PO:32:176 | Outcomes of upfront combination vs monotherapy with rituximab or mycophenolate mofetil for systemic sclerosis interstitial lung disease: results from a European Scleroderma Trials and Research cohort study

Devis Benfaremo¹, Corrado Campochiaro², Gábor Kumánovics³, Christina Bergmann⁴, Elisabetta Zanatta⁵, David Launay⁶, Serena Guiducci⁷, Mickael Martin⁸, Carolina De Souza Müller⁹, Carlomaurizio Montecucco¹⁰, Luc Mouthon¹¹, Gabriella Szucs¹², Kastriot Kastrati¹³, Marie-Elise Truchetet¹⁴, Madelon Vonk¹⁵, Francesco Del Galdo¹⁶, Marco Matucci-Cerinic², Gianluca Moroncini¹, Yannick Allanore¹⁷. | ¹Department of Clinical and Molecular Sciences, Marche Polytechnic University, Marche University Hospital, Ancona, Italy; ²Vita-Salute San Raffaele University, San Raffaele Hospital, Milano, Italy; ³University of Pécs, Department Of Rheumatology And Immunology, Pécs, Hungary; ⁴University Hospital Erlangen, Department Internal Medicine 3, Erlangen, Germany; ⁵Padova University Hospital, Rheumatology Unit, Padova, Italy; ⁶Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Lille, France; ⁷University of Florence, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy; ⁸Poitiers University Hospital, Department of Internal Medicine Poitiers France; ⁹Hospital de Clinicas da Universidade Federal do Parana Curitiba Brazil; ¹⁰Università di Pavia e IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy; ¹¹Hôpital Cochin, Department of Internal Medicine, Paris, France; ¹²University of Debrecen, Faculty of Medicine, Department of Rheumatology, Debrecen, Hungary; ¹³Medical University of Vienna, Department of Medicine III, Division of Rheumatology, Vienna, Austria; ¹⁴CHU de Bordeaux, Rheumatology department, Bordeaux, France; ¹⁵Radboudumc, Department of Rheumatology Nijmegen The Netherlands; ¹⁶Leeds Raynauds and Scleroderma Program, NIHR Biomedical Research Centre, Leeds, United Kingdom; ¹⁷Université Paris Cité, Cochin Hospital, Rheumatology Department, Paris, France.

Background. Interstitial lung disease (ILD) is a major complication in systemic sclerosis (SSc) patients as it is associated with increased mortality and significant morbidity. Since combination therapies are foreseen as the future of SSc-ILD management, in this study we aimed to compare the outcomes at 12 months in patients with SSc-ILD treated with RTX alone, MMF alone, or upfront combination therapy (MMF + RTX).

Materials and Methods. SSc patients meeting the 2013 ACR/EULAR criteria, with ILD confirmed by chest HRCT and available % predicted FVC (%pFVC) at baseline and 12 ± 3 months, were eligible for inclusion. Patients were grouped based on treatment initiated at baseline: (a) MMF alone, (b) RTX alone, or (c) upfront combination therapy (MMF + RTX). Patients on nintedanib or tocilizumab at baseline were excluded. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding and treatment imbalances, following multiple imputation for missing data. Propensity score models incorporated the following variables: age, gender, disease subset (diffuse vs. limited), autoantibody status (ATA positivity), baseline FVC, and disease duration. Linear mixed-effects models were used to compare the change in %pFVC and DLCO% at 12 ± 3 months across groups. The proportion of patients with ILD progression (FVC decline >5%) was also estimated.

Results. A total of 425 patients were included in the final analysis (250 MMF, 154 RTX and 21 combination therapy). At 12 months, FVC remained stable in all treatment groups. In model 1 (MMF vs. combination), the mean change in FVC was 2.28% (95%CI 0.10 — 4.40) for MMF vs 1.83% (95%CI -2.8 — 6.5) for the combination group (mean difference -0.44, 95%CI -5.70 — 4.80, p = 0.867). The mean change in DLCO was -1.35% (95%CI -3.92 — 1.21) for MMF vs -2.05% (95%CI -11.2 — 7.14) for the combination group (mean difference -0.7, 95%CI -10.0 — 8.61, p = 0.882). In model 2 (RTX vs. combination), the mean change in FVC was -0.93% (95%CI -3.29 — 1.43) for RTX vs 1.71% (95%CI -2.97 — 6.41) for the combination group (mean difference 2.65, 95%CI -2.52 — 7.82, p = 0.315). The mean change in DLCO was -0.35% (95%CI -3.48 — 2.78) for RTX vs -1.43% (95%CI -8.6 — 5.73) for the combination group (mean difference -1.08, 95%CI -8.71 — 6.54, p = 0.781). The proportion of patients with ILD progression at 12 months was similar across treatment groups: MMF 29.2% (95%CI 23.3-35.1), RTX 28.1% (95%CI 20.2-36.0), and combination therapy 27.4% (95%CI 5.9-48.8).

Conclusions. This EUSTAR cohort analysis does not demonstrate a clear benefit of upfront combination therapy with MMF and RTX over treatment with either agent alone regarding FVC decline at 12 months in SSc-ILD patients.