Clinical trial: Giant Cell Arteritis and Anakinra Trial (NCT02902731)

Eligibility criteria:
Minimum Age: 51 Years

        Maximum Age:

        Gender: Both Accepts Healthy Volunteers?: No

        Criteria:

        Inclusion Criteria: (Giant cell arteritis = GCA)

        Age ≥ 50 years

        Patient with temporal arteritis giant cell match 3 of the 5 criteria of the American
        College of Rheumatology (ACR) that:

        Given a temporal artery biopsy compatible with a diagnosis of GCA (not necrotizing
        arteritis, giant cell with a granulomatous inflammatory infiltrate, usually localized to
        the intima-media junction, makes lymphocytes, macrophages and multinucleated giant cells;
        or minimum detection of a chronic inflammatory infiltrate fact lymphocytes and some
        neutrophils or eosinophils without giant cells).

        Either abdominal thoracic aortitis diagnosed by:

          -  Angio CT: circumferential thickening of the aortic wall more than 3 mm, in the absence
             of adjacent plaque and active infection.

          -  MR angiography: wall thickening of the aortic wall with hyperintense on T1 weighted
             and T2 weighted enhancement after gadolinium injection.

          -  PET scanner: increased uptake of FDG by the aorta and its branches is not typical for
             GCA and may be in the atheroma. The PET scanner is probably a very sensitive technique
             but not specific enough to retain the diagnosis of GCA. We therefore consider the PET
             CT as a diagnostic method of secondary aortite the GCA if there simultaneously on the
             same exam fixing aortic (thoracic or abdominal) and blood of large caliber (artery (s)
             axillary ( s), subclavian (s) and / or carotid (s) of FDG.

        Newly diagnosed disease and from corticosteroid started up to 14 days, the initial dose is
        less or equal to1 mg / Kg or

        GCA recurrence of continuous therapy with corticosteroids (including hydroprednisone) and /
        or immunosuppression was stopped for at least 6 months. At the time of recurrence, at least
        3 of 5 ACR criteria for the diagnosis of GCA must be present. Furthermore :

          -  if BAT (Biopsy of the temporal artery) was positive at the time of initial diagnosis,
             it is not necessary to make a new.

          -  if BAT was negative, the patient can not be included after completion of a new BAT
             which will be positive or if there is a aortite, evidenced by angio-CT or MR
             angiography or PET scanner.

        For men and women of childbearing age, effective contraception must be used in the patient
        or his partner for the duration of treatment with anakinra (or placebo) and for 3 months
        after treatment. Also, breastfeeding is allowed after 3 months of stopping anakinra. Women
        considered not at risk of pregnancy are defined with menopause for at least a year or
        surgically sterile (tubal ligation, bilateral oophorectomy or hysterectomy)

        Patient wo has given its written consent Patient affiliated with a social security

        Exclusion Criteria:

        Subjects checking one of the criteria for non-inclusion may be eligible to participate in
        the research. These criteria may include:

          1. pathologies, habitus or other patient characteristics

               -  Pregnancy, breastfeeding women or women of childbearing potential not using
                  contraception

               -  dementia syndrome

               -  Patient not observing

               -  Patients who live more than 150 km from the investigation center

               -  ethyl or drug intoxication history that required hospitalization in the previous
                  year

               -  Patient monitoring and / or treated to another autoimmune disease or known
                  inflammatory

               -  Hypersensitivity to anakinra or any of its excipients (Sodium citrate (E331),
                  sodium chloride, disodium edetate (E385), polysorbate 80 (E433), sodium hydroxide
                  (E524), water for injections, substrates of origin: Escherichia coli proteins)

               -  Person under judicial protection, guardianship

               -  Person deprived of liberty

               -  Person not beneficiaries of the social security system

          2. Other therapeutic

             - Patient has already started (or stopped there less than 6 months) in a protocol or
             not frame to its ACG or another disease, treatment with anti TNF-alpha, methotrexate,
             cyclosporine, cyclophosphamide, dapsone or bolus corticosteroids.

               -  Patients on long-term glucocorticoid for another condition

               -  Early treatment of CAG disease with a dose> 1 mg / kg whatever the duration

               -  Immunization with live vaccines / mitigated during the 8 weeks

          3. Infectious diseases

               -  Chronic viral hepatitis (acute or) B or C

               -  HIV Infection

               -  Persistent infection or severe infection requiring hospitalization or treatment
                  with IV antibiotics during the 30 days prior to inclusion

               -  Infection requiring an oral antibiotic treatment in the preceding 14 days
                  inclusion

               -  History of active tuberculosis, histoplasmosis or listeriosis

               -  latent TB Signs (based on a history of untreated contagion, an opacity of greater
                  than 1 cm in diameter on chest x-ray, or an in vitro test (Quantiferon Gold or
                  T-Spot TB) positive. A history of tuberculosis disease or latent TB whose
                  treatment is completed and has been properly conducted is not an exclusion
                  criterion, whatever the result of Quantiferon or T-Spot TB.

          4. Unstable disease

               -  Uncontrolled diabetes with a history of recurrent infections

               -  unstable ischemic heart

               -  Heart failure ≥ stage III / IV NYHA

               -  Stroke recent (<6 months)

               -  Or any other severe disease resulting in the opinion of the investigator, a risk
                  to the patient due to its participation in the study.

          5. A vascular risk, metabolic, infectious, neoplastic renal or as follows:

             • Patient at high cardiovascular risk: heart disease or vascular history of proven,
             type 2 diabetes at high cardiovascular risk *, vascular risk> 20% at 10 years
             (Framingham equation) Dyslipidemia • severe uncontrolled lipid-lowering therapy

               -  Active Liver disease and liver failure

               -  Neutropenia (<1500 / mm3) at the time of the introduction of Kineret / Placebo;
                  and a patient with initial neutropenia may be included in the study if it
                  corrects under Cortancyl®, and that the experimental treatment (Anakinra-Kineret
                  / PLACEBO) may be commenced within 15 days after prednisone.

             Neoplasia under 5 years except carcinoma in situ of the cervix and skin cancer
             (excluding melanoma) with complete excision whose boundaries pass in safe area.

             • Severe renal impairment (clearance <30mL / min)

             * The high cardiovascular risk patients with diabetes are defined by:

             - A kidney disorder (proteinuria> 300mg / 24h or creatinine clearance <60mL / min
             according to Cockroft)

             - Or at least two of the following risk factors:

             - Men over 50 years, over 60 year old woman

               -  History of premature coronary disease: myocardial infarction or sudden death in
                  the father or relative in the first degree male before age 55 and before age 65
                  for females

               -  Current or quit smoking for less than 3 years

               -  High blood pressure treated or not

               -  HDL cholesterol <0.40 g / L regardless of sex

               -  Microalbuminuria (> 30 mg / 24h) NB: The moderate renal impairment (clearance ≥
                  30 mL / min and <50 mL / min) is not here a criterion for non-inclusion, but the
                  appropriate injection KINERET (anakinra) provided daily will be made every two
                  days.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 51 Years old.


Patient description (medical language): A 61-year-old man comes to the emergency department complaining of an acute vision disturbance. He had an episode of vision disturbance in the right eye that occurred suddenly and resolved spontaneously in 15 minutes. He also has right jaw pain while chewing.  He also complains of fatigue and hip muscle aches over the last several months.  The patient has a history of mild hyperlipidemia that has been controlled by diet and lifestyle modifications.  On examination, his blood pressure is 130/70 mm Hg and pulse is 66/min.  Neurological examination is unremarkable.  Visual examination is also normal. ESR is 103 mm/h. Temporal artery biopsy shows multinuclear giant cells and internal elastic membrane fragmentation.

Patient description (patient's own words): I’m a 61-year-old man and I came to the ER because I had a sudden episode where I couldn’t see out of my right eye. It only lasted about 15 minutes and went away on its own but it really scared me. I’ve also been having pain in my right jaw when I chew. For the past few months I’ve felt really tired and noticed my hips ache a lot. I have a history of mild cholesterol issues but I’ve been managing that with my diet and lifestyle. When the doctors checked me my blood pressure and pulse were normal and my vision and neurological exams didn’t show anything wrong. However they ran some tests and said my ESR levels were very high and a biopsy of my temporal artery showed some inflammation and damage.

Does the patient match the trial criteria? 1