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

• Published in: Arthritis research & therapy Vol. 24; no. 1; p. 19
• Main Authors: Kreuter, Michael, Del Galdo, Francesco, Miede, Corinna, Khanna, Dinesh, Wuyts, Wim A, Hummers, Laura K, Alves, Margarida, Schoof, Nils, Stock, Christian, Allanore, Yannick
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.01.2022; BioMed Central; BMC
• Subjects: Analysis; Arthritis; Biomarkers; Care and treatment; Clinical trials; Diagnosis; Disease Progression; Forced vital capacity; Hospital care; Hospitalisation; Hospitalization; Hospitals; Humans; Joint model; Lung; Lung diseases; Lung Diseases, Interstitial - drug therapy; Patients; Prevention; Pulmonary fibrosis; Pulmonary function tests; Risk factors; Scleroderma; Scleroderma (Disease); Scleroderma, Systemic - drug therapy; SENSCIS; Surrogate endpoint; Systemic scleroderma; Systemic sclerosis-associated interstitial lung disease; Variables; France; United States > US; SENSCIS; Joint model; Forced vital capacity; Surrogate endpoint; Hospitalisation; Systemic sclerosis-associated interstitial lung disease
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-021-02710-9

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. 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. 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®. 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. ClinicalTrials.gov NCT02597933 . Registered on 8 October 2015.