OP0295 RITUXIMAB VERSUS TOCILIZUMAB IN PATIENTS WITH SYSTEMIC SCLEROSIS: 52-WEEK OUTCOMES OF A STRATIFIED BIOPSY-DRIVEN, OPEN-LABEL, RANDOMIZED CONTROLLED TRIAL

Background:

Systemic sclerosis is a complex autoimmune disease of unknown etiology manifested by interstitial lung disease (ILD) in 64% of patients.

Objectives:

Test the superiority of tocilizumab over rituximab in the B-cell poor population of SSc-ILD versus superiority if rituximab in B-cell rich SSc-ILD.

Methods:

This study was a 52-week, biopsy-driven, open-label, phase 4 randomized controlled trial (rituximab vs tocilizumab in patients with SSc ILD (nonresponsive to cyclophosphamide six courses of therapy), aged 20 years or older and were eligible for treatment with rituximab l. To inform balanced stratification, following a baseline lung biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) in each group to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 6 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, base line lung biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 24& 52 weeks. The primary endpoint was defined as a 50% improvement in FVC from baseline Secondary Outcome Measure: HRCT chest imaging& modified rodnan skin score. The trial is registered on the ClinicalTrials.gov ID: NCT05963048.

Results:

Between December, 2021, and June, 2023, 60 patients were classified histologically and were randomly assigned to the B-cell rich 28 patients or the B-cell poor 32 patients. In patients histologically classified as B-cell poor, there was no statistically significant difference in FVC between the rituximab group and the tocilizumab group at baseline (difference 11% [95% CI −11 to 33], p=0·31). However, in the lung biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate at 24& 52 weeks compared with the rituximab group for FVC (rituximab group [36%] of patients vs tocilizumab group [63%] of patients; difference 26% [2 to 50], p=0·035). In patients histologically classified as B-cell rich, there was no statistically significant difference in FVC between the rituximab group and the tocilizumab group at baseline p=0·52). The rituximab group had a significantly higher response rate at 24& 52 weeks compared with the tocilizumab group for FVC (rituximab group [70%] of patients vs tocilizumab group [31%] of patients; difference 22% [5 to 50], p=0·021). Occurrence of adverse events (rituximab group 7% vs tocilizumab group 10%; difference 3% [–5 to 10]) were not significantly different between treatment groups.

Conclusion:

RNA sequencing-based stratification of SSc-ILD lung tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low B-cell lineage expression signature in lung tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent large cohorts is required before making treatment recommendations for clinical practice.

REFERENCES:

NIL.

Acknowledgements:

NIL.

Disclosure of Interests:

None declared.