Effectiveness and safety of tocilizumab in patients with systemic sclerosis : a propensity score matched controlled observational study of the EUSTAR cohort
© 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..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
RMD open - 8(2022), 2 vom: 01. Nov. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kuster, Simon [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal, Humanized |
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| Anmerkungen: |
Date Completed 07.11.2022 Date Revised 14.11.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1136/rmdopen-2022-002477 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM348423284 |
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| 100 | 1 | |a Kuster, Simon |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effectiveness and safety of tocilizumab in patients with systemic sclerosis |b a propensity score matched controlled observational study of the EUSTAR cohort |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 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. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a autoimmune diseases | |
| 650 | 4 | |a biological therapy | |
| 650 | 4 | |a systemic sclerosis | |
| 650 | 7 | |a tocilizumab |2 NLM | |
| 650 | 7 | |a I031V2H011 |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Jordan, Suzana |e verfasserin |4 aut | |
| 700 | 1 | |a Elhai, Muriel |e verfasserin |4 aut | |
| 700 | 1 | |a Held, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Steigmiller, Klaus |e verfasserin |4 aut | |
| 700 | 1 | |a Bruni, Cosimo |e verfasserin |4 aut | |
| 700 | 1 | |a Cacciapaglia, Fabio |e verfasserin |4 aut | |
| 700 | 1 | |a Vettori, Serena |e verfasserin |4 aut | |
| 700 | 1 | |a Siegert, Elise |e verfasserin |4 aut | |
| 700 | 1 | |a Rednic, Simona |e verfasserin |4 aut | |
| 700 | 1 | |a Codullo, Veronica |e verfasserin |4 aut | |
| 700 | 1 | |a Airo, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a Braun-Moscovici, Yolanda |e verfasserin |4 aut | |
| 700 | 1 | |a Hunzelmann, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Joao Salvador, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Riccieri, Valeria |e verfasserin |4 aut | |
| 700 | 1 | |a Gheorghiu, Ana-Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Alegre Sancho, Juan José |e verfasserin |4 aut | |
| 700 | 1 | |a Romanowska-Prochnicka, Katarzyna |e verfasserin |4 aut | |
| 700 | 1 | |a Castellví, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Kötter, Ina |e verfasserin |4 aut | |
| 700 | 1 | |a Truchetet, Marie-Elise |e verfasserin |4 aut | |
| 700 | 1 | |a López-Longo, F J |e verfasserin |4 aut | |
| 700 | 1 | |a Novikov, Pavel I |e verfasserin |4 aut | |
| 700 | 1 | |a Giollo, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Shirai, Yuichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Belloli, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Zanatta, Elisabetta |e verfasserin |4 aut | |
| 700 | 1 | |a Hachulla, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Vanessa |e verfasserin |4 aut | |
| 700 | 1 | |a Denton, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Ionescu, Ruxandra M |e verfasserin |4 aut | |
| 700 | 1 | |a Schmeiser, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Distler, Joerg H W |e verfasserin |4 aut | |
| 700 | 1 | |a Gabrielli, Armando |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffmann-Vold, Anna-Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Kuwana, Masataka |e verfasserin |4 aut | |
| 700 | 1 | |a Allanore, Yannick |e verfasserin |4 aut | |
| 700 | 1 | |a Distler, Oliver |e verfasserin |4 aut | |
| 700 | 0 | |a EUSTAR collaborators |e verfasserin |4 aut | |
| 700 | 1 | |a Becvar, Radim |e investigator |4 oth | |
| 700 | 1 | |a Cutolo, Maurizio |e investigator |4 oth | |
| 700 | 1 | |a Carreira, Patricia E |e investigator |4 oth | |
| 700 | 1 | |a Czirják, László |e investigator |4 oth | |
| 700 | 1 | |a Iudici, Michele |e investigator |4 oth | |
| 700 | 1 | |a Kucharz, Eugene J |e investigator |4 oth | |
| 700 | 1 | |a Coleiro, Bernard |e investigator |4 oth | |
| 700 | 1 | |a Bancel, Dominique Farge |e investigator |4 oth | |
| 700 | 1 | |a Hesselstrand, Roger |e investigator |4 oth | |
| 700 | 1 | |a Radic, Mislav |e investigator |4 oth | |
| 700 | 1 | |a Pellerito, Raffaele |e investigator |4 oth | |
| 700 | 1 | |a Damjanov, Nemanja |e investigator |4 oth | |
| 700 | 1 | |a Henes, Jörg |e investigator |4 oth | |
| 700 | 1 | |a Vera Ortiz-Santamaria, Stefan Heitmann |e investigator |4 oth | |
| 700 | 1 | |a Hasler, Paul |e investigator |4 oth | |
| 700 | 1 | |a Stamenkovic, Bojana |e investigator |4 oth | |
| 700 | 1 | |a Selmi, Carlo Francesco |e investigator |4 oth | |
| 700 | 1 | |a Tikly, Mohammed |e investigator |4 oth | |
| 700 | 1 | |a Ananieva, Lidia P |e investigator |4 oth | |
| 700 | 1 | |a Müller-Ladner, Ulf |e investigator |4 oth | |
| 700 | 1 | |a Engelhart, Merete |e investigator |4 oth | |
| 700 | 1 | |a Puente, Carlos de la |e investigator |4 oth | |
| 700 | 1 | |a Sunderkötter, Cord |e investigator |4 oth | |
| 700 | 1 | |a Ingegnoli, Francesca |e investigator |4 oth | |
| 700 | 1 | |a Mouthon, Luc |e investigator |4 oth | |
| 700 | 1 | |a Cantatore, Francesco Paolo |e investigator |4 oth | |
| 700 | 1 | |a Ullman, Susanne |e investigator |4 oth | |
| 700 | 1 | |a Pozzi, Maria Rosa |e investigator |4 oth | |
| 700 | 1 | |a Wiland, Piotr |e investigator |4 oth | |
| 700 | 1 | |a Vanthuyne, Marie |e investigator |4 oth | |
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| 700 | 1 | |a Krummel-Lorenz, Brigitte |e investigator |4 oth | |
| 700 | 1 | |a Herrmann, Kristine |e investigator |4 oth | |
| 700 | 1 | |a Langhe, Ellen De |e investigator |4 oth | |
| 700 | 1 | |a Anic, Branimir |e investigator |4 oth | |
| 700 | 1 | |a Yavuz, Sule |e investigator |4 oth | |
| 700 | 1 | |a Müller, Carolina de Souza |e investigator |4 oth | |
| 700 | 1 | |a Agachi, Svetlana |e investigator |4 oth | |
| 700 | 1 | |a Zenone, Thierry |e investigator |4 oth | |
| 700 | 1 | |a Stebbings, Simon |e investigator |4 oth | |
| 700 | 1 | |a Vacca, Alessandra |e investigator |4 oth | |
| 700 | 1 | |a Stamp, Lisa |e investigator |4 oth | |
| 700 | 1 | |a Solanki, Kamal |e investigator |4 oth | |
| 700 | 1 | |a Veale, Douglas |e investigator |4 oth | |
| 700 | 1 | |a Loyo, Esthela |e investigator |4 oth | |
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| 700 | 1 | |a Mohamed, Walid Ahmed Abdel Atty |e investigator |4 oth | |
| 700 | 1 | |a Rosato, Edoardo |e investigator |4 oth | |
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| 700 | 1 | |a Foti, Rosario |e investigator |4 oth | |
| 700 | 1 | |a Ancuta, Codrina |e investigator |4 oth | |
| 700 | 1 | |a Maurer, Britta |e investigator |4 oth | |
| 700 | 1 | |a Lefebvre, Paloma Garcíadela Peña |e investigator |4 oth | |
| 700 | 1 | |a Sibilia, Jean |e investigator |4 oth | |
| 700 | 1 | |a Litinsky, Ira |e investigator |4 oth | |
| 700 | 1 | |a Galdo, Francesco Del |e investigator |4 oth | |
| 700 | 1 | |a Seskute, Goda |e investigator |4 oth | |
| 700 | 1 | |a Saketkoo, Lesley Ann |e investigator |4 oth | |
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