Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis

NCT03711448 | Completed Phase 2

• 1 other identifier: SAMSON PHRC I 2017
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Percentage of living patients who went into remission after inclusion, without a new relapse and without deviation from the prednisone tapering protocol planned in the study.

  Week 52

Study Arms (2)

Control group

ACTIVE COMPARATOR

Drug: prednisone treatment; Other: questionnaires; Biological: Blood samples

Experimental group

EXPERIMENTAL

Drug: prednisone and ustekinumab treatment; Other: questionnaires; Biological: Blood samples

Interventions

prednisone treatment DRUG

tapering prednisone regimen

Control group

prednisone and ustekinumab treatment DRUG

Treatment with prednisone and ustekinumab (90 mg subcutaneously at inclusion (W0), W4, W16 and W28)

Experimental group

questionnaires OTHER

HAQ ; SF-36 ; FACIT-fatigue

Control group; Experimental group

Blood samples BIOLOGICAL

Additional blood samples for immunomonitoring

Control group; Experimental group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written consent
• Patient with GCA, defined by the following criteria (collected at the time of diagnosis of GCA):
• Age ≥ 50 years old
• AND sedimentation rate VS ≥ 50 mm/h or C-reactive protein CRP ≥ 20 mg/L (optional if the temporal artery biopsy (TAB) is positive)
• AND clinical signs of GCA or signs of rhisomelic pseudopolyarthritis (RPP)
• AND positive TAB (granulomatous vasculitis lesions) OR evidence of vasculitis of large vessels (aorta or supra-aortic trunks) by angio-TDM, PET-scanner and/or angio-MRI.
• Relapse treatment initiated less than 6 weeks ago
• Patient with GCA relapse at a dose of prednisone ≤ 20 mg/d and who has received at least 12 consecutive weeks of corticosteroid therapy since the diagnosis of GCA. Relapse is defined as the reappearance of clinical or radiological sign(s) of GCA after a remission phase of at least 1 month AND despite well followed treatment:
• headache (\> 1 day, not relieved by paracetamol and not identical to headache that the patient may have had in the past and that is not related to GCA)
• hyperesthesia of the scalp, claudication of the jaws or tongue, anomaly of the temporal artery
• visual signs related to GCA
• signs of RPP
• non-infectious fever of more than one week
• aggravation, recurrence or appearance of signs of vasculitis of large vessels with angioscanner, angio-MRI or PET scanner
• any other sign related to the activity of the GCA as determined by the investigator

You may not qualify if:

• Person not affiliated to or not benefiting from a health insurance system
• Non-compliant patient
• Adult unable to express consent
• Patient with a psychotic state not controlled by treatment
• Person subject to a measure of legal protection (curatorship, guardianship)
• Person subject to judicial control
• Women who have not gone through menopause
• Hypersensitivity to ustekinumab, to any of its excipients or to any other murine or human monoclonal antibody
• Latex hypersensitivity (because the packaging of ustekinumab contains latex, which is only present in syringes)
• Relapse with the presence of obvious ophthalmological signs requiring high-dose corticotherapy (1 mg/kg and/or methylprednisolone bolus)
• Surgery scheduled within 12 months (excluding low-risk surgery: endoscopy, bronchoscopy, hysteroscopy, cystoscopy, biopsy or breast surgery, dental care, dental extractions, eye surgery, outpatient surgery, skin surgery)
• Patient with other autoimmune or auto-inflammatory disease (except RPP, autoimmune thyroiditis, Addison's disease, type 1 diabetes, Biermer's disease and presence of autoantibodies without clinical manifestation)
• Neoplasia \< 5 years (excluding in situ cervical cancer and skin carcinomas, excluding melanomas, with healthy margin resections \[R0\]).
• Patient who has received an organ transplant (apart from a corneal transplant)
• Patient who has received an autograft or hematopoietic marrow allograft

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourogne

Dijon, 21000, France

Location

MeSH Terms

Interventions

Prednisone; Surveys and Questionnaires; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 18, 2018
• Study Start: January 7, 2019
• Primary Completion: September 11, 2024
• Study Completion: September 11, 2024
• Last Updated: October 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)