Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis

Inclusion Criteria:

• Written consent

• Patient with GCA, defined by the following criteria (collected at the time ofdiagnosis 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 vasculitisof large vessels (aorta or supra-aortic trunks) by angio-TDM, PET-scannerand/or angio-MRI.

• CRP elevation >10 mg/L on at least one occasion during the 6 weeks prior toinclusion

• Relapse treatment initiated less than 6 weeks ago

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

• headache (> 1 day, not relieved by paracetamol and not identical to headachethat 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 thetemporal 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 vesselswith angioscanner, angio-MRI or PET scanner

• any other sign related to the activity of the GCA as determined by theinvestigator

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 orhuman monoclonal antibody

• Latex hypersensitivity (because the packaging of ustekinumab contains latex, whichis only present in syringes)

• Relapse with the presence of obvious ophthalmological signs requiring high-dosecorticotherapy (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, autoimmunethyroiditis, Addison's disease, type 1 diabetes, Biermer's disease and presence ofautoantibodies 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 andconsidered 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 conditionother than GCA within the last 6 months (dermocorticoids and inhaled corticoidsare allowed)

• Patient receiving long-term corticosteroid treatment (excluding dermocorticoidsand 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 bestopped before inclusion), immunomodulatory (except dapsone which shouldhowever 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 intravenousantibiotic treatment within 30 days of inclusion (trial antibiotics, regardless ofduration and route of administration, are not an exclusion criterion).

• Infection requiring oral antibiotic treatment within 14 days of inclusion (trialantibiotics, regardless of duration and route of administration, are not anexclusion criterion).

• History of histoplasmosis or listeriosis

• Active tuberculosis

• Sign of latent tuberculosis (based on a history of untreated contagion, an opacitygreater 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 latenttuberculosis whose treatment has been completed and which has been properlyconducted does not constitute an exclusion criterion, regardless of the outcome ofthe QuantiferonR or T-spot-TBR.