Dataset Information

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

ABSTRACT:

Background

Real-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 question

The 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 methods

Patients 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.

Results

During 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).

Interpretation

This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

SUBMITTER: Belhassen M

PROVIDER: S-EPMC8094468 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF.MethodsMUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients (n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals (n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment.ResultsWe confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56-40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68-43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13-0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival.ConclusionOur real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.

Project description:Background: Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist-physician collaborative management, for patients receiving pirfenidone. Methods: We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist-physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis. Results: In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08-0.96, p = 0.041] and predicted baseline forced vital capacity <60% (HR 2.13, 95% CI 1.17-3.85, p = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (p = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03-0.84, p = 0.027). Conclusions: We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.

Project description:BackgroundTwo antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of idiopathic pulmonary fibrosis (IPF). Although efficacy and adverse events have been well studied, little is known about patient experiences with these drugs. We aimed to systematically and quantitatively evaluate patient expectations, experiences, and satisfaction with nintedanib and pirfenidone. Furthermore, we assessed which factors were associated with overall patient satisfaction with medication.MethodsOutpatients with IPF prospectively completed the Patient Experiences and Satisfaction with Medication (PESaM) questionnaire before start, and after three and 6 months of antifibrotic treatment, as part of a randomized eHealth trial (NCT03420235). The PESaM questionnaire consists of an expectation module, a validated generic module evaluating patient experiences and satisfaction concerning the effectiveness, side-effects, and ease of use of a medication, and a disease-specific module about IPF. Satisfaction was scored on a scale from - 5 (very dissatisfied) to + 5 (very satisfied).ResultsIn total, 90 patients were included, of whom 43% used nintedanib and 57% pirfenidone. After 6 months, the mean overall score for satisfaction with medication was 2.1 (SD 1.9). No differences were found in experiences and satisfaction with medication, and the number and severity of side-effects between nintedanib and pirfenidone. Perceived effectiveness of medication was rated as significantly more important than side-effects and ease of use (p = 0.001). Expectations of patients regarding effectiveness were higher than experiences after 6 months. Self-reported experience with effectiveness was the main factor associated with overall medication satisfaction.ConclusionsPatient experiences and satisfaction with antifibrotic treatment were fairly positive, and similar for nintedanib and pirfenidone. Systematic evaluation of patient expectations, experiences, and satisfaction with medication could enhance shared-decision making and guide drug treatment decisions in the future.Trial registrationNCT03420235 .

Project description:BackgroundNintedanib is effective for treating idiopathic pulmonary fibrosis (IPF), but some patients may exhibit a suboptimal response and develop on-treatment acute exacerbation (AE-IPF), hepatic injury, or mortality. It remains unclear which patients are at risk for these adverse outcomes.MethodsWe analysed the demographic and clinical data, baseline plasma levels of Krebs von den Lungen-6 (KL-6) and surfactant protein A (SPA), and longitudinal clinical courses of a real-world cohort of IPF patients who received nintedanib ≥ 14 days between March 2017 and December 2020. Cox proportional-hazards regression, subdistribution hazards regression, and sensitivity analyses were performed to investigate the association between baseline predictors and AE-IPF, mortality, and nintedanib-related hepatic injury. The relationship between baseline predictors and pulmonary function decline was determined.ResultsFifty-seven patients were included, of whom 24 (42%) developed hepatic injury, 20 (35%) had AE-IPF, and 16 (28%) died on-treatment. A baseline plasma KL-6 level ≥ 2.5 ng/mL, and diffusion capacity for carbon monoxide (DLCO) < 55% predicted, were associated with increased risk of hepatic injury (adjusted hazard ratio [aHR] was 3.46; 95% CI 1.13-10.60; p = 0.029 for KL-6, and 6.05; 95% CI 1.89-19.32; p = 0.002 for DLCO). Both factors also predicted severe and recurrent hepatic injury. Patients with baseline KL-6 ≥ 2.5 ng/mL also had a higher risk of AE-IPF (aHR 4.52; 95% CI 1.63-12.55; p = 0.004). For on-treatment mortality, baseline KL-6 ≥ 3.5 ng/mL and SPA ≥ 600 pg/mL were significant predictors (aHR 5.39; 95% CI 1.16-24.97; p = 0.031 for KL-6, and aHR 12.28; 95% CI 2.06-73.05; p = 0.006 for SPA). Results from subdistribution hazard regression and sensitivity analyses supported these findings. Patients with elevated baseline plasma KL-6 levels also exhibited a trend towards faster pulmonary function decline.ConclusionsFor patients with IPF who are receiving nintedanib, we have identified baseline predictors, in particular plasma KL-6 levels, for the risk of adverse outcomes. Patients with these predictors may require close monitoring for unfavourable responses during treatment. Our findings also support the prognostic role of molecular markers like KL-6 and may contribute to future formulation of more individualized therapeutic strategies for IPF.