Cohort Enrichment Strategies for Progressive Interstitial Lung Disease in Systemic Sclerosis From European Scleroderma Trials and Research

TY - JOUR

T1 - Cohort Enrichment Strategies for Progressive Interstitial Lung Disease in Systemic Sclerosis From European Scleroderma Trials and Research

AU - Hoffmann-Vold, Anna-Maria

AU - Brunborg, Cathrine

AU - Airò, Paolo

AU - Ananyeva, Lidia P

AU - Czirják, László

AU - Guiducci, Serena

AU - Hachulla, Eric

AU - Li, Mengtao

AU - Mihai, Carina

AU - Riemekasten, Gabriela

AU - Sfikakis, Petros P

AU - Valentini, Gabriele

AU - Kowal-Bielecka, Otylia

AU - Allanore, Yannick

AU - Distler, Oliver

AU - EUSTAR Collaborators

AU - Kötter, Ina

N1 - Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

PY - 2023/3

Y1 - 2023/3

N2 - BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, representativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline ≥10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria.RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 ± 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.

AB - BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, representativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline ≥10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria.RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 ± 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.

KW - Humans

KW - Vital Capacity

KW - Disease Progression

KW - Lung Diseases, Interstitial/complications

KW - Scleroderma, Systemic/drug therapy

KW - Lung

U2 - 10.1016/j.chest.2022.09.044

DO - 10.1016/j.chest.2022.09.044

M3 - SCORING: Journal article

C2 - 36244404

VL - 163

SP - 586

EP - 598

JO - CHEST

JF - CHEST

SN - 0012-3692

IS - 3

ER -