Targeting Interleukin-6 in the treatment of giant cell arteritis: hope or hype?

Abstract

Glucocorticoids still are the cornerstone in the medical treatment of giant cell arteritis (GCA), the most common form of the primary systemic vasculitides. However, recurrences are common during glucocorticoid tapering and most of the patients experience treatment-related adverse events. Glucocorticoid sparing treatment strategies at best demonstrated moderate effi cacy (methotrexate) or even failed to show a clinically signifi cant eff ect (TNFα inhibitors) [1]. According to several case series, the humanized monoclonal antibody against the Interleukin-6 receptor, tocilizumab (TCZ), could be eff ective in relieving symptoms and reducing the cumulative glucocorticoid dose in patients suff ering from GCA [1].Recently, the fi rst phase 2, randomized, double-blind, placebo-controlled trial assessing tocilizumab for induction and maintenance of remission in giant cell arteritis was published [2].This investigator initiated, single center study randomized (2:1) 30 patients with newly diagnosed or relapsing GCA fulfi lling the 1990 ACR-criteria to receive TCZ (8 mg/kg intravenously) or placebo every 4 weeks until week 52 [2]. All patients were treated with oral prednisolone, initially at a dose of 1 mg/kg/day and then rapidly tapered to 0.1 mg/kg/day at week 12. The majority (23/30) of patients had new-onset disease. The primary outcome was defi ned as the proportion of patients who achieved complete remission of disease at week 12 and was reached by 17 (85 %) of 20 patients in the TCZ-group and four (40%) of ten patients in the placebo-group (p = 0.03). Secondary effi cacy endpoints such as the relapse-free survival at week 52 (85 % vs. 20 %; p = 0.001) and the cumulative prednisolone dose at week 52 (43 mg/kg vs. 110 mg/kg; p = 0.0005) were also in favour of TCZ-treatment. At the end of the trial, prednisolone treatment could be terminated in 80% of TCZ-treated patients but only 20% of patients in the placebo-group ( p = 0.004). The overall rate of adverse events did not diff er between groups. However, infectious complications were more common in the TCZarm compared to the placebo-arm (10 episodes vs. 1 episode), and 9 episodes of neutropenia occurred in 4 patients treated with TCZ.Although the sample size is small, this well conducted study provides compelling evidence on the clinical efficacy of interleukin-6-inhibition in inducing and maintaining clinical remission in GCA. Of note, glucocorticoid tapering was performed much more rapidly than in usual clinical practice in order to reveal even small clinical eff ects of TCZ-treatment. This explains the high rate of recurrences in the placebo-group. The considerable number of infectious complications under TCZ-treatment must be considered when translating the study`s results to clinical practice.TCZ can now be regarded as the most eff ective glucocorticoid sparing agent in the treatment of GCA. Case reports also documented the feasibility of a glucocorticoidfree treatment regimen with TCZ-monotherapy [3]. However, ongoing arterial infl ammation despite clinical an...