Active — Not RecruitingPhase 3

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

France230 participantsStarted 2020-01-27

Plain-language 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.

Who can participate

Age range50 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * 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 j…

What they're measuring

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

Timeframe: Week 78

Trial details

NCT IDNCT03892785

SponsorCentre Hospitalier Universitaire Dijon

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-01