Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement

Ki vehet részt

• Age > 60 years
• Diagnosis of
• GCA (according to ACR criteria or positive temporal artery biopsy) (de novo and/or relapse) And neurovascular involvement:
• Either Ischemic stroke (including TIA) in the vertebro-basilar or carotid territory (symptomatic arterial involvement)
• Either PET uptake of vertebral and/or carotid arteries (extra or intra cranial) and/or angioCT or angioMRI showing arterial involvement consistent with vasculitis (asymptomatic arterial involvement)
• Inclusion should be done
• within 4 weeks after the stroke concerning the "symptomatic" patients
• within 4 weeks after the diagnosis of GCA (or relapse) concerning the patients with asymptomatic neurovascular involvement
• Within 21 days after starting the corticosteroids
• Signed Informed Consent Form
• Affiliation to social security

Ki nem vehet részt

• Other proven cause of stroke: atrial fibrillation, significant atheromatous stenosis of carotid or vertebro-basilar arteries
• Contraindication to and precaution in use of tocilizumab:; Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever was longer) of screening; Previous treatment with cell-depleting therapies, including investigational agents,including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20 within 6 months before the baseline; Treatment with IV gamma globulin or plasmapheresis within 24 weeks of baseline; Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation within 2 months before the baseline; Previous treatment with TCZ within 6 months before the baseline; Immunization with a live/attenuated vaccine within 4 weeks prior to baseline or simultaneously with tocilizumab treatment; Treatment with hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil (MMF) within 4 weeks of baseline; Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab,abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline; Previous treatment with tofacitinib within 2 months before the baseline; Treatment with cyclophosphamide within 24 weeks of baseline; History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone; Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal disease; Current liver disease, as determined by the investigator; History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations; Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds); Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening; Active TB requiring treatment within the previous 3 years; Patients treated for TB with no recurrence within 3 years and patients treated for latent TB within 3 years were eligible; Primary or secondary immunodeficiency (history of or currently active); Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that had been excised and cured); History of alcohol, drug, or chemical abuse within 1 year prior to screening; Body weight >150 kg; Serum creatinine >1.4 mg/dL (124 µmol/L) in female patients and 1.6 mg/dL (141 µmol/L) in male patients; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)× 3 Upper limit of normal (ULN)>; Platelet count < 100 109/L (100,000/mm3); Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L); White blood cells <3.0 x109/L (3000/mm3); Absolute neutrophil count < 2.0 x 109/L (2000/mm3); Absolute lymphocyte count < 0.5 X 109/L (500/mm3); Positive hepatitis B surface antigen or hepatitis C antibody; Contraindication to aspirin, clopidogrel, steroids use, rifampicin and/or isoniazid; Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization, except arterial thrombectomy if necessary for ischemic stroke; Transplanted organs (except corneal transplant performed more than 3 months prior to screening); Inability to provide informed consent; Participation in another interventional research