Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

TY - JOUR

T1 - Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

AU - Kuster, Simon

AU - Jordan, Suzana

AU - Elhai, Muriel

AU - Held, Ulrike

AU - Steigmiller, Klaus

AU - Bruni, Cosimo

AU - Cacciapaglia, Fabio

AU - Vettori, Serena

AU - Siegert, Elise

AU - Rednic, Simona

AU - Codullo, Veronica

AU - Airo, Paolo

AU - Braun-Moscovici, Yolanda

AU - Hunzelmann, Nicolas

AU - Joao Salvador, Maria

AU - Riccieri, Valeria

AU - Gheorghiu, Ana-Maria

AU - Alegre Sancho, Juan José

AU - Romanowska-Prochnicka, Katarzyna

AU - Castellví, Ivan

AU - Kötter, Ina

AU - Truchetet, Marie-Elise

AU - López-Longo, F J

AU - Novikov, Pavel I

AU - Giollo, Alessandro

AU - Shirai, Yuichiro

AU - Belloli, Laura

AU - Zanatta, Elisabetta

AU - Hachulla, Eric

AU - Smith, Vanessa

AU - Denton, Chris

AU - Ionescu, Ruxandra M

AU - Schmeiser, Tim

AU - Distler, Joerg H W

AU - Gabrielli, Armando

AU - Hoffmann-Vold, Anna-Maria

AU - Kuwana, Masataka

AU - Allanore, Yannick

AU - Distler, Oliver

AU - EUSTAR Collaborators

N1 - © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2022/11

Y1 - 2022/11

N2 - OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

AB - OBJECTIVES: Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.METHODS: Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.RESULTS: Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.CONCLUSION: Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

KW - Humans

KW - United States

KW - Pulmonary Fibrosis/etiology

KW - Propensity Score

KW - Scleroderma, Systemic/complications

KW - Antibodies, Monoclonal, Humanized/adverse effects

U2 - 10.1136/rmdopen-2022-002477

DO - 10.1136/rmdopen-2022-002477

M3 - SCORING: Journal article

C2 - 36328401

VL - 8

JO - RMD OPEN

JF - RMD OPEN

SN - 2056-5933

IS - 2

M1 - e002477

ER -