Systemic lupus erythematosus: an expert insight into emerging therapy agents in preclinical and early clinical development

ABSTRACT

Introduction

Systemic lupus erythematosus (SLE) is a chronic disease that is potentially fatal. There is no cure for SLE and the medications used are associated with toxic side effects. In the era of revolutionary emerging novel biologic agents, the design and investigation of targeted therapy for these patients is necessary. Novel therapies under investigation in phase II–III clinical trials showed promising results. Therapies can target various pathways involved in SLE including cytokines, signal transduction inhibitors, B-cell depletion and interference with co-stimulation. Of interest is the proof of concept of sequential therapy.

Areas covered

We performed an extensive literature search via PubMed, Medline, Elsevier Science and Springer Link databases between the years 2014–2020 using the following terms: SLE, novel treatments. We have reviewed 232 articles and selected those articles that (i) focus on phase II–III emerging therapies and (ii) offer new findings from existing therapies, which reveal breakthrough concepts in SLE treatment.

Expert opinion

It is still difficult to crack the puzzle of a successful SLE treatment approach. New strategies with potential may encompass the targeting of more than one protein. Another way forward is to identify each SLE patient and personalize therapy by clinical manifestations, disease activity, serology and activated protein.

KEYWORDS:

• SLE
• novel treatment
• clinical trials
• interferon
• Jak inhibitors
• biologics
• small molecules B cell depletion

Article highlights

• Optimal SLE treatment is lacking and novel biologic therapy is lagging behind other autoimmune diseases.

• The approach to personalized medicine will include novel biomarkers from the immune system pathways, genetic and transcriptional profiles.

• Recruitment of lupus patients for new clinical trials will replace the standard of classification of SLE patients no longer grouping them by organ involvement or disease severity. Hopefully in this fashion, novel biologic agents will replace the non-specific immunosuppressing agents.

• The efficacy and safety of combination therapy with the biologic agent belimumab and standard of care treatment for SLE were demonstrated in recent trials.

• Anifrolumab, a type I interferon antagonist, is the single cytokine agent which surfaced in present clinical trials as a new potential medication for SLE, with beneficial effects in moderate to severe treatment resistant non-renal SLE.

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.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.