A recent study published in Clinical Rheumatology has reported that treatment with rituximab significantly reduced systemic disease activity and glucocorticoid use in patients with Sjögren’s syndrome, supporting its role as a therapeutic option for refractory systemic disease in routine clinical practice.
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune connective tissue disorder characterized by lymphocytic infiltration of exocrine glands, commonly presenting with keratoconjunctivitis sicca and xerostomia. A central pathogenic feature of the disease is B-cell hyperactivity, which has led to growing interest in therapies that selectively target B cells. Conventional treatment approaches, including glucocorticoids and disease-modifying antirheumatic drugs (DMARDs), are largely aimed at symptomatic control rather than modifying the underlying immune process. According to the 2020 recommendations from the European Alliance of Associations for Rheumatology, therapies involving monoclonal antibodies directed against B cells may be considered in patients with severe, refractory systemic disease, with rituximab being one of the key agents recommended in this context.
Rituximab is a chimeric monoclonal antibody targeting the CD20 antigen expressed on most B-cell precursors and mature B cells. Binding to CD20 leads to B-cell depletion through mechanisms including complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, thereby interfering with B-cell activation, proliferation, and differentiation. Through these mechanisms, rituximab reduces circulating B-cell populations and attenuates immune-mediated inflammation. In addition to its direct effects on B cells, emerging evidence suggests that rituximab may also influence T-cell responses, further contributing to its immunomodulatory effects in autoimmune diseases.
Although earlier randomized clinical trials did not consistently demonstrate efficacy for rituximab in primary Sjögren’s syndrome, accumulating real-world evidence has suggested potential benefits in patients with systemic disease manifestations. To further evaluate its effectiveness and safety in routine practice, investigators conducted a multicentre retrospective observational study using data from the PORTRESS. The analysis included 69 adult patients with Sjögren’s disease treated with rituximab. The study population was predominantly female (87%) with a mean age of 55.4 ± 15.1 years, and at the time of rituximab initiation, 84% of patients were receiving concomitant immunosuppressive therapy, most commonly glucocorticoids (66.7%).
Treatment with rituximab was associated with a significant reduction in systemic disease activity. The EULAR Sjögren’s Syndrome Disease Activity Index declined from a median of 11 (IQR 6–22) at baseline to 4 (IQR 0–8) at 12 months (p < 0.001), with 74% of patients achieving a clinically meaningful response defined as a reduction of at least three points in ESSDAI. Improvements were also observed in patient-reported outcomes, including reductions in the EULAR Sjögren’s Syndrome Patient Reported Index scores, along with improvements in both patient and physician global assessments.
A notable steroid-sparing effect was also observed during follow-up. The median daily glucocorticoid dose decreased from 5.0 mg (IQR 0–12.5) at baseline to 0 mg/day (IQR 0–5.0) at 12 months (p < 0.001), suggesting that rituximab therapy may help reduce long-term corticosteroid exposure in patients with active systemic disease. Rituximab demonstrated a favorable safety profile in the cohort. Mild-to-moderate adverse events were reported in 13.0% of patients. Treatment discontinuation within the first 12 months occurred in 20.3% of cases, with adverse events accounting for 7.2% of discontinuations.
The findings from this real-world multicentre cohort suggest that rituximab therapy is associated with significant reductions in systemic disease activity and glucocorticoid requirements in patients with Sjögren’s disease. These results add to the growing body of real-world evidence supporting the use of rituximab as a therapeutic option in patients with refractory systemic manifestations in routine clinical practice.
References
- Campinho Ferreira C, Bandeira M, Pereira da Costa R, Matias S, Duarte AC, Marques-Gomes C, et al. Safety and effectiveness of rituximab therapy in Sjögren’s disease: a PORTRESS – the Portuguese registry of Sjögren’s disease-based study. Clin Rheumatol. 2026 Feb;45(2):1091-1098.
- Chen YH, Wang XY, Jin X, Yang Z, Xu J. Rituximab Therapy for Primary Sjögren’s Syndrome. Front Pharmacol. 2021 Sep 2;12:731122.