Efficacy and Safety of Anti-angiogenic Therapy With IV Bevacizumab in Patients With Symptomatic Cerebral Arteriovenous Malformations

Inclusion criteria

• Patient over 18 years of age
• With a symptomatic cerebral AVM (chronic headache, focal neurological deficit, cognitive impairment, epilepsy) of Spetzler and Martin grade III, IV or V.
• Whose symptoms are sufficiently severe to allow significant improvement with treatment:

• MoCA score ≤ 25 and/or
• NIHSS score ≥ 4 and/or
• Epilepsy Balance Score ≥ 2 and/or
• HIT-6 score ≥ 48
• With functional signs and symptoms not sequellar to a previous bleeding episode AND disabling (mRS>1)
• Ineligible for therapeutic intervention (endovascular or neurosurgery or radiosurgery)
• With normal bone marrow, liver and kidney function
• For women of childbearing potential: negative pregnancy test within 14 days of inclusion and effective contraception for up to 6 months after the end of treatment
• Having received informed consent to participate in the study
• Affiliated or beneficiary of a social security scheme

Exclusion criteria

• Known allergy to bevacizumab or an excipient.
• Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.
• Contraindication to cerebral MRI
• Absolute or relative contraindication to gadolinium injection
• Proteinuria ≥ 2+ on urine dipstick (patients with proteinuria ≥2+ on urine dipstick will need to have proteinuria ≤ 1g protein on 24-hour urine to be eligible)
• Uncontrolled hypertension (PAS >150 and/or PAD > 100 mmHg)
• History of hypertensive crisis or hypertensive encephalopathy
• Congestive heart failure (New York Heart Association Grade II or higher)
• Previous myocardial infarction or unstable angina in the preceding 12 months
• Symptomatic peripheral vascular disease
• Vascular disease (aortic aneurysm, aortic dissection)
• Major surgery, open biopsy or major traumatic lesion within 4 weeks prior to inclusion, or anticipation of the need for major surgery during the study.
• Biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to inclusion
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess in the 6 months prior to inclusion
• Significant unhealed wound, ulcer or bone fracture
• Thrombotic episode within 6 months prior to inclusion
• Atrial fibrillation
• Patient under legal protection
• Pregnant or breast-feeding women