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

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 jaw pain upon mastication) * ≥1 unequivocal symptom(s) of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness * any other feature(s) judged by the clinical investigator to be consistent with GCA or PMR flares Exclusion Criteria: * 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 * History of intoxication (alcohol or medication) requiring hospitalization within 12 months before inclusion * Current chronic alcohol abuse (consumption \> 20g/day) * Recent or incoming surgery within 12 months after inclusion * History of stem cell or organ transplantation (except corneas performed more than 3 months prior inclusion) * 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: * Tocilizumab or methotrexate within 12 weeks before inclusion * Treatment with rituximab or other anti-CD20 agent within one year before inclusion * Treatment with cyclophosphamide within one year before inclusion * Hydroxychloroquine, cyclosporine A, dapsone, azathioprine, mycophenolate mofetil or janus kinase inhibitors within 4 weeks before inclusion * Tumor necrosis factor inhibitors within 8 weeks (infliximab) or 2 weeks (adalimumab or etanercept) before inclusion * Anakinra within 1 week before inclusion * Long-term systemic glucocorticoid therapy ((except dermocorticoids and inhaled corticoids) for other conditions than GCA or PMR * Patient with ≥3 prior glucocorticoid systematic therapies for another disease than GCA or PMR within the 6 months before inclusion * Long-term treatment with sulfamethoxazole/trimethoprim (Bactrim®) * Live vaccine administered within 30 days before inclusion * Laboratory abnormalities: * AST or ALT \>1.5 x upper limit of normal (ULN) * total bilirubin \>ULN * platelets\<100 G/L * leukocytes \<3 G/L * neutropenia \<1.5 G/L * lymphopenia \<0.5 G/L * haemoglobin \<8 g/dL (not related to GCA activity) * clearance of creatinine \<30 ml/min/1,73 m2 \[CKD EPI 2009\] * positive HBs antigen or positive HCV antibodies * Infections: * History of viral hepatitis B or C (chronic or acute) * HIV infection * Persistent infection or severe infection requiring hospitalization or intravenous antibiotics within 30 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration) * Proven infection requiring oral antibiotics within 14 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration) * Prior history of histoplasmosis or listeriosis * Active tuberculosis * Latent tuberculosis (diagnosis based on history of non-treated contact, opacity with a diameter greater than 1 cm on chest radiography, or positive in vitro test: Quantiferon Gold® or T-Spot-TB®). NB: a history of tuberculosis for which treatment is over and was correctly precribed regarding usual recommendations is not an exclusion criteria, whatever the results of Quantiferon Gold® or T-Spot-TB® tests. \- Unstable or poorly controlled, acute or chronic disease, not due to GCA, and which contraindicates tocilizumab or methotrexate: * Recurrent infections, unstable ischemic heart disease, renal failure (creatinine clearance \<30 ml/min/1,73 m2 \[CKD EPI 2009\]), liver failure, current liver disease, heart failure ≥ NYHA stage III/IV, respiratory failure * Neoplasia \< 5 years, (except for in situ cervical cancer and skin carcinoma, except melanoma, with R0 resection)