Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis
Status:
Recruiting
Trial end date:
2024-01-01
Target enrollment:
Participant gender:
Summary
Giant cell arteritis (GCA) is the most common form of vasculitis after age 50. It is a
vasculitis affecting the large vessels, in particular the aorta and its collateral vessels,
especially those in the external carotid area.
Corticosteroids are the cornerstone of GCA treatment. They are very effective but are
generally continued for 18 to 24 months or more since at least 30% of patients with GCA will
relapse during their follow-up. Thus, the vast majority of patients treated for GCA have at
least one adverse event from corticosteroid therapy, which is the main source of morbidity in
these elderly patients.
Reducing the use of corticosteroids, especially during relapses, is therefore a major
objective to improve the treatment of patients with GCA. Methotrexate, abatacept and
tocilizumab have been shown to be effective during GCA. However, the therapeutic effect of
the first two is modest. As for tocilizumab, its use has many limitations: suspensive effect,
many contraindications and there are no biological parameters available for reliable
monitoring of inflammatory syndrome in these patients.
Recent data have shown the major role of T helper (Th) Th1 and Th17 T cells in the
pathophysiology of GCA. Th17 lymphocytes are sensitive to corticosteroid therapy but Th1
persists despite treatment and produces interferon-γ which activates macrophages and smooth
muscle cells, leading to remodelling of the vascular wall responsible for ischemic GCA
manifestations. Joint targeting of Th17 and Th1 responses is therefore necessary to fully
treat the vascular inflammation that exists during GCA. Ustekinumab, which is a monoclonal
antibody blocking the subunit common to IL-12 and IL-23 (p40), blocks the Th1 and Th17
responses, and could therefore be an excellent treatment for GCA.
This study aims to evaluate the efficacy of ustekinumab for the treatment of GCA relapses.
Very little data is available on the use of ustekinumab during GCA. Recently, 14 patients
with refractory GCA, defined as the occurrence of at least 2 relapses and the inability to
reduce the prednisone dose below 10 mg/d, received ustekinumab treatment. No patients
relapsed during treatment while the median dose of prednisone was reduced from 20 to 5 mg/d.
Ustekinumab has also been used successfully in a patient with refractory GCA. Under
treatment, the patient did not have a new relapse and the dose of prednisone was reduced. In
addition, there was a major decrease in the percentages of circulating Th1 and Th17
lymphocytes.
However, to date, no controlled studies have been conducted to confirm the efficacy of
ustekinumab during GCA relapses.
This guarantees the originality and innovation of this study.