Background/Purpose:  Giant cell arteritis (GCA) is a large-vessel vasculitis usually treated with glucocorticoids (GC). GC are effective but responsible for substantial morbidity and mortality. Tocilizumab (TCZ) is a humanized monoclonal antibody against interleukin-6 receptor (IL-6R) that has recently been shown to be effective for the induction and maintenance of remission in GCA when used monthly for 1 year (1). However, data concerning the course of GCA after TCZ discontinuation are lacking and the optimal duration of this expensive immunosuppressive therapy in GCA is unknown. Our study therefore aimed to evaluate TCZ as an add-on therapy to GC during the first 3 months of GCA treatment (2).

Methods:  Patients affected by GCA, as defined by the 1990 ACR criteria and a positive temporal artery biopsy (TAB) or CT-scan or PET-scan-proven aortitis were included in this French multicenter prospective open-label study. GC were started at 0.7 mg/Kg/day and then tapered according to a standardized protocol (2) with the aim to reach 0.1 mg/Kg/day at week 24 (W24). All patients received 4 infusions of TCZ (8 mg/Kg/4 weeks) after inclusion (W0, W4, W8 and W12). The primary endpoint was the percentage of patients in remission with a dose of prednisone ≤0.1 mg/Kg/day at W26. Patients were followed for 26 weeks and data about relapses and adverse events were prospectively recorded. Quantitative data are presented as mean±SD. This trial was registered with ClinicalTrials.gov, number NCT01910038.

Results:  Twenty patients (15 women, 19 new-onset GCA) were included in this study between March 2014 and June 2015. Age at diagnosis was 72.6±7.6 years. TAB was positive in 17/19 (90%) patients and 7/16 (44%) had aortitis. Remission was obtained in all the cases, at W4 for 18/20 (90%) patients and at W8 and W12 for the two others. At W26 (14 weeks after last TCZ infusion), 5 patients (25%) had relapsed, 24.5±2.3 weeks after inclusion and at a mean dose of prednisone of 6.4±2.1 mg/day. One of these relapses was limited to a slight increase in the CRP (10 mg/L) and fibrinogen (4.6 g/L) level at W24; GC were briefly increased but the primary endpoint was reached at W26 without subsequent relapse. One patient died suddenly at W26 and was not considered to have reached the primary endpoint in the final analysis. Finally, 15 (75%) patients met the primary endpoint at W26, which is higher than previously reported with the same GC tapering i.e. 50% in the placebo group from the HECTHOR trial (2). Prednisone cumulative dose at W26 was 3,524±811 mg. After 26 weeks, 60 adverse events were reported in 19 patients and 20 were considered directly related to the study, the most common being hypercholesterolemia (n=8), infections (n=7 [3 before week 16]), and hepatic cytolysis (n=1).

Conclusion:  Four TCZ infusions as an add-on therapy to GC for GCA treatment allowed rapid GC tapering and persistent remission with a low dose of GC (0.1 mg/Kg/day) after 6 months of follow-up. However, relapses can occur after TCZ discontinuation and further studies are needed to identify predictive factor of relapse after TCZ discontinuation. REFERENCES 1. Villiger PM et al. Lancet 2016; 387:1921-7 2. Seror R et al. Ann Rheum Dis 2014; 73:2074-81.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-as-an-add-on-therapy-to-glucocorticoids-during-the-first-3-months-of-treatment-of-giant-cell-arteritis-results-of-a-french-multicenter-prospective-open-label-study/