titration on initiation of treatment. Treatment interruption and/or dose reduction from 150 mg bid to 100 mg bid were allowed for the management of adverse events. For patients who had a dose interruption, treatment could be reinstituted at a dose of 150 mg bid or 100 mg bid after resolution of the adverse event. After a dose reduction, the dose could be re-escalated to 150 mg bid. Specific recommendations were provided to the investigators for the management of diarrhea (Fig. 1) and hepatic enzyme elevations (Fig. 2).Fig. 1

Bottom Line: Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%).Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively.Nintedanib had a manageable safety and tolerability profile in patients with IPF.

View Article: PubMed Central - PubMed

Affiliation: Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. tameracorte@mac.com.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterised by dyspnea and loss of lung function.

Methods: Using pooled data from the replicate, randomized, 52-week, placebo-controlled INPULSIS(®) trials, we characterized the safety and tolerability of nintedanib 150 mg twice daily in patients with IPF and described how adverse events were managed during these trials.

Results: One thousand and sixty- one patients were treated (nintedanib 638; placebo 423). Higher proportions of patients in the nintedanib group than the placebo group had ≥ 1 dose reduction to 100 mg bid (27.9% versus 3.8%) or treatment interruption (23.7% versus 9.9%). Adverse events led to permanent treatment discontinuation in 19.3% and 13.0% of patients in the nintedanib and placebo groups, respectively. Diarrhea was the most frequent adverse event, reported in 62.4% of patients in the nintedanib group versus 18.4% in the placebo group; however, only 4.4% of nintedanib-treated patients discontinued trial medication prematurely due to diarrhea. Monitoring of liver enzymes before and periodically during nintedanib treatment was recommended so that liver enzyme elevations could be managed through dose reduction or treatment interruption.

Conclusion: Nintedanib had a manageable safety and tolerability profile in patients with IPF. Recommendations for adverse event management minimized permanent treatment discontinuations in the INPULSIS(®) trials.

Trial registration: clinicaltrials.gov NCT01335464 and NCT01335477.

No MeSH data available.


Related in: MedlinePlus