NCT03711448

Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: Centre Hospitalier Universitaire Dijon · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Patients Relapsing Refractory Giant Cell Arteritis

Interventions

Type	Name	Description
DRUG	prednisone treatment	tapering prednisone regimen
DRUG	prednisone and ustekinumab treatment	Treatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4, W16 and W28)
OTHER	questionnaires	HAQ ; SF-36 ; FACIT-fatigue
BIOLOGICAL	Blood samples	Additional blood samples for immunomonitoring

Timeline

• Start date: 2019-01-07
• Primary completion: 2024-09-11
• Completion: 2024-09-11
• First posted: 2018-10-18
• Last updated: 2024-10-04

Locations

1 site across 1 country: France