Nintedanib In Idiopathic Pulmonary Fibrosis Research Articles

Real-world safety and effectiveness of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Multiple randomized controlled studies have shown that pirfenidone and nintedanib are effective and safe for treating idiopathic pulmonary fibrosis. This study aimed to evaluate their efficacy, safety, and tolerability in a real-world setting. We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases for real-world studies published up to March 3, 2023, on pirfenidone and nintedanib for idiopathic pulmonary fibrosis. A total of 74 studies with 23,119 participants were included. After 12months of treatment, the change from baseline in percent predicted FVC (%FVC) was - 0.75% for pirfenidone and - 1.43% for nintedanib. The change from baseline in percent predicted DLCO (%DCLO) was - 2.32% for pirfenidone and - 3.95% for nintedanib. The incidence of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) was 12.5% for pirfenidone and 14.4% for nintedanib. The IPF-related mortality rates of pirfenidone and nintedanib were 13.4% and 7.2%, respectively. The all-cause mortality was 20.1% for pirfenidone and 16.6% for nintedanib. In the pirfenidone group, 16.6% of patients discontinued treatment because of adverse events, and in the nintedanib group, 16.2% of patients discontinued treatment because of adverse events. The incidence of adverse events was 56.4% and 69.7% for pirfenidone and nintedanib, respectively. The results of this study indicate that pirfenidone and nintedanib are both effective in slowing down the decline of lung function in IPF patients in real-world settings. The incidence of adverse events with pirfenidone is lower than that with nintedanib, but both are below the clinical trial data, and no new major adverse events have been observed. The discontinuation rates due to adverse reactions of the two drugs are consistent with clinical trial data, indicating good tolerability. However, the mortality rates and AE-IPF incidence rates of these two drugs in real-world settings are higher than those in previous clinical trials, with pirfenidone patients showing a higher mortality rate. Further large-sample studies are needed to investigate the risks of these drugs in these aspects. Additionally, we recommend that future real-world studies pay more attention to patients' subjective symptoms and conduct stratified analyses of the efficacy and safety of pirfenidone and nintedanib based on factors such as patients' baseline lung function, comorbidities, and age, in order to provide more personalized medication advice for IPF patients in clinical practice.

Patient Profile-Based Management with Nintedanib in Patients with Idiopathic Pulmonary Fibrosis.

A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations.

Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease (p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 (p = 0.039) and for DLCO (p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.

Healthcare resource use and associated costs in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis

BackgroundReal-world data regarding health-care resource use (HCRU) and costs of idiopathic pulmonary fibrosis (IPF) are scarce. In France, at the time of the study, pirfenidone and nintedanib were reimbursed for documented IPF only, with similar reimbursement criteria with regard to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in a multidisciplinary setting. The objective of this study was to evaluate costs related to HCRU in patients newly treated with pirfenidone or nintedanib in 2015–2016, in France, using the exhaustive claims data of the French National Health System. MethodsPatients aged <50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. HCRU-related costs up to 31 December 2017 were compared using generalized linear models adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. ResultsDuring the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical visits prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with higher costs for medications (1.2; 95% CI, 1.1–1.3) and medical visits (1.3; 95% CI, 1.2–1.4), as well as a higher global cost (1.1; 95% CI, 1.0–1.2). The costs of medical procedures, hospitalizations and indirect HCRU did not statistically differ between the two cohorts. ConclusionsThis observational study identified potential differences in HCRU-related costs under newly prescribed antifibrotic drugs, deserving further explorations.

Nintedanib in IPF: Post hoc Analysis of the Italian FIBRONET Observational Study

Background: The FIBRONET study was an observational study of patients with idiopathic pulmonary fibrosis (IPF) in Italy. Objectives: In this post hoc descriptive analysis, we describe changes in lung function, anxiety/depression, coughing, exacerbations, and adverse events (AEs) in patients receiving nintedanib treatment. Methods: Patients with IPF from 20 centers in Italy, aged ≥40 years who received nintedanib for ≥7 months, were followed up for 12 months from study enrollment, attending clinic visits every 3 months. Outcomes included change in forced vital capacity (FVC)% predicted from baseline to 12 months, anxiety/depression measured by the Hospital Anxiety and Depression Scale (HADS), and the proportion of patients with cough, AEs, and exacerbations. Results: In total, 52 patients received nintedanib (mean duration of 11.6 months). Ten patients had dose reductions from 150 mg to 100 mg twice daily, due to AEs. FVC% predicted was unchanged in the overall nintedanib population (78.7% at baseline; 79.8% at 12 months) and those with a reduced dose (77.7% at baseline; 81.0% at 12 months). HADS score was low at baseline and throughout the study. The proportion of patients with cough decreased from 50.0% to 21.2% over 12 months. Two patients experienced exacerbations, 2 patients discontinued treatment, and 27 (51.9%) reported AEs. The most common AE was diarrhea (34.6%). Conclusions: In patients with IPF who received nintedanib in the FIBRONET study, FVC% predicted was stable over 12 months, and the proportion of patients with cough decreased. The safety profile was consistent with the known safety profile for nintedanib in IPF.

Real world efficacy and safety of nintedanib in idiopathic pulmonary fibrosis: A single center, observational study from India.

Background:Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis (IPF) has been established by multiple clinical trials. This study aims to assess the efficacy and safety of nintedanib in real-world IPF patients in India.Methods:Clinical records of IPF patients (prescribed with nintedanib) visiting tertiary pulmonary care center, between June 2016 and December 2019, were analyzed retrospectively. Data were analyzed for forced vital capacity (FVC), Diffusing capacity of lung for carbon monoxide(DLCO), 6-min walk distance (6-MWD). Acute exacerbations and adverse events were also analyzed.Results:A total of 76 IPF patients were prescribed with nintedanib. Drug was prescribed at 100 and 150 mg BD dose to 37 and 39 patients. Ten patients (13.1%), of which eight were over the age of 60 years, died during the study period. Only 42 patients visited for follow-up. Mean baseline FVC was 1.67 L and mean annualized absolute change in FVC and FVC % predicted was −0.07 L and −1.80%, respectively. Mean baseline DLCO was 37.21% and mean annualized absolute change in DLCO % predicted was-2.20%. At follow-up, 1 (2.38%), 17 (40.47%), and 24 (57.14%) patients were at Deparatment of Internal Medicine stage I, II, and III, respectively. Acute exacerbations and adverse events were reported by 48 and 6 patients, respectively.Conclusion:Our results support the findings from previous studies, that nintedanib leads to annual decline in parameters such as FVC and DLCO and increased 6-MWD. It was found to be well tolerated in the Indian patients with IPF.

P16‐86: Tolerability and safety of nintedanib for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases

P16‐86: Tolerability and safety of nintedanib for idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases

O25‐4: A real‐world study of the safety and efficacy of low‐dose nintedanib for idiopathic pulmonary fibrosis

O25‐4: A real‐world study of the safety and efficacy of low‐dose nintedanib for idiopathic pulmonary fibrosis

Protocol for long-term effect of pulmonary rehabilitation under nintedanib in idiopathic pulmonary fibrosis.

BackgroundPulmonary rehabilitation causes short-term improvement in exercise capacity, dyspnoea and health-related quality of life in idiopathic pulmonary fibrosis (IPF); however, long-term maintenance of the improvement is difficult. Nintedanib, an antifibrotic drug, has been shown to delay the worsening of pulmonary function in IPF. Therefore, the concomitant use of nintedanib with pulmonary rehabilitation is anticipated to contribute to the long-term maintenance of the pulmonary rehabilitation effects. The long-term effect of pulmonary rehabilitation under nintedanib treatment in IPF (FITNESS) study is a multicenter, randomised, prospective, parallel-group, open-label trial.MethodsThe study will enrol 84 patients with IPF who have been treated with nintedanib. Patients in the pulmonary rehabilitation group will receive a programmed short-term induction pulmonary rehabilitation programme, followed by a maintenance home-based pulmonary rehabilitation programme, while patients in the control group will receive usual outpatient care. Patients in both groups will continue to receive nintedanib treatment throughout the study period. The primary end-point of the study is to compare the change in the 6-min walk distance from the baseline to 12 months between the pulmonary rehabilitation and control groups. The main secondary end-point is endurance exercise time, measured using a bicycle ergometer.DiscussionFITNESS is the first randomised controlled study to evaluate the long-term effects of pulmonary rehabilitation in IPF treated with nintedanib. This study will address the hypothesis that concomitant use of nintedanib contributes to the maintenance of long-term effects of pulmonary rehabilitation, thus leading to a comprehensive therapeutic approach of “nintedanib and pulmonary rehabilitation” in the antifibrotic era.

Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan.

Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited. The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records. Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax). Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.

Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis

BackgroundReal-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion.Research questionThe data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015–2016.Study design and methodsPatients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period.ResultsDuring the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3–2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0–1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6–0.9).InterpretationThis observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

Clinical Significance of Continuable Treatment with Nintedanib Over 12 Months for Idiopathic Pulmonary Fibrosis in a Real-World Setting.

PurposeThe INPULSIS-ON study suggested the safety and tolerability of long-term nintedanib treatment for idiopathic pulmonary fibrosis (IPF). However, there are no real-world studies on long-term nintedanib treatment. The main aim of the study was to investigate the efficacy and the tolerability of long-term treatment with nintedanib for IPF in clinical practice.Patients and MethodsThis retrospective study enrolled 104 IPF patients who underwent treatment with nintedanib. Among these patients, 51 were able to receive nintedanib for more than 12 months (ie, treatment with nintedanib over 12 months was possible [P group]) and 53 were not able to receive nintedanib for more than 12 months (ie, treatment with nintedanib over 12 months was impossible [I group]). The tolerability and efficacy of nintedanib were compared between the two groups.ResultsIn the I group, 29 patients were unable to continue nintedanib therapy because of adverse effects, including diarrhea and nausea/anorexia. In addition, 19 and four patients could not continue nintedanib treatment because of IPF progression and worsening of performance status (PS), respectively. One patient suddenly died during nintedanib treatment. The incidence of nausea/anorexia in the I group was significantly higher than in the P group (49.06 vs 25.49%). The survival time was significantly longer in the P group than in the I group (35 vs 12 months). The decline in forced vital capacity was significantly larger in the I group than in the P group (165 vs 10 mL/year). Poor PS at nintedanib initiation was the only significant risk factor for nintedanib treatment discontinuation over 12 months. Finally, the survival time was significantly longer in patients with good PS than in those with poor PS (27 vs 13 months).ConclusionPoor PS can result in discontinuation of nintedanib after 12 months. Long-term nintedanib treatment may be effective for survival.

Progressive fibrosing interstitial lung diseases: A new concept and indication of nintedanib

Many interstitial lung diseases (ILDs) are characterized by chronic progressive fibrosis. The antifibrotic agents may prevent disease progression of these diseases. Nintedanib is a triple tyrosine kinase inhibitor and has an antifibrotic effect. The proven beneficial effects of nintedanib in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc)-associated ILD, nintedanib was intended for use in many other fibrotic lung diseases consistent with the concept described below. With this trial, the concept and definition of progressive fibrosing ILD (PF-ILD) were created, a type of fibrosing diseases that progresses with fibrosis measured in forced vital capacity and high-resolution CT findings and worsening of respiratory symptoms at a certain rate or faster. PF-ILDs are composed of idiopathic interstial pneumonias such as non-specific interstitial pneumonia and unclassifiable interstitial pneumonia and inhalation lung diseases such as chronic hypersensitivity pneumonia and connective tissue disease-associated ILD such as rheumatoid arthritis-related ILD and SSc-related ILD and sarcoidosis and so on. Nintedanib significantly reduced the annual rate of decline in forced vital capacity over 52 weeks compared with placebo. Nintedanib received marketing approval in the United States and Japan for the treatment of PF-ILDs. This review summarizes the new concept of PF-ILDs and effectiveness of nintedanib to PF-ILDs and discussion points to be solved in the future when using nintedanib for PF-ILDs.

THE CASE OF ASCENDING PARAPARESIS FOLLOWING NINTEDANIB

SESSION TITLE: Fellows Diffuse Lung Disease SESSION TYPE: Fellow Case Reports PRESENTED ON: October 18-21, 2020 INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an incurable, progressive fibrosing interstitial lung disease reflected by a decline in lung function, worsening dyspnea, exercise capacity, and overall poor prognosis. Nintedanib is one of two anti-fibrotic therapies approved for the treatment of IPF. We present the case of a patient who presented with ascending paraparesis following Nintedanib and here by hope to shed light on treatment of IPF and potential but unproven side effects of Nintedanib. CASE PRESENTATION: 39-year-old male with history of familial IPF secondary to short telomere syndrome who presented with bilateral progressive upper and lower extremity paresthesia and weakness which started shortly after he was commenced on Nintedanib for pulmonary fibrosis. This progressed to numbness and weakness till he could barely walk or lift his arms against gravity by day 5. He denied any preceding upper respiratory tract or gastrointestinal symptoms. Physical exam was significant for bibasilar fine velcro crackles in the lungs, hyporeflexia and flaccid tone with power of 3/5 in all extremities. He had negative autoimmune work up. Cerebro-spinal fluid analysis, Pan spinal MRI and MRI of the brain were unrevealing. Electromyogram was significant for motor polyneuropathy with limited demyelinating features. Management was mainly supportive with physical therapy and patient gradually regained his strength back to baseline. DISCUSSION: Nintedanib inhibits multiple tyrosine kinases and targets growth factors like vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor which have been implicated in the pathogenesis of idiopathic pulmonary fibrosis. It is important to monitor potential adverse effects aside from what was noted in the relevant trials of which diarrhea was the commonest. Other side effects were bronchitis, upper respiratory tract symptoms, nausea, vomiting, cough weight loss and back ache. Our patient presented with paresthesias and ascending paresis after taking Nintadenib. He had negative extensive work up for other causes of ascending paralysis and his weakness gradually improved after stopping the medication and with Physical therapy. He was initially offered Intravenous immunoglobulin but was already improving clinically with supportive therapy and physical therapy, so after weighing risk to benefit, decided against it. CONCLUSIONS: With the widening use of Nintedanib, more patients will undoubtedly be exposed to it, and providers should be aware of this unlikely, but serious, potential side effect of Guillain-Barre like presentation which has been associated with other tyrosine kinase inhibitors. To the best of our knowledge, this is the first reported case of ascending paresis following the use of Nintedanib in particular. Reference #1: Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis. (2015). New England Journal Of Medicine, 373(8), 782-782. doi: 10.1056/nejmx150012 Reference #2: "Human Medicines European Public Assessment Report (EPAR): Ofev, Nintedanib, Idiopathic Pulmonary Fibrosis, Date Of Authorisation: 14/01/2015, Revision: 10, Status: Authorised". 2019. Case Journals, doi:10.31525/cmr-587247. Reference #3: Lehky, T. J. et al. "Neuromuscular Junction Toxicity With Tandutinib Induces A Myasthenic-Like Syndrome". Neurology, vol 76, no. 3, 2011, pp. 236-241. Ovid Technologies (Wolters Kluwer Health), doi:10.1212/wnl.0b013e3182074a69. DISCLOSURES: No relevant relationships by Shehabaldin Alqalyoobi, source=Web Response No relevant relationships by Afua Kunadu, source=Web Response No relevant relationships by Ogugua Obi, source=Web Response

Healthcare use and costs among Medicare enrollees on pirfenidone versus nintedanib for idiopathic pulmonary fibrosis.

Aim: Compare healthcare utilization and costs between Medicare beneficiaries with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone or nintedanib. Methods: Retrospective cohort study of Medicare beneficiaries (100% Research Identifiable Files) with IPF who initiated pirfenidone or nintedanib between 15 October2014 and31 December2015. Inverse probability of treatment weighting using propensity scores adjusted for baseline covariates. Outcomes: hospitalization and monthly costs. Results: Hazard and incidence rate ratios (95% CI) for all-cause (0.79 [0.68-0.91]; 0.69 [0.59-0.82]) and respiratory-related (0.80 [0.65-0.97]; 0.71 [0.57-0.90]) hospitalizations favored pirfenidone versus nintedanib. Monthly inpatient costs were lower for pirfenidone versus nintedanib patients; outpatient and pharmacy costs were similar. Conclusion: In patients with IPF, pirfenidone compared with nintedanib has a moderate but significant protective effect on hospitalization, corresponding to lower inpatient costs.

Anticoagulant Use and Bleeding Risk in Central European Patients with Idiopathic Pulmonary Fibrosis (IPF) Treated with Antifibrotic Therapy: Real-World Data from EMPIRE.

IntroductionNintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF).ObjectiveOur objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy.MethodsThe European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized.ResultsGroup A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively).ConclusionReal-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).Electronic supplementary materialThe online version of this article (10.1007/s40264-020-00978-5) contains supplementary material, which is available to authorized users.

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry

BackgroundPragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection.MethodsData from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation.Results703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent.ConclusionsThis analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: a retrospective, observational, cohort study.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018.We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (DLCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and DLCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; DLCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event.This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF.

Nintedanib in idiopathic pulmonary fibrosis: benefits at lower cost

Nintedanib in idiopathic pulmonary fibrosis: benefits at lower cost

AUTOIMMUNITY TRIGGERED BY IMMUNOTHERAPY: A CASE OF AUTOIMMUNE HEPATITIS-INDUCED BY NINTEDANIB TREATMENT FOR IPF

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive loss of lung function, dyspnea and impairment in quality of life.1 Nintedanib is a tyrosine kinase inhibitor approved for treatment of IPF which can reduce the annual rate of decline in forced vital capacity.2 Nintedanib’s adverse effects are managed symptomatically, by dose reduction or treatment interruption.3 We present a case of drug induced autoimmune hepatitis associated with Nintedanib. CASE PRESENTATION: A 59-year-old male with 19 pack year smoking history, COPD GOLD group B, GERD and CAD who initially presented to his PCP 2 years prior with dyspnea. Patient underwent CABG and bio-prosthetic aortic valve replacement, but dyspnea persisted. PFTs showed a restrictive pattern and reduced DLCO. Chest CT showed mild centrilobular emphysema, coarse interstitial markings and bilateral pleural-parenchymal scarring with early honeycombing in the lung bases, highly suggestive of pulmonary fibrosis. Workup for secondary causes of fibrotic lung disease including connective tissue diseases and barium swallow test were negative. He was diagnosed with IPF and was started on Nintedanib within a month. Pretreatment liver function tests (LFTs) were normal. Three months into treatment, Nintedanib was discontinued due severe nausea, vomiting and diarrhea. LFTs at this time were significant for ALP 471, AST 139 and ALT 189. Liver ultrasound showed fatty infiltration and chronic liver disease workup was negative except for gamma-globulin elevation. Repeat LFTs 4 weeks after stopping Nintedanib were persistently elevated while liver biopsy showed active lobular, portal hepatitis and mild focal fibrosis. Patient was diagnosed with drug-induced autoimmune hepatitis and started on Prednisone which led to normalization of liver enzymes. Liver panel worsened when prednisone was tapered, and therefore Azathioprine was started as a steroid sparing agent. Patient continues to be on Prednisone and Azathioprine and is undergoing workup for lung transplant. LFTs improved to normal limits on current treatment. DISCUSSION: Hepatitis is a potential complication associated with Nintedanib use 4. Mechanism of hepatocellular injury remains unclear but is thought to be due to epidemiologic variances in tolerability.5 Current recommendations are to monitor LFTs every 3 months while on Nintedanib. CONCLUSIONS: A literature review did not yield other cases of Nintedanib causing drug induced autoimmune hepatitis. Nintedanib’s adverse events are still not well known, making the documentation of cases such as this one important to aid in the monitoring of patients undergoing therapy. Reference #1: Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824.https://doi.org/10.1164/rccm.2009-040G. Reference #2: Richeldi L , Cottin V , du Bois RM , et al . Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med 2016;:74–9.https://doi.org/10.1016/j.rmed.2016.02.001 Reference #3: Richeldi L , du Bois RM , Raghu G , et al . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014 2071;370 82:2071–82.https://doi.org/10.1056/NEJMoa1402584 DISCLOSURES: Speaker/Speaker's Bureau relationship with boehringer ingleheim Please note: $20001 - $100000 Added 03/13/2019 by Tariq Cheema, source=Web Response, value=Honoraria No relevant relationships by Muhammad Asad Faruqi, source=Web Response No relevant relationships by Ayla Gordon, source=Web Response No relevant relationships by Melissa Mosley, source=Web Response No relevant relationships by Erica Rabold, source=Web Response