Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort
- PMID: 38265945
- DOI: 10.1016/S2665-9913(22)00217-X
Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort
Abstract
Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis.
Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed.
Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81-0·84 for cutaneous only vs 0·84, 0·82-0·85 for antibody only vs 0·84, 0·83-0·86 for combined) or for progression-free survival (0·70, 0·69-0·71 vs 0·71, 0·70-0·72 vs 0·71, 0·70-0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46-0·71 for antibody only vs 0·29, 0·19-0·39 for cutaneous only) and disease progression (0·36, 0·29-0·46 vs 0·21, 0·14-0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70-0·74 for antibody only vs 0·66, 0·64-0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75-0·77 vs 0·71, 0·70-0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement.
Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management.
Funding: World Scleroderma Foundation.
Copyright © 2022 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Interests ME received speaking fees from Bristol Myers Squibb (BMS) and travel support for congress from Janssen. AB-G received payment or honoraria for lectures, presentations, speakers bureau, manuscript writing or educational events from Boehringer Ingelheim, Abbvie, Pfizer, Eli Lily, Novartis, Sandos, Janssen, and Roche; and support for attending meetings or travel from Abbvie, Boehringer Ingelheim, and Pfizer. JdV-B received grants from Janssen-Cilag (Johnson & Johnson), ZonMW (Dutch governmental funding party), Dutch Patient Organisation for Systemic Autoimmune Diseases (patient organisation), ReumaNederland grant (patient organisation) all paid to their institution; consulting fees from Boehringer Ingelheim and Abbvie all paid to their institution, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Janssen-Cilag. JdV-B's travel costs for EUSTAR World Scleroderma Foundation course (March 2022) were funded by EUSTAR/WSF. JdV-B is a board member of Autoimmune Research and Collaboration Hub (Netherlands); which is unpaid. JHWD received grants from the German Research Foundation (grant numbers: DI 1537/14–1, DI 1537/17–1, DI 1537/20–1, DI 1537/22–1, DI 1537/23–1, SFB CRC1181 [project C01], and SFB TR221/ project number 324392634 [B04]), the Interdisciplinary Center for Clinical Research Erlangen (grant A79), the Wilhelm-Sander-Foundation (grant 2013.056.1), the Else-Kröner-Fresenius-Foundation (grant numbers 2014_A47 and 2014_A184), Bundesministerium für Bildung und Forschung, MASCARA programme, project 2 (grant number 01EC1903A), a Career Support Award of Medicine from the Ernst Jung Foundation; consulting fees from AbbVie, Active Biotech, Anamar, ARXX Therapeutics, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, Janssen, Novartis; payment or honoria from Biotech, AbbVie, Active Biotech, Anamar, ARXX Therapeutics, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, Janssen, Novartis; support for attending meetings and travel from Boehringer Ingelheim; has stock or stock options in 4D science; received equipment, materials, drugs, medical writing, gifts, or other services from Anamar, ARXX Therapeutics, BMS, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, CSL Behring, Galapagos, GlaxoSmithKline, Inventiva, Kiniksa, Sanofi-Aventis, RedX, and UCB; and is the scientific lead of FibroCure. FDG received grants from National Institute for Health and Care Research, Medical Research Council, Scleroderma and Raynauds UK, Abbvie, Astrazeneca, Boegringer Ingelheim, Capella, Chemomab, and Mitsubishi-Tanabe; consulting fees from Astrazeneca, Boehringer Ingelheim, Capella, Chemomab, and Mitsubishi-Tanabe; and honoria for lectures, presentations, speakers bureau, manuscript writing or educational events and support for attending meetings or travel from Janssen. FDG is president of EUSTAR. FAM received consulting fees from Aurinia Pharmaceuticals. DEF received grants or research support from Galapagos, Amgen, Corbus, GlaxoSmithKline, NIH, Mitsubishi, Novartis, Pfizer, Sanofi, Roche, Genentech, Emerald, Prometheus, and Horizon; and consulting fees from Abbive. Actelion, BMS, Corbus, Galapagos, GlaxoSmithKline, National Institutes of Health, Novartis, Pfizer, Sanofi Roche, and Genentech; and consulting fees and speakers bureau continuing medical education honoria from Prometheus and Horizon. CdlP received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Nordic Pharma, Pfizer, and Janssen, and support for attending meetings and travel from Galapagos and Boehringer Ingelheim. A-MH-V received grants or contracts from Actelion; ARXX therapeutics; Boehringer Ingelheim; Roche; Bayer; Merck, Sharp, and Dohme; Lilly; and Medscape, consulting fees from Actelion; ARXX therapeutics; Boehringer Ingelheim; Roche; Merck, Sharp, and Dohme; Lilly; and Medscape, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or education events from Actelion; ARXX therapeutics; Boehringer Ingelheim; Roche; Bayer; Merck, Sharp, and Dohme; Lilly; and Medscape, and support for attending meetings and travel from Actelion, Boehringer Ingelheim, and Medscape. A-MH-V also has a leadership or fiduciary role in the European Alliance of Associations for Rheumatology (EULAR) quality of care committee, Pulmonary Hypertension Nordic group, and is the EULAR convenor of European Respiratory Society and EULAR Connective Tissue Disease-Related Intersititial Lung Disease. AG received grants or contracts from Janssen, Boehringer Ingelheim, and Roche: sponsors of EUSTAR/World Scleroderma Foundation systemic sclerosis virtual school 2022. OD received research grants from Kymera, Mitsubishi Tanabe, and Boehringer Ingelheim, consulting fees for systemic sclerosis and its complications or for arthritis from 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant Sciences, Amgen, AnaMar, ARXX, AstraZeneca, Blade Therapeutics, Bayer, Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, 4P Science, Galapagos, Glenmark, Gossamer, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, Merck Sharp and Dohme, Novartis, Prometheus Biosciences, Redxpharma, Roivant, Sanofi, Topadur and Pfizer, and speaker fees for systemic sclerosis and its complications from Bayer, Boehringer Ingelheim, Janssen and Medscape. OD has issued a patent for “mir-29 for the treatment of systemic sclerosis” (patent number US8247389, EP2331143), and is the chair of the executive committee for the Foundation for Research in Rheumatology, the co-chair for the European Respiratory Society and EULAR Guidelines, a member of the Swiss Clinical Quality Management in Rheumatic Diseases’ board of trustees, a senat member for the Swiss Academy of Medical Sciences, and a member of the board for trustees for Hartmann Müller Foundation. YA received consultancy fees from Boehringer Ingelheim, Topadur, Abbvie, Mylan, Prometheus, Janssen, and Medsenic, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, and participated on a data safety monitory board or advisory board for Boehringer Ingelheim, Astra Zeneca, and Prometheus. All other authors declare no competing interests.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
