What is the role of B cell depletion in Sjogren's (Sjögren's) syndrome?

From the Guidelines

B cell depletion therapy, primarily with rituximab, is a recommended treatment option for patients with severe, refractory systemic Sjögren's syndrome, as stated in the EULAR recommendations 1.

Key Considerations

• The standard regimen involves two 1000 mg intravenous infusions of rituximab given two weeks apart, with premedication including acetaminophen, diphenhydramine, and sometimes corticosteroids to prevent infusion reactions.
• Treatment may be repeated after 6-12 months based on clinical response.
• Patients should be screened for hepatitis B before starting therapy and monitored for infections during treatment.
• Rituximab effectively reduces B cell numbers and may improve fatigue, arthralgia, and glandular swelling in some patients, although its effects on sicca symptoms (dry eyes and mouth) are often modest.

Potential Risks and Benefits

• The use of rituximab in Sjögren's syndrome patients with ILD requires caution, as it may be associated with pneumonitis, worsening of ILD, and other potential risks 1.
• Other B cell depleting agents like belimumab or obinutuzumab may be considered in rituximab-resistant cases, though these have less established evidence in Sjögren's syndrome specifically.

Clinical Decision-Making

• The decision to use B cell depletion therapy should be individualized, taking into account the patient's disease severity, response to conventional therapies, and potential risks and benefits.
• A multidisciplinary approach involving various health professionals is essential in the management of Sjögren's syndrome patients, with a central role for specialists in autoimmune diseases 1.

From the Research

B Cell Depletion in Sjogren's Syndrome

• B cell depletion has been studied as a potential treatment for Sjogren's syndrome, with rituximab being a commonly used medication for this purpose 2, 3, 4, 5, 6.
• Rituximab therapy has been shown to be safe and effective in depleting blood B cells in patients with primary Sjögren's syndrome, although its clinical benefits have been modest 2, 5.
• 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 2.
• Sequential therapy with belimumab followed by rituximab has been shown to be effective in treating Sjögren's syndrome associated with B-cell lymphoproliferation and overexpression of BAFF 3.
• Long-term safety of rituximab in primary Sjögren syndrome has been evaluated, and it has been found to be a safe and well-tolerated treatment, with significant improvement in disease activity 5.

Mechanisms of B Cell Depletion

• B cell depletion with rituximab has been shown to increase serum BAFF levels, although no significant changes were observed in the levels of serum autoantibodies or in the blood interferon signature 2.
• The efficacy of rituximab therapy may be influenced by the overexpression of BAFF in mucosa-associated lymphoid tissue (MALT), which may decrease the efficacy of rituximab treatment in Sjögren's syndrome 3.
• Other therapeutic strategies targeting B-cell surface proteins or major cytokines of B-cell homeostasis, such as epratuzumab and anti-CD22, are being studied as potential treatments for Sjögren's syndrome 6.

Clinical Efficacy of B Cell Depletion

• Clinical trials have shown that rituximab therapy can improve subjective and objective sicca symptoms in patients with primary Sjögren's syndrome, although the results have been modest and inconsistent 2, 4, 5.
• The efficacy of rituximab therapy may be influenced by the severity and duration of the disease, as well as the presence of systemic disease 5.
• Further studies are needed to fully evaluate the clinical efficacy and safety of B cell depletion therapy in Sjögren's syndrome, and to develop reliable tools to assess disease activity and response to treatment 4, 6.