RUBI, is the first prospective randomized, head to head study, comparing Adalimumab to either anakinra, or tocilizumab in refractory Non Infectious Uveitis (NIU). There is no firm evidence or randomized controlled trials directly addressing the best biologic agent in severe and refractory NIU. NIU can cause devastating visual loss and up to 20% of legal blindness. Corticosteroids and immunosuppressants failed to demonstrate sustainable remission over 70 % of refractory/relapsing severe uveitis. The incidence of blindness in NIU has been dramatically reduced in the recent years with the use of biologics, raising the question of whether these compounds should be used earlier in the treatment of severe non infectious uveitis. Contrasting with immunosuppressors, biotherapies act rapidly and are highly effective in steroid's sparing thus preventing occurrence of cataract and/or glaucoma. Despite a strong rationale, these compounds are not yet approved in uveitis, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
112
Anakinra (100 mg/day subcutaneously) (n=40) for 16 weeks
Tocilizumab (162 mg/7 days subcutaneously) (n=40) for 16 weeks.
Adalimumab (40mg/14 days subcutaneously) (n=40) for 16 weeks
Hopital la pitié salpetriere - Médecine interne 1
Paris, paris, France
Hopital Avicenne - CRC
Bobigny, France
Hopital Avicenne - Ophtalmologie
Bobigny, France
Hopital Avicenne- Médecine interne
Bobigny, France
Hopital Pellegrin
Bordeaux, France
Hopital Saint André - Médecine interne
Bordeaux, France
CHU Clermont-Ferrand - Hopital Gabriel Montpied - Médecine interne
Clermont-Ferrand, France
CHU Clermont-Ferrand - Hopital Gabriel Montpied - Ophtalmologie
Clermont-Ferrand, France
CHU Dijon Bourgogne -Ophtalmologie
Dijon, France
CHU Dijon Bourgogne Médecine Interne et Maladies Systémiques - Médecine 2 / SOC 2
Dijon, France
...and 17 more locations
Percentage of patients with at least 2-step reduction in Vitreous Haze (according to Miami 9-step Scale) and with a dose <= 0.1 mg/Kg/day of prednisone (or equivalent oral corticosteroid)
Percentage of patients with at least 2-step reduction in Vitreous Haze (according to Miami 9-step Scale) and with a dose \<= 0.1 mg/Kg/day of prednisone (or equivalent oral corticosteroid)
Time frame: Week 16
Mean change from baseline in Vitreous Haze
Mean change from baseline in Vitreous Haze
Time frame: Week 4, 8, 12, 16, 24
Percentage of patients with anterior chamber score = 0 or at least 2-step reduction in score (Tyndall and flare according to the Standardization of Uveitis Nomenclature (SUN) classification)
Time frame: Week 4, 8, 12, 16, 24
Mean change from baseline in BCVA (ETDRS letters score)
Time frame: Week 4, 8, 12, 16, 24
Mean change from baseline in central retinal thickness measured with Optical Coherence Tomography (OCT)
Time frame: Week 4, 8, 12, 16, 24
Percentage of patients with Central Retinal Thickness (CRT) <300 microns
Time frame: Week 4, 8, 12, 16, 24
Percentage of patients without retinal vessel leakage on fluorescein angiography
Time frame: Week 4, 8, 12, 16, 24
Percent meeting targets ≤ 0.1 mg/day prednisone
Time frame: week 16
Mean change in prednisone dose
Time frame: Week 4, 8, 12, 16, 24
Mean dose of prednisone
Time frame: week 16
Cumulative dose of prednisone
Time frame: week 16
Time to response onset
Time frame: week 16
Time to relapse of uveitis
Time frame: week 30
Number of relapse of uveitis
Time frame: week 30
Underlying systemic disease
Complete remission of extra opthalmologic sign of Behcet disease or sarcoidosis
Time frame: week 4, 8, 12, 16, 24
Percentage of adverse event
Time frame: week 4, 8, 12, 16, 24
Percentage of serious adverse event
Time frame: week 4, 8, 12, 16, 24
time to treatment failure
Time frame: week 30
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