Time to Relapse Following Rituximab Therapy in Rheumatoid Arthritis and Its Determinants: A Single-Center Observational Study.

BACKGROUND

Rituximab (RTX), a monoclonal antibody targeting CD20, is effective in rheumatoid arthritis (RA) refractory to conventional and biological disease-modifying antirheumatic drugs (DMARDs). However, treatment response is not always sustained, and relapse may occur after variable intervals. Time to relapse (TTR) represents the duration during which RTX maintains clinical and biological efficacy before disease recurrence.

OBJECTIVES

This study aimed to evaluate TTR after the most recent RTX cycle in patients with RA and to identify the clinical, biological, and therapeutic factors associated with its duration.

METHODS

We conducted a retro-prospective, single-center observational study including patients with RA treated with RTX between 2021 and 2025. The primary outcome was physician-assessed objective TTR following the most recent RTX cycle. Relapse-free survival was estimated using Kaplan-Meier analysis. Univariable and multivariable linear regression analyses were performed to identify clinical, biological, and treatment-related factors associated with TTR. Patient-reported relapse was collected as a secondary outcome and analyzed separately to allow comparison with physician-assessed relapse timing.

RESULTS

A total of 97 patients were included, of whom 84 (84/97, 86.6%) were female. The mean age was 57 ± 10 years, and the median disease duration was 16 years (interquartile range (IQR) 10-22). RTX was administered as retreatment in 75 patients (75/97, 77.3%) and as first-line biologic therapy in 22 patients (22/97, 22.7%). The median objective TTR was nine months (IQR 7-11), which was similar to the patient-reported TTR of 9 months (IQR 6-11). One-year flare-free survival was observed in 36 patients (36/97, 37.1%). In univariable analysis, lower baseline swollen joint count (SJC) and erythrocyte sedimentation rate (ESR) were associated with longer TTR. In multivariable analysis, only SJC remained independently associated with TTR (P = 0.040), whereas ESR showed a nonsignificant trend toward association.

CONCLUSIONS

The median TTR following RTX therapy in RA was approximately nine months. Baseline inflammatory burden, particularly SJC, emerged as the main factor associated with relapse timing, whereas RTX dose and number of treatment cycles were not significantly associated with TTR. These findings suggest that disease activity at the time of RTX administration may influence subsequent relapse timing. However, given the observational design and modest predictive performance of the final model, prospective studies are needed to confirm these observations and determine their implications for individualized retreatment strategies in RA.