P153 Rituximab and tocilizumab and their effect on lung disease progression in scleroderma: a retrospective cohort study at a single centre
Authors: Goldman Nina R , Tynan Aoife , Beesley Claire , Mageed Rizgar , Denton Christopher , Ong Voon H 
Published: April 2023

Abstract

Background/Aims
Interstitial lung disease (ILD) is one of the leading causes of death in systemic sclerosis (SSc). Evidence from randomised controlled trials suggests a beneficial effect of tocilizumab and rituximab on preserving lung function. However, comparative data outside the arena of clinical trials remains limited. Deciding when and who to treat with specific treatments remains challenging.

Methods
We performed a retrospective analysis of all SSc patients attending a single specialist centre who had received rituximab or tocilizumab. Demographic, clinical and laboratory data was collected along with serial lung function. Patients were excluded if lung function pre- and/or post-therapy was not available. Data were analysed based on anti-topoisomerase I antibody (ATA) status and other clinical, laboratory and radiological features. Wilcoxon T test and Fisher’s exact test were used.

Results
129 patients were included, of which 87 received rituximab, 32 tocilizumab and 10 both therapies. 8 of 10 (80%) patients who had received both therapies received rituximab prior to tocilizumab. 76 (58.9%) patients had diffuse SSc and 102 (79%) had ILD. Concurrent mycophenolate mofetil (MMF) was prescribed for 52 (53.6%) patients with rituximab and 17 (40.5%) patients with tocilizumab. Median pre-treatment lung function percentage forced vital capacity (%FVC) and percentage transfer factor (%DLCO) were 67.9% and 42.5% and 85.5% and 59.8% for rituximab and tocilizumab respectively. Median change %FVC and %DLCO pre- and post-treatment were +0.35% and -0.8% for rituximab and -0.9% and +0.2% for tocilizumab. Using minimally clinically important difference for change in %FVC in SSc, the majority of patients improved or remained stable (69.3% rituximab, 64.1% tocilizumab) with both treatments. A smaller percentage of patients on rituximab demonstrated FVC decline compared with tocilizumab. The effect from rituximab was not impacted by ATA status. In contrast, ATA positive patients were more likely to respond to tocilizumab (p = 0.0073) (median FVC change: tocilizumab, + 60ml ATA positive vs -110ml ATA negative; rituximab, 0ml ATA positive vs 0ml ATA negative). Disease duration and CRP had no effect on treatment response for either therapy.

Conclusion
Our retrospective cohort provides real-life data supporting the use of both rituximab and tocilizumab to stabilise ILD in SSc. Differential response based on autoantibody specificity and clinical parameters may help optimise patient selection for biological therapy in SSc-ILD. Further research to understand the exact mechanism of action driving the differential response in these patient groups is needed to greater understand the pathogenesis of SSc-ILD.
Disclosure
N.R. Goldman: Grants/research support; MRC/SRUK Clinical Research Training Fellowship [grant number MR/V030108/1]. A. Tynan: None. C. Beesley: None. R. Mageed: None. C. Denton: Consultancies; CD has been a consultant to Roche. V.H. Ong: None.