Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study

Pilar Brito-Zerón; Alejandra Flores-Chávez; Ildiko Fanny Horváth; Astrid Rasmussen; Xiaomei Li; Peter Olsson; Arjan Vissink; Roberta Priori; Berkan Armagan; Gabriela Hernandez-Molina; Sonja Praprotnik; Luca Quartuccio; Nevsun Inanç; Burcugül Özkızıltaş; Elena Bartoloni; Agata Sebastian; Vasco C Romão; Roser Solans; Sandra G Pasoto; Maureen Rischmueller; Carlos Galisteo; Yasunori Suzuki; Virginia Fernandes Moça Trevisani; Cecilia Fugmann; Andrés González-García; Francesco Carubbi; Ciprian Jurcut; Toshimasa Shimizu; Soledad Retamozo; Fabiola Atzeni; Benedikt Hofauer; Sheila Melchor-Díaz; Tamer Gheita; Miguel López-Dupla; Eva Fonseca-Aizpuru; Roberto Giacomelli; Marcos Vázquez; Sandra Consani; Miriam Akasbi; Hideki Nakamura; Antónia Szántó; A Darise Farris; Li Wang; Thomas Mandl; Angelica Gattamelata; Levent Kilic; Katja Perdan Pirkmajer; Kerem Abacar; Abdurrahman Tufan; Salvatore de Vita; Hendrika Bootsma; Sjögren Big Data Consortium

doi:10.1016/j.eclinm.2023.102062

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study

Pilar Brito-Zerón, Alejandra Flores-Chávez, Ildiko Fanny Horváth, Astrid Rasmussen, Xiaomei Li, Peter Olsson, Arjan Vissink, Roberta Priori, Berkan Armagan, Gabriela Hernandez-Molina, Sonja Praprotnik, Luca Quartuccio, Nevsun Inanç, Burcugül Özkızıltaş, Elena Bartoloni, Agata Sebastian, Vasco C Romão, Roser Solans, Sandra G Pasoto, Maureen RischmuellerCarlos Galisteo, Yasunori Suzuki, Virginia Fernandes Moça Trevisani, Cecilia Fugmann, Andrés González-García, Francesco Carubbi, Ciprian Jurcut, Toshimasa Shimizu, Soledad Retamozo, Fabiola Atzeni, Benedikt Hofauer, Sheila Melchor-Díaz, Tamer Gheita, Miguel López-Dupla, Eva Fonseca-Aizpuru, Roberto Giacomelli, Marcos Vázquez, Sandra Consani, Miriam Akasbi, Hideki Nakamura, Antónia Szántó, A Darise Farris, Li Wang, Thomas Mandl, Angelica Gattamelata, Levent Kilic, Katja Perdan Pirkmajer, Kerem Abacar, Abdurrahman Tufan, Salvatore de Vita, Hendrika Bootsma, Sjögren Big Data Consortium

Reumatologi

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.

METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.

FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.

INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.

FUNDING: Novartis.

Originalspråk	engelska
Artikelnummer	102062
Sidor (från-till)	102062
Tidskrift	EClinicalMedicine
Volym	61
DOI	https://doi.org/10.1016/j.eclinm.2023.102062
Status	Published - 2023 juli

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Reumatologi och inflammation

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10.1016/j.eclinm.2023.102062Licens: CC BY

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Brito-Zerón, P., Flores-Chávez, A., Horváth, I. F., Rasmussen, A., Li, X., Olsson, P., Vissink, A., Priori, R., Armagan, B., Hernandez-Molina, G., Praprotnik, S., Quartuccio, L., Inanç, N., Özkızıltaş, B., Bartoloni, E., Sebastian, A., Romão, V. C., Solans, R., Pasoto, S. G., ... Sjögren Big Data Consortium (2023). Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study. EClinicalMedicine, 61, 102062. Article 102062. https://doi.org/10.1016/j.eclinm.2023.102062

@article{74639d986f7243bd91de4c25e8119d8d,

title = "Mortality risk factors in primary Sj{\"o}gren syndrome: a real-world, retrospective, cohort study",

abstract = "BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sj{\"o}gren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sj{\"o}gren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sj{\"o}gren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sj{\"o}gren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sj{\"o}gren-cause death identified five Sj{\"o}gren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.FUNDING: Novartis.",

author = "Pilar Brito-Zer{\'o}n and Alejandra Flores-Ch{\'a}vez and Horv{\'a}th, {Ildiko Fanny} and Astrid Rasmussen and Xiaomei Li and Peter Olsson and Arjan Vissink and Roberta Priori and Berkan Armagan and Gabriela Hernandez-Molina and Sonja Praprotnik and Luca Quartuccio and Nevsun Inan{\c c} and Burcug{\"u}l {\"O}zkızılta{\c s} and Elena Bartoloni and Agata Sebastian and Rom{\~a}o, {Vasco C} and Roser Solans and Pasoto, {Sandra G} and Maureen Rischmueller and Carlos Galisteo and Yasunori Suzuki and Trevisani, {Virginia Fernandes Mo{\c c}a} and Cecilia Fugmann and Andr{\'e}s Gonz{\'a}lez-Garc{\'i}a and Francesco Carubbi and Ciprian Jurcut and Toshimasa Shimizu and Soledad Retamozo and Fabiola Atzeni and Benedikt Hofauer and Sheila Melchor-D{\'i}az and Tamer Gheita and Miguel L{\'o}pez-Dupla and Eva Fonseca-Aizpuru and Roberto Giacomelli and Marcos V{\'a}zquez and Sandra Consani and Miriam Akasbi and Hideki Nakamura and Ant{\'o}nia Sz{\'a}nt{\'o} and Farris, {A Darise} and Li Wang and Thomas Mandl and Angelica Gattamelata and Levent Kilic and Pirkmajer, {Katja Perdan} and Kerem Abacar and Abdurrahman Tufan and {de Vita}, Salvatore and Hendrika Bootsma and {Sj{\"o}gren Big Data Consortium}",

note = "{\textcopyright} 2023 The Author(s).",

year = "2023",

month = jul,

doi = "10.1016/j.eclinm.2023.102062",

language = "English",

volume = "61",

pages = "102062",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Lancet Publishing Group",

}

Brito-Zerón, P, Flores-Chávez, A, Horváth, IF, Rasmussen, A, Li, X, Olsson, P, Vissink, A, Priori, R, Armagan, B, Hernandez-Molina, G, Praprotnik, S, Quartuccio, L, Inanç, N, Özkızıltaş, B, Bartoloni, E, Sebastian, A, Romão, VC, Solans, R, Pasoto, SG, Rischmueller, M, Galisteo, C, Suzuki, Y, Trevisani, VFM, Fugmann, C, González-García, A, Carubbi, F, Jurcut, C, Shimizu, T, Retamozo, S, Atzeni, F, Hofauer, B, Melchor-Díaz, S, Gheita, T, López-Dupla, M, Fonseca-Aizpuru, E, Giacomelli, R, Vázquez, M, Consani, S, Akasbi, M, Nakamura, H, Szántó, A, Farris, AD, Wang, L, Mandl, T, Gattamelata, A, Kilic, L, Pirkmajer, KP, Abacar, K, Tufan, A, de Vita, S, Bootsma, H & Sjögren Big Data Consortium 2023, 'Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study', EClinicalMedicine, vol. 61, 102062, s. 102062. https://doi.org/10.1016/j.eclinm.2023.102062

TY - JOUR

T1 - Mortality risk factors in primary Sjögren syndrome

T2 - a real-world, retrospective, cohort study

AU - Brito-Zerón, Pilar

AU - Flores-Chávez, Alejandra

AU - Horváth, Ildiko Fanny

AU - Rasmussen, Astrid

AU - Li, Xiaomei

AU - Olsson, Peter

AU - Vissink, Arjan

AU - Priori, Roberta

AU - Armagan, Berkan

AU - Hernandez-Molina, Gabriela

AU - Praprotnik, Sonja

AU - Quartuccio, Luca

AU - Inanç, Nevsun

AU - Özkızıltaş, Burcugül

AU - Bartoloni, Elena

AU - Sebastian, Agata

AU - Romão, Vasco C

AU - Solans, Roser

AU - Pasoto, Sandra G

AU - Rischmueller, Maureen

AU - Galisteo, Carlos

AU - Suzuki, Yasunori

AU - Trevisani, Virginia Fernandes Moça

AU - Fugmann, Cecilia

AU - González-García, Andrés

AU - Carubbi, Francesco

AU - Jurcut, Ciprian

AU - Shimizu, Toshimasa

AU - Retamozo, Soledad

AU - Atzeni, Fabiola

AU - Hofauer, Benedikt

AU - Melchor-Díaz, Sheila

AU - Gheita, Tamer

AU - López-Dupla, Miguel

AU - Fonseca-Aizpuru, Eva

AU - Giacomelli, Roberto

AU - Vázquez, Marcos

AU - Consani, Sandra

AU - Akasbi, Miriam

AU - Nakamura, Hideki

AU - Szántó, Antónia

AU - Farris, A Darise

AU - Wang, Li

AU - Mandl, Thomas

AU - Gattamelata, Angelica

AU - Kilic, Levent

AU - Pirkmajer, Katja Perdan

AU - Abacar, Kerem

AU - Tufan, Abdurrahman

AU - de Vita, Salvatore

AU - Bootsma, Hendrika

AU - Sjögren Big Data Consortium

PY - 2023/7

Y1 - 2023/7

N2 - BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.FUNDING: Novartis.

AB - BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.METHODS: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FINDINGS: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death.INTERPRETATION: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.FUNDING: Novartis.

U2 - 10.1016/j.eclinm.2023.102062

DO - 10.1016/j.eclinm.2023.102062

M3 - Article

C2 - 37457113

SN - 2589-5370

VL - 61

SP - 102062

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 102062

ER -