Development of a multivariable prediction model for progression of systemic sclerosis-associated interstitial lung disease.

To develop a multivariable model for predicting the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) over 52 weeks. We used logistic regression models to analyse associations between candidate predictors assessed at baseline and progression of SSc-ILD (absolute decline in forced vital capacity (FVC) % predicted >5% or death) over 52 weeks in the placebo group of the SENSCIS trial. Analyses were performed in the overall placebo group and in a subgroup with early and/or inflammatory SSc and/or severe skin fibrosis (<18 months since first non-Raynaud symptom, elevated inflammatory markers, and/or modified Rodnan skin score (mRSS) >18) at baseline. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). In the overall placebo group (n=288), the performance of the final multivariable model for predicting SSc-ILD progression was moderate (apparent AUC: 0.63). A stronger model, with an apparent AUC of 0.75, was developed in the subgroup with early and/or inflammatory SSc and/or severe skin fibrosis at baseline (n=155). This model included diffusing capacity of the lung for carbon monoxide (DLco) % predicted, time since first non-Raynaud symptom, mRSS, anti-topoisomerase I antibody status and mycophenolate use. Prediction of the progression of SSc-ILD may require different approaches in distinct subgroups of patients. Among patients with SSc-ILD and early and/or inflammatory SSc and/or severe skin fibrosis, a nomogram based on a multivariable model may be of value for identifying patients at risk of short-term progression.

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Competing interests: MK reports grants from Boehringer Ingelheim, Ono, MBL; consulting fees from Argenx, AstraZeneca, Boehringer Ingelheim, Chugai, GlaxoSmithKline, Kissei, Mochida; speaker fees from AbbVie, Asahi Kasei, Boehringer Ingelheim, Chugai, Eisai, Janssen, Ono; royalties/licenses from MBL. JA reports no disclosures. A-MH-V reports grants from Boehringer Ingelheim and Janssen; consulting fees from Arxx Therapeutics, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Janssen, Medscape; speaker fees from Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Roche; and support for attending meetings from Boehringer Ingelheim, Medscape, Roche; she is a EULAR study group leader on the lung in rheumatic and musculoskeletal diseases and a convener of the ERS/EULAR CTD-ILD guidelines. VS reports a grant from the Belgian Fund for Scientific Research in Rheumatic Diseases; research support from Boehringer Ingelheim; she is a senior clinical investigator of the Research Foundation—Flanders (Belgium) (FWO) (1.8.029.20N) (which had no involvement with the study reported in this manuscript). VS also reports consulting fees from Argenx BV, Boehringer Ingelheim, Janssen-Cilag, WebMD Global LLC; speaker fees from Boehringer Ingelheim, Galapagos, Janssen-Cilag; payment from BKC Moving Media Makers B.V.; support for attending congresses from Boehringer Ingelheim; participation on an advisory board and being an educational chair for Janssen-Cilag. VS has unpaid roles as chair of the EULAR study group on microcirculation in rheumatic diseases; as co-chair of the ACR study group on microcirculation and SCTC working group on capillaroscopy; and as a member of the Steering Committee of ERN-ReCONNET. GT and MA are employees of Boehringer Ingelheim. OD reports grants from Boehringer Ingelheim, Kymera, Mitsubishi Tanabe; consulting fees from 4P-Pharma, AbbVie, Acceleron, Alcimed, Altavant Sciences, Amgen, AnaMar, Arxx Therapeutics, AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Galapagos, Glenmark, Gossamer, Horizon Therapeutics, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus Biosciences, Redx Pharma, Roivant, Topadur, UCB; speaker fees from Bayer, Boehringer Ingelheim, Janssen, Medscape; and a patent issued for mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143). OD also reports being Chair of the Executive Committee of the FOREUM Foundation, Co-Chair and President of the ERS/EULAR guidelines and EUSTAR, a member of the Board of Trustees of the Swiss Clinical Quality Management in Rheumatic Diseases, and the Hartmann Müller Foundation, a Senat member of the Swiss Academy of Medical Sciences, and Co-Founder of Citus AG.