Dataset Information

Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis.

ABSTRACT:

Background

Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.

Methods

We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.

Results

There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.

Conclusions

The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.

Trial registration

ClinicalTrials.gov NCT02597933 . Registered on 8 October 2015.

SUBMITTER: Kreuter M

PROVIDER: S-EPMC8751320 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:This study was designed (a) to evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CaM) system in patients with systemic sclerosis (SSc),-related interstitial lung disease (SSc-ILD), (b) to investigate the relationship between physiologic parameters (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]), patient-centred measures of dyspnea and functional disability and CaM and visual reader-based (CoVR) methods, and (c) to identify potential surrogate measures from quantitative and visual HRCT measurement. METHODS:126 patients with SSc underwent chest radiography, HRCT and PFTs. The following patient-centred measures were obtained: modified Borg Dyspnea Index (Borg score), VAS for breathing, and Health Assessment Questionnaire-Disability Index (HAQ-DI). HRCT abnormalities were scored according to the conventional visual reader-based score (CoVR) and by a CaM. The relationships among the HRCT scores, physiologic parameters (FVC and DLCO, % predicted) results and patient-centred measures, were calculated using linear regression analysis and Pearson's correlation. Multivariate regression models were performed to identify the predictor variables on severity of pulmonary fibrosis. RESULTS:Subjects with limited cutaneous SSc had lower HAQ-DI scores than subjects with diffuse cutaneous SSc (p <0.001). CaM and CoVR scores were similar in the 2 groups. In univariate analysis, a strong correlation between CaM and CoVR was observed (p <0.0001). In multivariate analysis the CaM and CoVR scores were predicted by DLco, FVC, Borg score and HAQ-DI. Age, sex, disease duration, anti-topoisomerase antibodies and mRSS were not significantly associated with severity of pulmonary fibrosis on CaM- and CoVR methods. CONCLUSIONS:Although a close correlation between CaM score results and CoVR total score was found, CaM analysis showed a more significant correlation with DLco (more so than the FVC), patient-centred measures of perceived dyspnea and functional disability. Computer-aided tomographic analysis is computationally efficient, and in combination with physiologic and patient-centred measures, it could allow a means for accurately assessing and monitoring the disease progression or response to therapy.