Dataset Information

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil.

ABSTRACT:

Objective

Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population.

Methods

Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events.

Results

The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event.

Conclusion

In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

SUBMITTER: Pereira CAC

PROVIDER: S-EPMC8653976 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil.

Pereira Carlos Alberto de Castro CAC Baddini-Martinez José Antonio JA Baldi Bruno Guedes BG Jezler Sérgio Fernandes de Oliveira SFO Rubin Adalberto Sperb AS Alves Rogerio Lopes Rufino RLR Zonzin Gilmar Alves GA Quaresma Manuel M Trampisch Matthias M Rabahi Marcelo Fouad MF

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia 20190916 5

<h4>Objective</h4>Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population.<h4>Methods</h4>Patients ...[more]

PMID: 31531619

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Project description:BACKGROUND:The two 52-week INPULSIS trials investigated nintedanib versus placebo in patients with IPF, FVC ≥50% predicted and DLco 30-79% predicted. The 24-week INSTAGE trial investigated nintedanib plus sildenafil versus nintedanib alone in patients with IPF and DLco ≤35% predicted. We used data from INPULSIS and INSTAGE to compare the effects of nintedanib in patients with IPF with less versus more severe impairment in gas exchange at baseline. METHODS:Analyses were conducted in patients treated with nintedanib alone in the INPULSIS and INSTAGE trials and in patients treated with placebo in the INPULSIS trials. Outcomes included the rate of decline in FVC over 24 weeks, the proportions of patients who had a confirmed or suspected idiopathic acute exacerbation over 24 weeks, deaths over 24 weeks, and adverse events. Analyses were descriptive. RESULTS:In total, 638 and 136 patients received nintedanib alone in the INPULSIS and INSTAGE trials, respectively, and 423 patients received placebo in the INPULSIS trials. Rates of FVC decline were - 52.3 and - 66.7 mL/24 weeks in patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and - 102.8 mL/24 weeks in patients treated with placebo in INPULSIS. Confirmed or suspected idiopathic acute exacerbations were reported in 0.6 and 3.7% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 2.1% of patients treated with placebo in INPULSIS. Deaths occurred in 2.0, 11.0 and 1.9% of patients in these groups, respectively. Diarrhoea adverse events were reported in 52.5 and 48.5% of patients treated with nintedanib alone in INPULSIS and INSTAGE, respectively, and 16.1% of patients treated with placebo in INPULSIS. CONCLUSIONS:Based on data from the INSTAGE and INPULSIS trials, nintedanib had a similar effect on FVC decline over 24 weeks, and a similar safety and tolerability profile, in patients with IPF and more versus less severe impairment in gas exchange. These data support the use of nintedanib in patients with IPF who have advanced disease. TRIAL REGISTRATION:INPULSIS (NCT01335464 and NCT01335477); INSTAGE (NCT02802345).

Project description:IntroductionNintedanib is recommended for the treatment of idiopathic pulmonary fibrosis (IPF); however, treatment discontinuation due to adverse events (AEs) is common. A large-scale post-marketing surveillance study is investigating the real-world tolerability/safety of nintedanib in Japanese patients with IPF in routine clinical practice. Here, we report a 12-month interim analysis of this study.MethodsThe study included Japanese patients with IPF who started nintedanib between 31 August 2015 and 25 December 2018. The primary outcome was the frequency of adverse drug reactions (ADRs), defined as AEs for which a causal relationship with nintedanib could not be excluded. The secondary outcome was change from baseline in forced vital capacity (FVC). Outcomes were analysed in patients who stopped ('discontinued' subgroup) and continued ('continued' subgroup) nintedanib after 12 months. A multivariate analysis was performed to determine potential risk factors for treatment discontinuation.ResultsOf 5578 patients in the safety analysis set, 2795 (50.1%) discontinued nintedanib within 12 months of treatment initiation. Overall, 3767 patients (67.5%) had ADRs, with 1356 (24.3%) discontinuing nintedanib because of an ADR. Among patients in the 'discontinued' subgroup (n = 2795), 1442 (51.6%) discontinued because of an ADR. The most common ADRs causing discontinuation within 3 and 12 months were hepatic function abnormal (n = 137/730; 18.8%) and diarrhoea (n = 190/1442; 13.2%), respectively. At 12 months, the decrease in FVC from baseline was smaller in the 'continued' versus the 'discontinued' subgroup (adjusted mean ± standard error change - 104.4 ± 10.9 ml vs. - 311.2 ± 29.2 ml). Stage III/IV IPF and FVC < 70% predicted at baseline were risk factors for early treatment discontinuation.ConclusionAbout 50% of Japanese patients with IPF discontinued nintedanib within the first year of treatment, with worse lung function being associated with an increased risk of early treatment discontinuation.Trial registrationClinicalTrials.gov: NCT02607722; European Union electronic register of Post-Authorisation Studies: EUPAS10891.

Project description:IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is characterised by progressive worsening of dyspnoea and lung function. Nintedanib treatment is recommended to slow IPF disease progression. The aim of this post-marketing surveillance (PMS) study was to evaluate the safety and effectiveness of nintedanib over 24 months in patients with IPF in a real-world setting in Japan.MethodsThis prospective, non-interventional, all-case PMS study of nintedanib included Japanese patients with IPF who started nintedanib between 7 October 2015 and 2 May 2023. The primary outcome was to determine the proportion of patients with adverse drug reactions (ADRs), and the secondary outcome was the adjusted absolute change from baseline in forced vital capacity (FVC) at 24 months.ResultsIn total, 5717 patients from 1013 institutions were included in the safety analysis (mean ± standard deviation age 71.7 ± 8.1 years, 78.1% male, 70.8% current or former smokers). Most patients (83.9%) had initiated nintedanib at a dose of 150 mg capsules twice daily. At 24 months, 2841 patients (64.8%) had discontinued nintedanib, mainly due to adverse events (44.0%), ADRs (24.1%) or insufficient effectiveness (5.7%). The most common ADRs were diarrhoea (35.5%), hepatic function abnormal (14.4%), decreased appetite (9.9%), liver disorders (7.8%) and nausea (5.8%). The adjusted absolute mean change in FVC from baseline to 24 months was - 212.3 mL (95% confidence interval - 235.3, - 189.3).ConclusionThis is the largest prospective study to investigate patients with IPF who were treated with nintedanib. The safety and effectiveness of nintedanib treatment in this real-world setting of Japanese patients with IPF was similar to that reported in previous studies. Nintedanib effectively slowed the progression of IPF. No new safety concerns were identified, and the need for appropriate management of hepatic disorders and diarrhoea (as per the approved product information) was confirmed.Study registrationClinicalTrials.gov (NCT02607722)/European Union electronic register of Post-Authorisation Studies (EUPAS10891).

Project description:Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. We sought to characterize the population of patients prescribed antifibrotics and determine the drug tolerability of these medications in the Northern hub of the Southwest of England regional ILD network. Methods: A retrospective analysis of all patients treated with antifibrotics between August 2012 and July 2017 was undertaken. Baseline characteristics including patient demographics and pulmonary physiology, in addition to drug tolerability and reasons for treatment cessation were collated. Data were compared using unpaired student's t-test, Chi-squared, Mann-Whitney rank sum or ANOVA as appropriate. Logistic regression analysis evaluated clinical characteristics associated with discontinuation of pirfenidone therapy. P < 0.05 was considered statistically significant. Findings: A total of 164 patients, all with consensus diagnoses of IPF, were identified. Of these, 70.1% (115/164) received pirfenidone as their initial therapy. Baseline age, gender and pulmonary physiology did not differ significantly between groups. Drug discontinuation occurred most commonly due to adverse drug reactions events (ADRs) for both pirfenidone [40.0% (46/115)] and nintedanib [16.3% (8/49)]. Anorexia, rash and gastrointestinal disturbance were reported most commonly as the reason for cessation of pirfenidone; anorexia, nausea and weight loss for nintedanib. Duration of therapy prior to discontinuation because of ADRs did not differ significantly between medication groups but patients with a baseline FVC < 65% predicted, had a significantly shorter duration of pirfenidone prior to discontinuation due to ADRs, compared to those with a FVC 65-80% predicted. Multivariate logistic regression did not identify any independent baseline characteristics that predicted discontinuation of pirfenidone therapy prior to 52 weeks. Implications: Idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib had comparable treatment emergent adverse event (TEAE) profiles in clinical practice to those reported in clinical trials. The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.

Dataset Information

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil.

Objective

Methods

Results

Conclusion

Publications

Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil.

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