Dataset Information

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study.

ABSTRACT:

Background

The 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.

Methods

MUC5B 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.

Results

We 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 DL_CO (diffuse lung capacity) at the IPF diagnosis were associated with survival.

Conclusion

Our 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.

SUBMITTER: Doubkova M

PROVIDER: S-EPMC8442489 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Two 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. METHODS:Outpatients 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). RESULTS:In 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. CONCLUSIONS:Patient 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 REGISTRATION:NCT03420235 .

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