Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis (ULTRA)

This is an interventional treatment trial for Patients Relapsing Refractory Giant Cell Arteritis Read More

Inclusion Criteria:

• Written consent

• Patient with GCA, defined by the following criteria (collected at the time of diagnosis of GCA):

  • Age ≥ 50 years old
  • AND sedimentation rate VS ≥ 50 mm/h or C-reactive protein CRP ≥ 20 mg/L (optional if the temporal artery biopsy (TAB) is positive)
  • AND clinical signs of GCA or signs of rhisomelic pseudopolyarthritis (RPP)
  • AND positive TAB (granulomatous vasculitis lesions) OR evidence of vasculitis of large vessels (aorta or supra-aortic trunks) by angio-TDM, PET-scanner and/or angio-MRI.
• CRP elevation >10 mg/L on at least one occasion during the 6 weeks prior to inclusion
• Relapse treatment initiated less than 6 weeks ago

• Patient with GCA relapse at a dose of prednisone ≤ 20 mg/d and who has received at least 12 consecutive weeks of corticosteroid therapy since the diagnosis of GCA. Relapse is defined as the reappearance of clinical or radiological sign(s) of GCA after a remission phase of at least 1 month AND despite well followed treatment:

  • headache (> 1 day, not relieved by paracetamol and not identical to headache that the patient may have had in the past and that is not related to GCA)
  • hyperesthesia of the scalp, claudication of the jaws or tongue, anomaly of the temporal artery
  • visual signs related to GCA
  • signs of RPP
  • non-infectious fever of more than one week
  • aggravation, recurrence or appearance of signs of vasculitis of large vessels with angioscanner, angio-MRI or PET scanner
  • any other sign related to the activity of the GCA as determined by the investigator

Exclusion Criteria:

• Person not affiliated to or not benefiting from a health insurance system
• Weight < 40kg or > 100kg (at inclusion)
• Non-compliant patient
• Adult unable to express consent
• Patient with a psychotic state not controlled by treatment
• Person subject to a measure of legal protection (curatorship, guardianship)
• Person subject to judicial control
• Women who have not gone through menopause
• Hypersensitivity to ustekinumab, to any of its excipients or to any other murine or human monoclonal antibody
• Latex hypersensitivity (because the packaging of ustekinumab contains latex, which is only present in syringes)
• Relapse with the presence of obvious ophthalmological signs requiring high-dose corticotherapy (1 mg/kg and/or methylprednisolone bolus)
• Surgery scheduled within 12 months (excluding low-risk surgery: endoscopy, bronchoscopy, hysteroscopy, cystoscopy, biopsy or breast surgery, dental care, dental extractions, eye surgery, outpatient surgery, skin surgery)
• Patient with other autoimmune or auto-inflammatory disease (except RPP, autoimmune thyroiditis, Addison's disease, type 1 diabetes, Biermer's disease and presence of autoantibodies without clinical manifestation)
• Neoplasia < 5 years (excluding in situ cervical cancer and skin carcinomas, excluding melanomas, with healthy margin resections [R0]).
• Patient who has received an organ transplant (apart from a corneal transplant)
• Patient who has received an autograft or hematopoietic marrow allograft
• Unstable or poorly controlled disease, acute or chronic, not related to GCA and considered by the investigator as a contraindication to ustekinumab treatment (examples: recurrent infections, ulcers of the lower limbs poorly controlled, unstable ischemic cardiovascular disease, terminal renal failure, liver failure, heart failure ≥ stage III/IV NYHA, diabetes poorly controlled...).

• Other treatments :

  • Patient who has received at least 3 systemic corticoid cures for a condition other than GCA within the last 6 months (dermocorticoids and inhaled corticoids are allowed)
  • Patient receiving long-term corticosteroid treatment (excluding dermocorticoids and inhaled corticosteroids) for a condition other than GCA
  • Patient currently treated or having received, within 4 weeks, cytotoxic, immunosuppressive (except methotrexate and azathioprine which should however be stopped before inclusion), immunomodulatory (except dapsone which should however be stopped before inclusion) or biotherapic treatment.
  • Live vaccine injected within 30 days of inclusion

Infections :

• Chronic (or acute) viral hepatitis B or C
• HIV infection
• Persistent infection or severe infection requiring hospitalization or intravenous antibiotic treatment within 30 days of inclusion (trial antibiotics, regardless of duration and route of administration, are not an exclusion criterion).
• Infection requiring oral antibiotic treatment within 14 days of inclusion (trial antibiotics, regardless of duration and route of administration, are not an exclusion criterion).
• History of histoplasmosis or listeriosis
• Active tuberculosis
• Sign of latent tuberculosis (based on a history of untreated contagion, an opacity greater than 1 cm in diameter on chest X-ray, or a positive in vitro test [QuantiferonR or T-spot-TBR]). A history of tuberculosis disease or latent tuberculosis whose treatment has been completed and which has been properly conducted does not constitute an exclusion criterion, regardless of the outcome of the QuantiferonR or T-spot-TBR.