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A duo of monoclonal antibodies for Sjögren syndrome

​In a clinical trial, the IMVA-HB/IDMIT autoimmune team (UMR-S 1184 CEA/Inserm/UPSaclay/Kremlin Bicêtre Hospital) headed by Xavier Mariette has demonstrated the therapeutic benefits of the association of rituximab and belimumab for the treatment of Sjögren syndrome. Both monoclonal antibodies targeted against autoimmune diseases, the former is already marketed for forms of inflammatory arthritis and the latter for systemic lupus. The study was published in JCI Insight.

Published on 6 February 2023

Sjögren syndrome is a chronic autoimmune disease. It is characterized by lymphocytic infiltration of the salivary and lacrimal glands, resulting in buccal and ocular dryness, and multiple systemic complications associated with auto-antibody production, including an increased risk of B-cell lymphoma

About twenty years ago, Prof. Xavier Mariette's team showed the role of a cytokine, specifically B-cell activating factor (BAFF; a member of the TNF family), in B lymphocyte hyperactivation in Sjögren syndrome. Since then, the team has helped show the interest of antibodies targeted against CD20 (a B-lymphocyte surface protein) for the treatment of several autoimmune diseases. 

However, further work found that anti-CD20 treatments lead to an increase in BAFF levels, which, in turn, can lead to the stimulation of new autoreactive B lymphocytes, which, coming full circle, can reduce the efficacy of anti-CD20 therapies. This conundrum gave birth to the idea of associating two antibodies, one against CD20 and the other against BAFF, for the treatment of Sjögren syndrome.

In a recent work, Mariette's autoimmune team (UMR-S 1184 CEA/Inserm/UPSaclay/Kremlin Bicêtre) did just that, successfully deploying the strategy in patients with severe systemic complications secondary to Sjögren syndrome. These patients were treated with an association of two already market-approved monoclonal antibodies: rituximab, an anti-CD20 used in inflammatory arthritis; and belimumab, an anti-BAFF for the treatment of systemic lupus. 

As compared to each used alone, the association of the two antibodies improved therapeutic responses and especially reduced the amount of tissular B lymphocytes present in the salivary glands, one of the primary tissues affected by autoimmune infiltration in Sjögren syndrome. 

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