SYNOPSIS The giant cell arteritis (GCA) is the most frequent vasculitis in people over 50
years. Despite recent progress and physiopathogenic, corticosteroids remains the standard
treatment for decades with a very good initial clinical efficacy but a high relapse rate
(nearly 40% to 6,5 months) during its decay. This sensible population is particularly exposed
to the side effects of corticosteroids, leading to think about savings strategies. But the
association of immunosuppressive therapy and/or anti- TNFα has not demonstrated benefits in
terms of efficiency or long-term tolerance to cumulative doses of prednisone. The
responsibility of proinflammatory cytokines such as TNFα, IL- 6 and IL-1 has been studied in
the pathogenesis of GCA in temporal artery walls and in mouse models. The primary pathogenic
role of IL- 1 is based on the increase in serum or nuclear protein itself or that of its
mRNA. The study of temporal artery biopsies has shown increased local production of IL- 1β
mRNA, IL- 6 and TGFβ (indicative of macrophage activation ) and those of INFɣ and IL 2
(indicative of T lymphocyte activation). Recently, Ly et al (Ly KH JBS 2014) reported the
efficacy of anakinra, a recombinant molecule of IL- 1RA specifically blocking the IL- 1 α/β,
in three cases GCA refractory to conventional treatments.
Here investigators propose a randomized, multicenter, controlled, double-blind study of
anakinra against placebo in addition to corticosteroids in the treatment of GCA.
This study will include 70 patients randomized equally in both arms: reference treatment
(prednisone plus placebo) or the experimental treatment (prednisone + anakinra). Treatment
with prednisone will be identical in the two arms, namely a dose of 0.7 mg/kg/day orally on
day 1, followed by a progressive decrease in the dose pattern depending on the weight. In the
experimental arm, dose of anakinra is the one usually used, ie 100 mg/day by subcutaneous
injection from day 1 until the end of week 16 (S16). In the reference arm of the treatment, a
placebo anakinra is associated with corticosteroid in the same packaging, duration and
respecting the double-blind.
Investigators thus hypothesized that the addition of anakinra to corticosteroid compared to
placebo added to the latter, will show a significant decrease in GAC relapse rate. Indeed,
the challenge of corticosteroid therapy in this disease is not so much a problem of initial
effectiveness, than the adverse events related to relapses and steroid dependence.