Treatment and Systemic Sclerosis Interstitial Lung Disease Outcome: The Overweight Paradox

Nagy, Alexandra; Palmer, Erik; Polivka, Lőrinc; Eszes, Noémi; Vincze, Krisztina; Bárczi, Enikő; Bohács, Anikó; Tárnoki, Ádám Domonkos; Tárnoki, Dávid László; Nagy, György; Kiss, Emese; Maurovich-Horvat, Pál; Müller, Veronika

doi:10.3390/biomedicines10020434

Cited by 6 publications

(6 citation statements)

References 47 publications

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“…Our finding that the rate of decline in FVC was greatest in subjects with baseline BMI < 25 kg/m 2 is consistent with observations in subjects with IPF in the INPUL-SIS trials [10] and other studies in subjects with IPF and systemic sclerosis-associated ILD [13,14]. In an analysis including data from trials of pirfenidone in patients with IPF, the annualized decline in FVC % predicted was greater in patients with baseline BMI < 25 kg/m 2 than BMI ≥ 25 to < 30 or ≥ 30 kg/m 2 in the placebo groups, but this was not observed in patients who received pirfenidone [13].…”

Section: Discussionsupporting

confidence: 91%

“…Published data on the association between weight and outcomes in patients with pulmonary fibrosis are conflicting. While some studies have suggested that lower body mass index (BMI) is associated with worse outcomes [7][8][9][10][11][12][13][14], others have found no significant association [2,5,[15][16][17]. Weight loss has been associated with worse outcomes in patients with pulmonary fibrosis [5,7,9,10,13,[18][19][20][21], although among overweight and obese patients, intentional weight loss may improve lung function [22,23].…”

Section: Introductionmentioning

confidence: 99%

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Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

et al. 2023

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Background Lower body mass index (BMI) and weight loss have been associated with worse outcomes in some studies in patients with pulmonary fibrosis. We analyzed outcomes in subgroups by BMI at baseline and associations between weight change and outcomes in subjects with progressive pulmonary fibrosis (PPF) in the INBUILD trial. Methods Subjects with PPF other than idiopathic pulmonary fibrosis were randomized to receive nintedanib or placebo. In subgroups by BMI at baseline (< 25, ≥ 25 to < 30, ≥ 30 kg/m2), we analyzed the rate of decline in FVC (mL/year) over 52 weeks and time-to-event endpoints indicating disease progression over the whole trial. We used a joint modelling approach to assess associations between change in weight and the time-to-event endpoints. Results Among 662 subjects, 28.4%, 36.6% and 35.0% had BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively. The rate of decline in FVC over 52 weeks was numerically greater in subjects with baseline BMI < 25 than ≥ 25 to < 30 or ≥ 30 kg/m2 (nintedanib: − 123.4, − 83.3, − 46.9 mL/year, respectively; placebo: − 229.5; − 176.9; − 171.2 mL/year, respectively). No heterogeneity was detected in the effect of nintedanib on reducing the rate of FVC decline among these subgroups (interaction p = 0.83). In the placebo group, in subjects with baseline BMI < 25, ≥ 25 to < 30 and ≥ 30 kg/m2, respectively, 24.5%, 21.4% and 14.0% of subjects had an acute exacerbation or died, and 60.2%, 54.5% and 50.4% of subjects had ILD progression (absolute decline in FVC % predicted ≥ 10%) or died over the whole trial. The proportions of subjects with these events were similar or lower in subjects who received nintedanib versus placebo across the subgroups. Based on a joint modelling approach, over the whole trial, a 4 kg weight decrease corresponded to a 1.38-fold (95% CI 1.13, 1.68) increase in the risk of acute exacerbation or death. No association was detected between weight loss and the risk of ILD progression or the risk of ILD progression or death. Conclusions In patients with PPF, lower BMI at baseline and weight loss may be associated with worse outcomes and measures to prevent weight loss may be required. Trial registration:https://clinicaltrials.gov/ct2/show/NCT02999178.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

et al. 2023

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“…The limitations of our study were the retrospective single-center design and the low number of patients, which did not allow for a better stratification according to clinical features or treatment. Further prospective studies are needed to establish new markers of progression and to develop guidelines for the optimal timing of treatment introduction, with the adequate therapies being a combination of ISU and/or biological therapy and/or antifibrotics in the case of PPF in this special subgroup of SSc-ILD patients [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry

et al. 2022

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Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.

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“…Lower BMI, malnutrition, and changes in body composition are common features in SSc and are associated with disease duration, gastrointestinal involvement, and ILD. 27 – 29 Coherently with the short disease duration (<3 years) of the study cohort, BMI was mostly in the normality range; therefore, we can consider our patients a good proxy for ILO-naïve patients in the clinical practice. Our findings suggest that body composition and adipose tissue could play a role also in the pathogenesis and in the response to the treatment of SSc and that different bodyweight at the beginning of the disease could reflect different clinical phenotypes in patients with SSc.…”

Section: Discussionmentioning

confidence: 95%

Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis

Bixio

Adami

Bertoldo

et al. 2022

Therapeutic Advances in Musculoskeletal

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Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud’s phenomenon and digital ulcers. The suggested dose is 0.5–2 ng/kg/min for 6–8 h, and the maximum dose is decided upon the patient’s tolerance. Objectives: This study aims to analyze ILO infusion tolerance and possible predictive factors in patients with SSc. Design: This is a retrospective observational study. Method: We evaluated 113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the incidence of adverse events (AEs), and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical and employed generalized linear models to assess possible predictors of maximum tolerated ILO infusion rate and AEs and logistic regression to assess predictors of AEs. Results: The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate ( β = −0.21, p = 0.02) after correction for relevant confounding factors. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence interval (CI) = 2.359–82.845]. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the patients at least once. Conclusion: This study showed that higher BMI was statistically associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO regimens still need to be tailored to the patient. Plain Language Summary Introduction: Systemic sclerosis is a rare a rheumatic disease characterized by skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs involvement. Iloprost, which is administered as intravenous infusion, is one of the main treatments for this disease, and it is effective in reducing vasospasm and the frequency of DUs. Even if there is a suggested dose range, the exact dose must be tailored on each patient, because the tolerance to the drug is variable. Tolerance is limited by dose-dependent unwanted effects, as headache, low blood pressure, dizziness, and sickness. This study aimed to identify possible predictors of such tolerance. Materials and Methods: We collected data from our patients with systemic sclerosis beginning the treatment with iloprost between January 2004 and November 2021 at our hospital facility in Verona, Italy, and analyzed different factors that could be associated with a better tolerance, as age, sex, disease duration, smoking habit, body mass index (a measure of body fatness), blood pressure, concomitant medications, and different patterns of the disease. Results: We found that a higher body mass index was associated with lower iloprost tolerance and higher adverse events rate in patients with systemic sclerosis, while we did not find a correlation with other factors. We believe overweight and obese patients (who have a higher body mass index) have a defect in the vasodilatation mechanism and can therefore be more susceptible to the effect of this medication. Conclusions: While preliminary, our results could provide a good starting point to develop a predictive tool to limit adverse events during this therapy.

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Treatment and Systemic Sclerosis Interstitial Lung Disease Outcome: The Overweight Paradox

Cited by 6 publications

References 47 publications

Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

Weight loss and outcomes in subjects with progressive pulmonary fibrosis: data from the INBUILD trial

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry

Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis

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