Evidence map›Paper›PMID 35012623›Full record

ArticleArthritis research & therapy2022

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

Michael Kreuter, Francesco Del Galdo, Corinna Miede, Dinesh Khanna, Wim A Wuyts, Laura K Hummers, Margarida Alves, Nils Schoof, Christian Stock, Yannick Allanore

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02597933 (A Double Blind, Randomised, Placebo-controlled Trial Evaluating Efficacy and Safety of Oral Nintedanib Treatment for at Least 52 Weeks in Patients With Systemic Sclerosis Associated Interstitial Lung Disease), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02597933 phase3completednot on this map

A Double Blind, Randomised, Placebo-controlled Trial Evaluating Efficacy and Safety of Oral Nintedanib Treatment for at Least 52 Weeks in Patients With Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)

TypeinterventionalSponsorBoehringer IngelheimRan2015 to 2018Enrolled580ConditionsScleroderma, SystemicArmsNintedanib, Placebo
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 8 institutions in 5 countries.

Michael Kreuter *Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Röntgenstrasse 1, 69121, Heidelberg, Germany. kreuter@uni-heidelberg.de.ORCID 0000-0003-4402-2159
Francesco Del Galdo *Scleroderma Programme NIHR BRC and Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Corinna Miedemainanalytics GmbH, Sulzbach/Taunus, Germany.
Dinesh KhannaDivision of Rheumatology/Department of Internal Medicine, Scleroderma Program, University of Michigan, Ann Arbor, MI, USA.
Wim A WuytsInterstitial Lung Diseases Unit, University Hospitals Leuven, Leuven, Belgium.
Laura K HummersDivision of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Margarida AlvesBoehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
Nils SchoofBoehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
Christian StockBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
Yannick AllanoreDepartment of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France.
Boehringer Ingelheim (Germany) · DEDélégation Paris 5 · FRHeidelberg University · DEJohns Hopkins University · USKU Leuven · BEReference Institute for Bioanalytics · DEUniversity of Leeds · GBUniversity of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInterstitial 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.

methodsWe 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.

resultsThere 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®.

conclusionsThe 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 registrationClinicalTrials.gov NCT02597933 . Registered on 8 October 2015.

Indexed as

Lung Diseases, InterstitialScleroderma, SystemicDisease ProgressionHospitalizationHumansLungForced vital capacityHospitalisationJoint modelSENSCISSurrogate endpointSystemic sclerosis-associated interstitial lung disease

Identifiers

PMID35012623
PMCPMC8751320
OpenAlexW4221040094

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.