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Comparative Study
. 2025 Apr;84(4):620-631.
doi: 10.1016/j.ard.2025.01.014. Epub 2025 Feb 1.

Post hoc comparison of the effectiveness of tocilizumab, rituximab, mycophenolate mofetil, and cyclophosphamide in patients with SSc-ILD from the EUSTAR database

Affiliations
Comparative Study

Post hoc comparison of the effectiveness of tocilizumab, rituximab, mycophenolate mofetil, and cyclophosphamide in patients with SSc-ILD from the EUSTAR database

Qingran Yan et al. Ann Rheum Dis. 2025 Apr.

Abstract

Objectives: Tocilizumab (TCZ), rituximab (RTX), mycophenolate mofetil (MMF), and cyclophosphamide (CYC) are the immunosuppressants (IS) most frequently used for systemic sclerosis-associated interstitial lung disease (SSc-ILD). This post hoc study aimed to compare their effectiveness in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database.

Methods: We included radiologically confirmed SSc-ILD patients with treatment records for TCZ, RTX, MMF, or CYC. The primary endpoint was the change in forced vital capacity (FVC) percent predicted from baseline to follow-up. Analyses were adjusted for clinical and demographic characteristics, cotreatments, and follow-up duration using propensity score-based inverse probability of treatment weighting (IPTW).

Results: Nine hundred fifty-five patients with 997 treatment observations were included in the study. The median follow-up time was 11 months (IQR, 8-14 months). After IPTW, the changes in FVC percent predicted were not significantly different in the multigroup comparison (P = .101). Paired comparisons showed no significant difference. CYC was associated with stable FVC in logistic regression. For subgroup analysis, the treatment differences in change of FVC percent predicted among the 4 groups were not significant in patients with combination IS or previous exposure to TCZ, RTX, or conventional IS, as well as in current smokers or nonsmokers, and regardless of whether observations started either at the initiating or noninitiating stage of the treatment.

Conclusions: In this first large real-world study, the effectiveness of TCZ, RTX, MMF, and CYC on FVC change in SSc-ILD patients was not statistically different.

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Conflict of interest statement

Competing interests QY: received speaker fees from Boehringer Ingelheim. ME: congress support from Janssen and AstraZeneca outside of the submitted work. CB: consultant for Boehringer Ingelheim; grant/research support from Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for Research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), and Novartis Foundation for Medical-Biological Research. Educational grants from AbbVie and the Wellcome Trust. Congress support from Boehringer Ingelheim. CM: received speaker and/or consultancy fees from Janssen-Cilag AG, Boehringer Ingelheim, MED Talks Switzerland, Medbase, Mepha, Novartis, and PlayToKnow AG, and congress support from Boehringer Ingelheim, Novartis, and Roche. RD: speakers bureau: Actelion; consultancy: Boehringer Ingelheim; grant/research support from Pfizer, Actelion, and Iten-Kohaut Foundation; congress/workshop participation support: Amgen (2022) and Otsuka (2023), unrelated to the present work. OD has/had consultancy relationship with and/or has received research funding from and/or has served as a speaker for the following companies in the area of potential treatments for SSc and its complications in the last 3 calendar years: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur, and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Cofounder of SCITU AG. The other authors declare no conflict of interest.

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