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

Exclusion Criteria

• •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