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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

Time to first diarrhea adverse event in the INPULSIS® trials
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Fig3: Time to first diarrhea adverse event in the INPULSIS® trials

Mentions: Diarrhea was the most frequently reported adverse event in the nintedanib group, reported in 62.4 % of patients compared with 18.4 % of patients in the placebo group. A summary of diarrhea adverse events and their clinical consequences is presented in Table 4. Almost all patients who reported diarrhea adverse events (nintedanib: 94.5 %, placebo: 97.4 %) reported events of mild or moderate intensity. Of patients who had ≥1 completed eCRF specific for diarrhea (n = 185 in the nintedanib group; n = 25 in the placebo group), most had <4 extra stools per day (nintedanib: 111 patients [60.0 %], placebo: 19 patients [76.0 %]). Bowel movements were most commonly characterized as watery with or without formed stool. Among patients who experienced a diarrhea adverse event, anti-diarrheal therapies (most commonly loperamide) were used by 55.3 % of patients in the nintedanib group and 25.6 % of patients in the placebo group during the on-treatment period. For most patients who reported diarrhea adverse events (nintedanib: 78.6 %, placebo: 98.7 %), the events resolved without the need for dose reduction or treatment interruption. A small proportion of patients had a permanent dose reduction (nintedanib: 68 patients [10.7 %], placebo: no patients) and/or discontinued trial medication prematurely due to diarrhea (nintedanib: 28 patients [4.4 %], placebo: 1 [0.2 %]). Among patients who experienced any diarrhea adverse events, most reported a single event (nintedanib: 60.3 %; placebo: 76.9 %) or 2 events (nintedanib: 26.4 %; placebo: 15.4 %). The median (minimum, maximum) duration of diarrhea events was 138.5 (1, 473) days in the nintedanib group and 7.0 (1, 453) days in the placebo group. For most patients with a diarrhea adverse event, the first onset occurred within the first 3 months of treatment (Fig. 3).Table 4


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)

Time to first diarrhea adverse event in the INPULSIS® trials
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Time to first diarrhea adverse event in the INPULSIS® trials
Mentions: Diarrhea was the most frequently reported adverse event in the nintedanib group, reported in 62.4 % of patients compared with 18.4 % of patients in the placebo group. A summary of diarrhea adverse events and their clinical consequences is presented in Table 4. Almost all patients who reported diarrhea adverse events (nintedanib: 94.5 %, placebo: 97.4 %) reported events of mild or moderate intensity. Of patients who had ≥1 completed eCRF specific for diarrhea (n = 185 in the nintedanib group; n = 25 in the placebo group), most had <4 extra stools per day (nintedanib: 111 patients [60.0 %], placebo: 19 patients [76.0 %]). Bowel movements were most commonly characterized as watery with or without formed stool. Among patients who experienced a diarrhea adverse event, anti-diarrheal therapies (most commonly loperamide) were used by 55.3 % of patients in the nintedanib group and 25.6 % of patients in the placebo group during the on-treatment period. For most patients who reported diarrhea adverse events (nintedanib: 78.6 %, placebo: 98.7 %), the events resolved without the need for dose reduction or treatment interruption. A small proportion of patients had a permanent dose reduction (nintedanib: 68 patients [10.7 %], placebo: no patients) and/or discontinued trial medication prematurely due to diarrhea (nintedanib: 28 patients [4.4 %], placebo: 1 [0.2 %]). Among patients who experienced any diarrhea adverse events, most reported a single event (nintedanib: 60.3 %; placebo: 76.9 %) or 2 events (nintedanib: 26.4 %; placebo: 15.4 %). The median (minimum, maximum) duration of diarrhea events was 138.5 (1, 473) days in the nintedanib group and 7.0 (1, 453) days in the placebo group. For most patients with a diarrhea adverse event, the first onset occurred within the first 3 months of treatment (Fig. 3).Table 4

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