Clinical trial: Ustekinumab for the Treatment of Relapse of Refractory Giant Cell Arteritis (NCT03711448)

Eligibility criteria:
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 4 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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 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? Contradiction