Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Glaspole, Ian; Bonella, Francesco; Bargagli, Elena; Glassberg, Marilyn K.; Caro, Fabián; Stansen, Wibke; Quaresma, Manuel; Orsatti, Leticia; Bendstrup, Elisabeth

doi:10.1186/s12931-021-01695-y

Cited by 22 publications

(28 citation statements)

References 25 publications

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“…In IPF and cHP, several studies have shown an association between mortality and the burden of comorbidities, expressed either as numbers, frequencies, or using the Charlson comorbidity index [ 2 , 3 , 22 ]. This was not the case in our study.…”

Section: Discussionmentioning

confidence: 99%

Comorbidities in unclassifiable interstitial lung disease

et al. 2022

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Background Comorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival. Methods Incident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps. Results A total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters. Conclusions The comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.

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Section: Discussionmentioning

confidence: 99%

Comorbidities in unclassifiable interstitial lung disease

et al. 2022

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“…81 They showed that the efficacy of nintedanib on FVC decline was consistent regardless of comorbidities or age, but the rate of drug discontinuation was markedly higher in patients over 75 years and with more comorbidities. 81 Justet et al addressed antifibrotic safety in patents with TRG mutations, demonstrating that both pirfenidone and nintedanib appeared safe in a cohort of 89 patients and reduced FVC decline. 82 Many studies have examined the role of N-acetylcysteine in specific clusters of patients with IPF.…”

Section: Antifibrotics In Fibrosing Ildsmentioning

confidence: 99%

“…They identified that patients with advanced IPF did not demonstrate more rapid lung function decline but did have higher mortality, indicating that prospective studies in high‐risk groups are required. Glaspole et al assessed the efficacy of nintedanib in patients with IPF who were elderly and had multiple comorbidities from pooled data of five separate clinic trials 81 . They showed that the efficacy of nintedanib on FVC decline was consistent regardless of comorbidities or age, but the rate of drug discontinuation was markedly higher in patients over 75 years and with more comorbidities 81 .…”

Section: Therapeutic Advances In Ildmentioning

confidence: 99%

“…Glaspole et al assessed the efficacy of nintedanib in patients with IPF who were elderly and had multiple comorbidities from pooled data of five separate clinic trials 81 . They showed that the efficacy of nintedanib on FVC decline was consistent regardless of comorbidities or age, but the rate of drug discontinuation was markedly higher in patients over 75 years and with more comorbidities 81 . Justet et al addressed antifibrotic safety in patents with TRG mutations, demonstrating that both pirfenidone and nintedanib appeared safe in a cohort of 89 patients and reduced FVC decline 82 …”

Section: Therapeutic Advances In Ildmentioning

confidence: 99%

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Contemporary Concise Review 2021: Interstitial lung disease

McCarthy

Keane

2022

Respirology

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The last 2 years have presented previously unforeseen challenges in pulmonary medicine. Despite the significant impact of the SARS-CoV-2 pandemic on patients, clinicians and communities, advances in the care and understanding of interstitial lung disease (ILD) continued unabated. Recent studies have led to improved guidelines, better understanding of the role for antifibrotics in fibrosing ILDs, prognostic indicators and novel biomarkers. In this concise contemporary review, we summarize many of the important studies published in 2021, highlighting their relevance and impact to the management and knowledge of ILD.

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“…Several physiological [ 9 , 10 ] and radiological measures, such as forced vital capacity (FVC) diffusion capacity of the lung for carbon monoxide (DLco), traction bronchiectasis, and honeycombing have been reported as useful predictors of IPF mortality [ 11 , 12 ]. IPF has a variable clinical course, which ranges from asymptomatic to severe irreversible respiratory failure along with acute exacerbation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Radiological and Physiological Predictors of IPF Mortality

et al. 2021

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Background and Objectives: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images, including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53–85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3–35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47, and 1615 ± 1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ± 13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9th rib was 26.4 ± 8.8 mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months (0.9–142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912, 95% confidence interval (CI): 0.859–0.979, p-value: 0.009] and percent FRC [HR: 0.980, 95% CI: 0.967–0.992, p-value: 0.002] were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibrotic agents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

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Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Cited by 22 publications

References 25 publications

Comorbidities in unclassifiable interstitial lung disease

Comorbidities in unclassifiable interstitial lung disease

Contemporary Concise Review 2021: Interstitial lung disease

Radiological and Physiological Predictors of IPF Mortality

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