Giant cell arteritis: what is new in the preclinical and early clinical development pipeline?

ABSTRACT

Introduction

Giant Cell Arteritis (GCA) is the most common systemic vasculitis worldwide. For decades, glucocorticoids have represented the mainstay of treatment, at the expense of toxic systemic effects owing to prolonged courses of high-dose treatment regimens. The search for effective drugs permitting lower glucocorticoid treatment regimens in GCA has been afrustrating one. The recent successful therapeutic application of tocilizumab, an interleukin-6 receptor inhibitor, has transformed the treatment of GCA and catalyzed research exploring other promising therapeutic targets.

Areas covered

This review explores emerging drugs in preclinical and clinical development for the management of GCA, in addition to synthesizing data on the current standard of care therapeutic agents. Drug therapies were identified by search of MEDLINE and PubMed in addition to trials from registries (clinicaltrials.gov, clinicaltrialsregister.eu, pubmed.gov) from theyear 2010.

Expert opinion

Tocilizumab has revolutionized the treatment of GCA. However, much remains to be learned about its optimal usage in GCA and asubstantial minority of pa tients do not achieve sustained glucocorticoid-free remission. Numerous exciting new agents are under investigation to fill this treatment gap in GCA, with the GM-CSF inhibitor mavrilimumab, and IL-12/23 blockade with ustekinumab providing promise through targeting the GCA pathogenic pathway in its proximal portion.

KEYWORDS:

• Giant cell arteritis
• temporal arteritis
• biologic DMARD
• DMARD
• clinical trials
• investigational drugs
• JAK inhibitor
• mavrilimumab
• tocilizumab
• Temporal Arteritis
• systemic vasculitis

Article highlights

• Giant cell arteritis (GCA) is the most common systemic vasculitis and has a propensity to cause devastating vascular complications including permanent visual loss and stroke.

• Glucocorticoids are the cornerstone of GCA treatment; however, they are associated with significant adverse events.

• The GiACTA trial demonstrated substantial efficacy of tocilizumab, a monoclonal antibody against IL-6, in the treatment of GCA.

• A significant proportion of patients do not achieve sustained glucocorticoid free remission with tocilizumab.

• Several promising therapeutic agents are in development for GCA, including mavrilimumab (GM-CSF inhibitor), ustekinumab (IL-12/23 inhibitor), and abatacept (T-cell modulator).

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

One reviewer has received honoraria/research grants from AbbVie; Amgen, Bristol-Myers Squibb; Fresenius, Lilly; MSD France; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.