MEthotrexate Versus TOcilizumab for Treatment of GIant Cell Arteritis: a Multicenter, Randomized, Controlled Trial

NCT03892785 | Active Not Recruiting Phase 3

• 1 other identifier: BONNOTTE PHRC N 2017
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Giant-cell arteritis (GCA) is the most frequent vasculitis after 50 years. It is characterized by a granulomatous inflammation of the wall of large vessels, involving especially the aorta and extra-cranial branches of the external carotid, with vascular remodelling leading to ischemic manifestations such as temporal headaches, jaw claudication, scalp tenderness and visual loss. Most patients with GCA also present signs of systemic inflammation, including weight loss, fatigue and fever, together with an increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Glucocorticoids (GC) are the cornerstone of the treatment of GCA. They are very effective and are usually given for 18-24 months to avoid relapses. Therefore, most patients develop GC-related complications that cause morbidity and disability. GC sparing strategies are thus required to improve the treatment of GCA.

• A 12-month treatment with tocilizumab (TCZ) has recently been shown to be effective in inducing and maintaining remission of GCA, with a dramatic GC-sparing effect. However, TCZ is an expensive drug; TCZ suppresses CRP synthesis and ESR elevation so that it is difficult to monitor patients; and importantly around 40% of patients relapse within 6 months after TCZ discontinuation, whether prescribed for 12 months or 4 months.
• In association with 6 months of prednisone, 10 mg/week of methotrexate (MTX) for 24 months lowers the risk of relapse at 24 months from 84% to 45%. Therefore, the hypothesis is that 12 months of MTX treatment (0.3 mg/Kg/week, without exceeding 20 mg/week) is not inferior to 12 months of TCZ (162 mg SC/week) in term of prevention of relapse at 18 months. The MTX strategy might be more cost effective than TCZ. In the present study, it is proposed to compare MTX versus TCZ in a multicenter randomized controlled trial. Moreover, the economic consequences associated with the use of MTX rather than TCZ will be also assess.

Conditions

Giant Cell Arteritis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients alive without relapse after initial remission or deviation from the scheduled regimen of prednisone

  Week 78

Study Arms (2)

Tocilizumab group

EXPERIMENTAL

Drug: Prednisone treatment; Drug: Tocilizumab treatment; Other: Questionnaires; Biological: Blood samples

Methotrexate group

ACTIVE COMPARATOR

Drug: Prednisone treatment; Drug: Methotrexate treatment; Other: Questionnaires; Biological: Blood samples

Interventions

Methotrexate treatment DRUG

Methotrexate subcutaneous from W0 to W51 (52 administrations). * W0: 7.5 mg/week * W1: 0.2 mg/Kg/week * W2 to W51: 0.3 mg/Kg/week (without exceeding 20 mg/week) Folic acid 10 mg/week, 48h after taking Methotrexate, from W0 to W51

Methotrexate group

Blood samples BIOLOGICAL

Additionnal blood samples for immunomonitoring

Methotrexate group; Tocilizumab group

Prednisone treatment DRUG

tapering prednisone regimen

Methotrexate group; Tocilizumab group

Tocilizumab treatment DRUG

Tocilizumab 162 mg/week subcutaneous from W0 to W51 (52 injections)

Tocilizumab group

Questionnaires OTHER

HAQ, SF-36, FACIT-fatigue

Methotrexate group; Tocilizumab 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
• Affiliation to a social security system
• Diagnosis of GCA, as defined by the revised GCA diagnosis criteria:44
• Age ≥50 years at disease onset
• AND History of erythrocyte sedimentation rate (ESR) ≥50 mm/h OR CRP≥20 mg/L (not mandatory if TAB is positive: see below)
• AND At least one of the following:
• unequivocal cranial symptoms of GCA (new onset headache, scalp tenderness, jaw claudication, temporal artery abnormality, ischemia-related vision loss)
• unequivocal symptoms of polymyalgia rheumatica (PMR)
• o AND At least one of the following:
• Temporal artery biopsy (TAB) compatible with the diagnosis of GCA (non-necrotizing vasculitis with a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells)
• Evidence of large vessel vasculitis (aorta and/or epiaortic arteries):
• angio-CT or angio-MRI: thickened arterial wall (≥2mm for the aorta and ≥1mm for epiaortic arteries) and/or contrast-enhanced arteries in T1-weighted sequences
• PET scan: grade 3 tracer uptake of the arterial wall (grade 3 = arterial SUVmax superior to the SUVmax of the liver)
• Active GCA within 6 weeks before randomization. Active GCA is defined by ESR ≥30 mm/h or CRP ≥10 mg/L and at least one of the following:
• ≥1 unequivocal cranial symptom(s) of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication)

You may not qualify if:

• Uncontrolled psychotic state
• Patient unable to give his/her consent
• Premenopausal women (menopause is defined as amenorrhea for more than 12 consecutive months)
• Non-compliant patients
• Weight\<40 Kg or \>100Kg
• Patients under maintenance of justice, wardship or legal guardianship
• Current chronic alcohol abuse (consumption \> 20g/day)
• Primary or secondary immunodeficiency
• Hypersensitivity to methotrexate or tocilizumab, one of its excipients or another human or murine monoclonal antibody
• History of diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation
• Patient refusing to sign methotrexate safety contract
• Prior treatment with any of the following:
• Long-term systemic glucocorticoid therapy ((except dermocorticoids and inhaled corticoids) for other conditions than GCA or PMR
• Long-term treatment with sulfamethoxazole/trimethoprim (Bactrim®)
• Laboratory abnormalities:

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU de Dijon

Dijon, 21079, France

Location

Related Publications (1)

• Lavergne A, Dumont A, Deshayes S, Boutemy J, Maigne G, Silva NM, Nguyen A, Gallou S, Philip R, Aouba A, de Boysson H. Efficacy and tolerance of methotrexate in a real-life monocentric cohort of patients with giant cell arteritis. Semin Arthritis Rheum. 2023 Jun;60:152192. doi: 10.1016/j.semarthrit.2023.152192. Epub 2023 Mar 20.

  PMID: 36963127 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

Surveys and Questionnaires; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: March 27, 2019
• Study Start: January 27, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

FR (1)