MEthotrexate Versus TOcilizumab for Treatment of GIant Cell Arteritis: a Multicenter, Randomized, Controlled Trial (METOGiA)
Giant Cell Arteritis
About this trial
This is an interventional treatment trial for Giant Cell Arteritis
Eligibility Criteria
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)
Sites / Locations
- CHU de DijonRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Tocilizumab group
Methotrexate group