Elsevier

Joint Bone Spine

Volume 81, Issue 1, January 2014, Pages 76-78
Joint Bone Spine

Case report
Interleukin-1 blockade in refractory giant cell arteritis

https://doi.org/10.1016/j.jbspin.2013.06.004Get rights and content

Abstract

Giant cell arteritis is a primary large-vessel vasculitis characterized by an arterial wall inflammation associated with intimal hyperplasia leading to arterial occlusion. Glucocorticoids remain the mainstay of giant cell arteritis treatment. However, relapses and glucocorticoid-related complications are frequent and therapeutic options for refractory giant cell arteritis are quite limited. Like tumor necrosis factor-α and interleukin-6, interleukin-1β is also highly expressed in inflamed arterial walls of patients with giant cell arteritis and may contribute in the pathogenesis of this disease. We report treatment of three cases of refractory giant cell arteritis successfully treated with anakinra, an interleukin-1 blockade therapy. Anakinra was effective for all patients, yielding improvement in their inflammation biomarkers and/or in their symptoms, as well as a disappearance of arterial inflammation in PET/CT for two of them.

Introduction

Glucocorticoids (GCs) remain the mainstay of treatment for giant cell arteritis (GCA). However, relapses are common when GC dosages are tapered, resulting in high cumulative doses with substantial GC-related toxicity and morbidity [1]. GCA patients refractory to GCs exhibit elevated tissue expression of the pro-inflammatory cytokines IL-1β, TNFα, and IL-6 [2] thus prompting investigators to use cytokine blockade therapy in this particular setting. TNF-blockers have failed to prove effectiveness and cannot therefore be recommended [3]. Recently, tocilizumab, an anti-IL-6 receptor therapy, has been suggested as a treatment option in refractory GCA patients [4]. However, randomized controlled trials are needed to confirm this finding. We hypothesized, on the basis of data from animal studies in which mice lacking the interleukin 1 receptor antagonist (IL-1ra) gene developed large vessel vasculitis [5], that IL-1 blockade with anakinra could be a therapeutic option in patients with GCA refractory to GCs and other steroid-sparing agents.

Section snippets

Case reports

The first patient (80-year-old male) presented in June 2005 with a 2-month history of fever of unknown origin, night sweats, weight loss and pain over his shoulder and pelvic girdle. Inflammation markers were elevated with a C-reactive protein (CRP) of 80 mg/L. A comprehensive workup including searches for an infectious disease and a whole-body CT-scan yielded normal or negative results. Temporal artery biopsy (TAB) only showed elastic internal lamina disruption. Gallium-67 scintigraphy

Discussion

Corticosteroids-sparing agents have a limited action in giant cell arteritis [6]. Methotrexate seems to show some efficacy [7]. TNF-blocking agents (infliximab and etanercept) have failed to induce and maintain disease remission [3], [8]. The efficacy of tocilizumab in naïve and refractory GCA patients has recently been demonstrated in several case series [4], [9], [10]. This anti-IL-6 receptor therapy is well tolerated in the short and medium period of treatment. However, its efficacy over a

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

We thank Dr Cornelia Wilson and Lisa Mouche for providing helpful suggestions to a previous version of the manuscript.

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