Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis
Tóm tắt
Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.
Tài liệu tham khảo
Hachulla E, Launay D. Diagnosis and classification of systemic sclerosis. Clin Rev Allergy Immunol. 2011;40(2):78–83. https://doi.org/10.1007/s12016-010-8198-y.
LeRoy EC, Medsger TA. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28(7):1573–6.
Furst DE, Clements PJ, Steen VD, Medsger TA, Masi AT, D'Angelo WA, et al. The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol. 1998;25(1):84–8.
Kumánovics G, Péntek M, Bae S, Opris D, Khanna D, Furst DE, et al. Assessment of skin involvement in systemic sclerosis. Rheumatology (Oxford). 2017;56(suppl_5):v53–66. https://doi.org/10.1093/rheumatology/kex202.
Khanna D, Furst DE, Clements PJ, Allanore Y, Baron M, Czirjak L, et al. Standardization of the modified Rodnan skin score for use in clinical trials of systemic sclerosis. J Scleroderma Relat Disord. 2017;2(1):11–8. https://doi.org/10.5301/jsrd.5000231.
Shand L, Lunt M, Nihtyanova S, Hoseini M, Silman A, Black CM, et al. Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model. Arthritis Rheum. 2007;56(7):2422–31.
Perera A, Fertig N, Lucas M, Rodriguez-Reyna TS, Hu P, Steen VD, et al. Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti–topoisomerase I antibody. Arthritis Rheum. 2007;56(8):2740–6.
Avouac J, Walker UA, Hachulla E, Riemekasten G, Cuomo G, Carreira PE, et al. Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis. 2016;75:103–9. https://doi.org/10.1136/annrheumdis-2014-205295.
Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton CP, et al. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis. 2015;74(6):1124–31. https://doi.org/10.1136/annrheumdis-2014-205226.
Herrick AL, Peytrignet S, Lunt M, Pan X, Hesselstrand R, Mouthon L, et al. Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study. Ann Rheum Dis. 2018;77(4):563–70. https://doi.org/10.1136/annrheumdis-2017-211912.
Distler O, Allanore Y, Denton C, Kuwana M, Matucci-Cerinic M, Pope J, et al. Riociguat in Patients with Early Diffuse Cutaneous Systemic Sclerosis: a Randomized, Double-Blind, Placebo-Controlled Phase IIb Study (RISE-SSc). Arthritis Rheumatol. 2018;70(suppl 10) https://acrabstracts.org/abstract/riociguat-in-patients-with-early-diffuse-cutaneous-systemic-sclerosis-a-randomized-double-blind-placebo-controlled-phase-iib-study-rise-ssc/. Accessed 9 Nov 2018.
Khanna D, Lin C, Kuwana M, Allanore Y, Batalov A, Butrimiene I, et al. Efficacy and safety of tocilizumab for the treatment of systemic sclerosis: results from a phase 3 randomized controlled trial [abstract]. Arthritis Rheumatol. 2018;70(suppl 10) https://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-for-the-treatment-of-systemic-sclerosis-results-from-a-phase-3-randomized-controlled-trial/. Accessed 9 Nov 2018.
Khanna D, Spino C, Johnson S, Chung L, Whitfield ML, et al. Abatacept in early diffuse cutaneous systemic sclerosis: results of a phase II investigator-initiated, multicenter, double-blind, randomized, placebo-controlled trial. Arthritis Rheumatol. 2020;72(1):125–36. https://doi.org/10.1002/art.41055 Epub 2019 Dec 10.
Masi AT. Subcommittee For Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980;23:581–90. https://doi.org/10.1002/art.1780230510.
Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheum. 2013;65(11):2737–47. https://doi.org/10.1002/art.38098.
Domsic RT, Rodriguez-Reyna T, Lucas M, Fertig N, Medsger TA. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis. 2010;70:104–9. https://doi.org/10.1136/ard.2009.127621.
McCulloch CE, Lin H, Slate EH, Turnbull BW. Discovering subpopulation structure with latent class mixed models. Stat Med. 2002;21(3):417–29.
Verbeke G, Molenberghs G. Linear mixed models for longitudinal data. New-York: Springer-Verlag; 2000. https://doi.org/10.1007/978-1-4419-0300-6.
Schreiber JB. Latent class analysis: an example for reporting results. Res Social Adm Pharm. 2017;13(6):1196–201. https://doi.org/10.1016/j.sapharm.2016.11.011.
Van de Schoot R, Sijbrandij M, Winter SD, Depaoli S, Vermunt JK, van de Schoot R, et al. The GRoLTS-Checklist: guidelines for reporting on latent trajectory studies. Struct Equ Model Multidiscip J. 2017;24:451–67. https://doi.org/10.1080/10705511.2016.1247646.
Clements P, Lachenbruch P, Furst D, Paulus H. The course of skin involvement in systemic sclerosis over three years in a trial of chlorambucil versus placebo. Arthritis Rheum. 1993;36(11):1575–9.
Medsger TA Jr. Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum Dis Clin North Am. 2003;29(2):255–73. Elsevier. https://doi.org/10.1016/S0889-857X(03)00023-1.
Nihtyanova SI, Sari A, Harvey JC, Leslie A, Derrett-Smith EC, et al. Using autoantibodies and cutaneous subset to develop outcome-based disease classification in systemic sclerosis. Arthritis Rheumatol. 2019. https://doi.org/10.1002/art.41153 [Epub ahead of print].
Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR scleroderma trials and research group database. Ann Rheum Dis. 2007;66(6):754–63. https://doi.org/10.1136/ard.2006.062901.
Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR scleroderma trials and research (EUSTAR) database. Ann Rheum Dis. 2010;69(10):1809–15. https://doi.org/10.1136/ard.2009.114264.
Frantz C, Huscher D, Avouac J, Hachulla E, Balbir-Gurman A, et al. Outcomes of limited cutaneous systemic sclerosis patients: results on more than 12,000 patients from the EUSTAR database. Autoimmun Rev. 2020;19(2):102452. https://doi.org/10.1016/j.autrev.2019.102452.
Meier FMP, Frommer KW, Dinser R, Walker UA, Czirjak L, et al. Update on the profile of the EUSTAR cohort: an analysis of the EULAR scleroderma trials and research group database. Ann Rheum Dis. 2012;71(8):1355–60. https://doi.org/10.1136/annrheumdis-2011-200742.
Sobanski V, Giovannelli J, Allanore Y, Riemekasten G, Cozzi F, Distler O, et al. Phenotypes determined by cluster analysis and their survival in the prospective EUSTAR cohort of patients with systemic sclerosis. Arthritis Rheumatol. 2019;71(9):1553–70. https://doi.org/10.1002/art.40906.
Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, et al. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS). Ann Rheum Dis. 2017;76(7):1207–18. https://doi.org/10.1136/annrheumdis-2016-210503.
Merkel PA, Silliman NP, Clements PJ, Denton CP, Furst DE, Mayes MD, et al. Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2012;64(10):3420–9. https://doi.org/10.1002/art.34427.
Amjadi S, Maranian P, Furst DE, Clements PJ, Wong WK, Postlethwaite AE, et al. Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum. 2009;60(8):2490–8. https://doi.org/10.1002/art.24681.
Johnson SR, Soowamber ML, Fransen J, Khanna D, Van Den Hoogen F, Baron M, et al. There is a need for new systemic sclerosis subset criteria. A content analytic approach. Scand J Rheumatol. 2018;47:62–70. https://doi.org/10.1080/03009742.2017.1299793.
Srivastava N, Hudson M, Tatibouet S, Wang M, Baron M, et al. Thinking outside the box--the associations with cutaneous involvement and autoantibody status in systemic sclerosis are not always what we expect. Semin Arthritis Rheum. 2015;45(2):184–9. https://doi.org/10.1016/j.semarthrit.2015.04.009.
Kranenburg P, van den Hombergh WMT, Knaapen-Hans HKA, van den Hoogen FHJ, Fransen J, et al. Survival and organ involvement in patients with limited cutaneous systemic sclerosis and anti-topoisomerase-I antibodies: determined by skin subtype or auto-antibody subtype? A long-term follow-up study. Rheumatology (Oxford). 2016;55(11):2001–8. https://doi.org/10.1093/rheumatology/kew298.
Wu W, Jordan S, Graf N, de Oliveira PJ, Curram J, Allanore Y, et al. Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort. Ann Rheum Dis. 2019;78(5):648–56. https://doi.org/10.1136/annrheumdis-2018-213455.
Zheng B, Nevskaya T, Baxter CA, Ramey DR, Pope JE, et al. Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity. Rheumatology (Oxford). 2019. https://doi.org/10.1093/rheumatology/kez299 [Epub ahead of print].
Khanna D, Clements PJ, Volkmann ER, Wilhalme H, Tseng C-H, Furst DE, et al. Minimal clinically important differences for the modified Rodnan skin score: results from the scleroderma lung studies (SLS-I and SLS-II). Arthritis Res Ther. 2019;21(1):23. https://doi.org/10.1186/s13075-019-1809-y.
Czirják L, Nagy Z, Aringer M, Riemekasten G, Matucci-Cerinic M, Furst DE, et al. The EUSTAR model for teaching and implementing the modified Rodnan skin score in systemic sclerosis. Ann Rheum Dis. 2007;66(7):966–9. https://doi.org/10.1136/ard.2006.066530.
Park JW, Ahn GY, Kim J-W, Park ES, Kang J-H, Chang SH, et al. Impact of EUSTAR standardized training on accuracy of modified Rodnan skin score in patients with systemic sclerosis. Int J Rheum Dis. 2019;22(1):96–102. https://doi.org/10.1111/1756-185X.13433.