An update of targeted therapeutic options for primary Sjögren syndrome: current status and future development

ABSTRACT

Introduction: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease that may affect 3 in 1,000 people within the general population. The therapeutic scenario is complex, and no therapy has proved to be able to modify the natural course of the disease, nor to prevent the most severe systemic complications.

Areas covered: Recently, the EULAR 2020 Recommendations for pSS have underlined the low level of evidence supporting efficacious therapeutic approaches, lacking a definition of specific treatment targets and being far from the ‘disease modification’ concept that is frequently used in other diseases. Herein, the authors review the status of current targeted therapies and provide the reader with their expert opinion.

Expert opinion: The progress in discovering novel treatments for pSS seem to be focused on searching new biological therapies as highly-selective drugs that can be effective without the adverse effects related to the wide, nonspecific immunosuppression induced by the drugs currently used. Most likely, the more disruptive therapeutic approach in pSS that could be seen in a few years is the use of combination strategies targeting different etiopathogenic pathways.

KEYWORDS:

• Primary sjögren syndrome
• rituximab
• b cell activating factor receptor-blocking
• abatacept
• targets cd40
• tocilizumab
• baminercept
• anakinra
• phosphatidylinositol 3-kinase delta inhibitor

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights box

• The progress in discovering novel treatments for primary Sjögren syndrome (pSS) is mainly focused on searching new biological therapies, rather than on the optimization and/or testing of synthetic immunosuppressive therapies.

• In pSS, there are 15 published RCTs that have tested a wide variety of biological therapies targeting 4 key pathogenic pathways: B-cell receptors, T-cell receptors, cytokines and kinases.

• Until now, all the promising results obtained in preliminary small studies have not been confirmed by large, well-conducted RCTs.

• Considering the number of RCTs carried out in patients with pSS, and the very poor significant results obtained so far, it is clear that the therapeutic research in pSS must be reconsidered.

• Probably, the more disruptive therapeutic approach in pSS that could be seen in a few years is the use of combination strategies targeting different etiopathogenic pathways.

Additional information

Funding

This manuscript was not funded.