Present and future of biologic drugs in primary Sjögren’s syndrome

ABSTRACT

Introduction: Primary Sjögren’s (pSS) syndrome is a chronic, autoimmune, and systemic disease characterized by xerostomia, xerophthalmia, muscle pain and fatigue. The disease may be complicated by a systemic involvement, such as a pulmonary fibrosis or the development of lymphoma which severely worsens the prognosis. Actually, there are no recommendations for the management of pSS. However, recent advances in the understanding of its pathogenesis have uncovered some pathways that have potential as therapeutic targets.

Areas covered: In this review, the authors present the biologic drugs potentially valuable to the treatment of pSS in light of its physiopathology with a ‘bird’s eye’ view of future prospects. The authors took into account relevant studies published from 2004 to 2016.

Expert opinion: Biological treatment in pSS is a promising opportunity to potentially control disease activity and prevent its complication. Currently, inhibition of B-cell and IL-17 pathways seem to be the most promising avenues. New achievements in the knowledge of pSS pathophysiology are necessary in order to try to simultaneously predict the predominant pathogenic pathway, the kind of patients at major risk to develop a more severe disease, and the appropriate biological therapy to use.

KEYWORDS:

• Biological therapy
• physiopathology
• Sjögren’s syndrome
• review

Article highlights

• Sjögren’s syndrome is a chronic and potentially severe systemic autoimmune disease, with a not clearly understood pathogenesis, but the development of biological drugs allows having a target therapy

• BAFF-APRIL pathway plays a pivotal role in the disease, and Rituximab, Belimumab and Epratuzumab showed some encouraging data. New possibilities to interfere with this pathway can be provided by Atacicept, Tabalumab, Blisibimod and Briobacept

• Modulation of T cell co-stimulation appears to be another promising way to control Sjögren’s syndrome: Abatacept shows to be safe and effective in the reduction of lymphocytic foci and in the increase of saliva production (al least in non longstanding disease), while Efalizumab causes severe adverse effects.

• Considering the intriguing role of IL-17 and chemokine in the pathogenesis of pSS, clinical trials on their respective blockers in pSS are welcomed with interest.

• In the last years, a number of biological molecules developed for the treatment of Rheumatoid Arthritis was evaluated also in the pSS treatment, taking into account the role of IL-6, IL-1 and TNF-α in Sjögren’s syndrome: a clinical trial aimed at evaluating Tocilizumab in pSS is actually ongoing, but the use of IL-1 and TNF-α blockers did not demonstrate any efficacy.

This box summarizes key points contained in the article.

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.

Additional information

Funding

This manuscript was not funded.