A decline in forced vital capacity (FVC) has a clinically relevant association with the risk for all-cause and systemic sclerosis (SSc)-linked hospitalization or death in patients with SSc interstitial lung disease (SSc-ILD), according to study results published in Arthritis Research & Therapy.
Researchers sought to explore the association between lung function decline and hospitalization events in patients with SSc-ILD.
Data from the phase 3 SENSCIS® trial (ClinicalTrials.gov Identifier: NCT02597933) – a large, randomized, placebo-controlled, parallel study analyzing the safety and efficacy of nintedanib in patients with SSc-ILD – were used to conduct a joint model analysis.
Researchers used joint models for longitudinal and time-to-event data to evaluate the association between rate of decline in FVC% predicted and hospitalization-related endpoints (ie, time to first all-cause hospitalization or death; time to first SSc-related hospitalization or death; and time to first admission to an emergency department [ED] or a hospital, followed by admission to an intensive care unit [ICU] or death) during the treatment period. Patients with SSc-ILD were followed-up with for 52 weeks.
Of the 576 participants enrolled in the SENSCIS trial who received 1 or more doses of nintedanib or placebo, FVC and hospitalization data were available for 574. Overall, 75.1% of the patients were women. The mean FVC% predicted at baseline was 72.5±16.7 in the total population; 72.0±16.4 and 70.5±18.7 in participants with all-cause and SSc-related hospitalization events or death, respectively; and 70.9±16.7 in patients with ED or hospital admission, followed by admission to an ICU or death. Among patients who received treatment with nintedanib and placebo in the SENSCIS trial, the annual rate of decline in FVC% predicted was -1.4±0.4% and -2.6±0.4% for nintedanib and placebo, respectively.
At 52 weeks, a statistically significant association was observed between FVC decline and risk for all-cause (n=78) and SSc-related (n=42) hospitalizations or death (P <.0001 for both). A reduction of 3% in FVC was associated with a 1.43-fold increased risk for all-cause hospitalization or death (hazard ratio [HR], 1.43; 95% CI, 1.24-1.65; P <.0001) and a 1.48-fold increased risk for SSc-related hospitalization or death (95% CI, 1.23-1.77; P <.0001). No significant association was observed between FVC decline and ED admission, and between FVC and hospital admission followed by ICU admission or death, at 52 weeks and during the entire trial period (P =.1549 and P =.3376, respectively).
Study limitations included the fact that the analysis was limited to data collected in the SENSCIS trial only; many participants with SSc-ILD were receiving immunosuppressive therapy that could have had an impact on ILD progression rate and increased the risk for infections; and that the results may not be generalizable to the entire SSc-ILD population.
However, the researchers noted that the findings from the study provided evidence that a decline in FVC may be used as a surrogate endpoint for time to first hospitalization, though additional validation was needed.
They concluded, “Slowing FVC decline may prevent [hospitalizations] in patients with SSc-ILD and supports the value of serial FVC measurement in [randomized] controlled trials.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kreuter M, Del Galdo F, Miede C, et al. Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis. Arthritis Res Ther. 2022;24(1):19. doi:10.1186/s13075-021-02710-9