Efficacy of Tocilizumab for the Treatment of Acute AION Related to GCA (TOCIAION)
Giant Cell Arteritis, Optic Ischaemic Neuropathy
About this trial
This is an interventional treatment trial for Giant Cell Arteritis
Eligibility Criteria
Inclusion Criteria:
- Age of 50 years or older
- Social insurance
- Diagnosis of AION, characterized by sudden and painless loss of vision, of less than one week, accompanied by pallid swelling of the optic disc
- Sudden permanent visual loss due to AION, of less than one week
Diagnosis of GCA based on the 1st (age ≥ 50 years) and the 3rd (Diagnosis of AION) criteria and at least one among the following :
- One unequivocal symptom among: New onset localized headache, scalp or temporal artery tenderness, otherwise unexplained mouth or jaw pain under mastication, or unequivocal symptoms of polymyalgia rheumatic (shoulder and/or hip girdle pain associated with inflammatory stiffness).
- Elevated erythrocyte sedimentation rate (≥ 50 at 1 hour) or C-reactive protein (≥ 10 mg/l), otherwise unexplained
- Abnormal artery biopsy Biopsy specimen with artery showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells.
- Evidence of large or medium-size vessel vasculitis at ultrasound, magnetic resonance angiography, computed tomography angiography, or positron emission tomography-computed tomography.
Exclusion Criteria:
- Other ocular involvements related to GCA (central retinal artery occlusion, posterior ischemic optic neuropathy, transient ocular manifestations, occipital stroke), if not associated with AION
- Biological targeting therapy within 3 months preceding the study
- Evidence of active infection
- History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease-free for at least 5 years
- History of recurrent infections, diverticulitis or intestinal ulceration and ASAT/ALAT > 5 * upper limit of normal, according to the Summary of Product Characteristics of tocilizumab
- Contraindication to steroids and/or aspirin administrated in the treatment
- Breastfeeding women and women with childbearing potential without highly effective contraception.
- Pregnant or nursing (lactating) women confirmed by a positive βHCG laboratory test at the inclusion
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 3 months after the last administration of tocilizumab.
- Cytopenia, as defined by platelet count < 100 × 109/L (100,000/mm3), hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L), absolute neutrophil count < 2.0 × 109/L (2000/mm3), absolute lymphocyte count < 0.5 × 109/L (500/mm3)
- Insufficient liver function (Child Pugh C )
- Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less
- Patients with previously untreated tuberculosis, previously known TDM/radiographic evidence suggestive of active and/or sequellar tuberculosis
- HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen if known before study inclusion
- Contraindication to and precaution in use of tocilizumab according to the summary product description
- Inability to provide informed consent
Sites / Locations
- CHU de Caen - Hôpital de la Côte de Nacre
- Hôpital François MitterrandRecruiting
- CHU de Limoges
- CH Montfermeil
- Centre Hospitalier National d'Ophtalmologie des Quinze-VingtsRecruiting
- Saint-Antoine HospitalRecruiting
- Pitié-Salpetrière Hospital
- Cochin HospitalRecruiting
- Fondation Rothschild,Recruiting
- Groupe Hospitalier Diaconesses-Croix Saint Simon,
Arms of the Study
Arm 1
Arm 2
Experimental
Other
tocilizumab and IV steroids combination
IV steroids combination alone
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week).
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months.