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

Kuster S, Jordan S, Elhai M, Held U, Steigmiller K, Bruni C, Cacciapaglia F, Vettori S, Siegert E, Rednic S, Codullo V, Airo P, Braun-Moscovici Y, Hunzelmann N, Joao Salvador M, Riccieri V, Gheorghiu AM, Alegre Sancho JJ, Romanowska-Prochnicka K, Castellví I, Kötter I, Truchetet ME, López-Longo FJ, Novikov PI, Giollo A, Shirai Y, Belloli L, Zanatta E, Hachulla E, Smith V, Denton C, Ionescu RM, Schmeiser T, Distler J, Gabrielli A, Hoffmann-Vold AM, Kuwana M, Allanore Y, Distler O (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 8

Article Number: e002477

Journal Issue: 2

DOI: 10.1136/rmdopen-2022-002477

Abstract

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.

Authors with CRIS profile

Involved external institutions

Universitätsspital Zürich (USZ) Switzerland (CH) University of Zurich / Universität Zürich (UZH) Switzerland (CH) Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari Italy (IT) Università degli studi della Campania Luigi Vanvitelli Italy (IT) Iuliu Hațieganu University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie "Iuliu Hațieganu" (UMF Cluj) Romania (RO) Policlinico San Matteo Pavia Fondazione IRCCS Italy (IT) Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Italy (IT) Technion - Israel Institute of Technology Israel (IL) Universität zu Köln Germany (DE) Centro Hospitalar e Universitário de Coimbra (CHUC) Portugal (PT) Università degli studi "La Sapienza" Italy (IT) Carol Davila University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie „Carol Davila” (UMF București) Romania (RO) Hospital Universitario Dr. Peset Aleixandre Spain (ES) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu Poland (PL) Hospital de la Santa Creu i Sant Pau Spain (ES) Hospital General Universitario Gregorio Marañón Spain (ES) Centre Hospitalier Universitaire de Bordeaux / CHU Bordeaux France (FR) University of Verona / Università degli Studi di Verona Italy (IT) Nippon Medical School Japan (JP) Ospedale Niguarda Ca' Granda / ASST Grande Ospedale Metropolitano Niguarda Italy (IT) University of Padua / Universita degli Studi di Padova Italy (IT) LILLE 1 University - Science and Technology France (FR) University Hospital Ghent Belgium (BE) UCL Medical School United Kingdom (GB) Università Politecnica delle Marche (UNIVPM) / Marche Polytechnic University Italy (IT) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Hôpital Cochin France (FR)

How to cite

APA:

Kuster, S., Jordan, S., Elhai, M., Held, U., Steigmiller, K., Bruni, C.,... Distler, O. (2022). Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort. RMD Open, 8(2). https://dx.doi.org/10.1136/rmdopen-2022-002477

MLA:

Kuster, Simon, et al. "Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort." RMD Open 8.2 (2022).

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