From the Guidelines
B cell depletion therapy, particularly rituximab, is a potentially effective treatment option for patients with moderate to severe Sjögren's syndrome who have not responded to conventional therapies. This recommendation is based on the evidence from the 2020 EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies 1. Rituximab is typically administered as two 1000 mg intravenous infusions given two weeks apart, with premedication including acetaminophen, diphenhydramine, and sometimes corticosteroids to prevent infusion reactions. The treatment may need to be repeated every 6-12 months depending on clinical response.
Key Considerations
- While not FDA-approved specifically for Sjögren's syndrome, rituximab works by targeting CD20-positive B cells, which play a central role in the pathogenesis of this autoimmune disease by producing autoantibodies, presenting antigens, and secreting pro-inflammatory cytokines 1.
- Clinical studies have shown that B cell depletion can improve symptoms such as fatigue, joint pain, and glandular function in some patients, though results are variable 1.
- Patients should be monitored for potential side effects including infusion reactions, infections, and hypogammaglobulinemia.
- Before initiating treatment, patients should undergo screening for hepatitis B, tuberculosis, and immunoglobulin levels, and live vaccines should be avoided during therapy.
Alternative Options
- Other B cell depleting agents like belimumab or newer anti-CD20 antibodies may be considered in patients who don't respond to rituximab 1.
- The EULAR recommendations also suggest the use of topical oral and ocular therapies, oral muscarinic agonists, hydroxychloroquine, oral glucocorticoids, and synthetic immunosuppressive agents in the management of Sjögren's syndrome 1.
Patient Selection
- B cell targeted therapies may be considered in patients with severe, refractory systemic disease, as stated in the EULAR recommendations 1.
- The decision to use rituximab or other B cell depleting agents should be made on a case-by-case basis, taking into account the individual patient's disease severity, response to previous treatments, and potential risks and benefits.
From the Research
B Cell Depletion and Sjogren's Syndrome
- B cell depletion has been considered a potential treatment for Sjogren's syndrome, a systemic autoimmune disease characterized by progressive exocrine gland destruction 2.
- Rituximab, a monoclonal antibody directed to CD20, has been shown to lead to transient blood B-cell depletion and has demonstrated partial improvements in subjective and objective sicca symptoms in small studies 2, 3.
- However, the results of large controlled trials are needed to confirm the efficacy of rituximab in treating Sjogren's syndrome 2, 4.
Efficacy of Rituximab
- A systematic review and meta-analysis found that rituximab had a discrete effect on improving lacrimal gland function, and potential for improving salivary flow, but no significant differences were observed in fatigue reduction, serious adverse events, quality of life improvement, and disease activity 4.
- Another study found that long-term rituximab administration was safe, well-tolerated, and effective in patients with active systemic disease, significantly reducing disease activity and controlling symptoms 5.
Mechanisms of B Cell Depletion
- B cells play a central role in the pathogenesis of primary Sjogren's syndrome, and their depletion can lead to improvements in symptoms 2, 6.
- The recovery of blood B cells following rituximab therapy is characterized by a predominance of transitional B cells and a lack of memory B cells 3.
- B-cell depletion is associated with an increase in serum BAFF levels, but no significant changes are observed in serum autoantibody levels or blood interferon signature 3.