Effect of Adalimumab for the Treatment of Uveitis in Juvenile Idiopathic Arthritis

• Status: Completed
• Trial end date: 2015-08-27
• Target enrollment: 0
• Participant gender: All

Summary

The investigators propose to study the efficacy of adalimumab versus placebo (double-blind randomization on inclusion into 2 equal groups) on reduction of ocular inflammation quantified by laser flare photometry after two months of treatment in patients with active uveitis despite well conducted treatment with steroid eye drops and MTX. The primary objective is to demonstrate a higher response rate at 2 months in the adalimumab arm versus the placebo arm. Will be considered as responding patients those in whom the evaluated eye, 2 months after inclusion, presents at least 30% reduction of inflammation on laser flare photometry and improvement or a stable appearance on slit lamp examination. After the second month, all patients wishing to continue the trial and presenting a satisfactory clinical state will be treated with adalimumab for a total of one year after inclusion to descriptively evaluate the efficacy and safety of treatment over 10 to 12 months.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Abbott
• Treatments: Adalimumab; Antibodies; Antibodies, Monoclonal; Immunoglobulins

Criteria

Inclusion Criteria:

1. Active uveitis associated with juvenile idiopathic arthritis, with the exclusion of systemic JIA, juvenile-onset rheumatoid arthritis, and enthesitis-related JIA

2. Uveitis resistant to well conducted topical steroid therapy comprising either dexamethasone or rimexolone at a dose adapted to the patient's situation as validated by one of the investigating ophthalmologists.

3. Failure of systemic treatment with methotrexate at a dose of 0.3 to 0.6 mg.kg (without exceeding 25 mg) once a week for at least 3 months (except in the case of methotrexate intolerance).

4. Patient who can be evaluated by laser flare photometry.

5. Patient at least 4 years old on initiation of trial medication and weighing a minimum of 15 kg

6. Signed informed consent both parents and/or patient's agreement

7. Patient has a social security or similar

Exclusion Criteria:

1. Systemic JIA, juvenile-onset rheumatoid arthritis, enthesitis-related JIA (with a risk of red eye uveitis).

2. History of treatment with anti-TNF alpha monoclonal antibody (either adalimumab or infliximab).

3. Any contraindication to administration of immunosuppressive therapy (immune deficit, opportunistic infection, other severe chronic disease)

• History of cancer or lymphoproliferative disease other than successfully and completely resected squamous cell or basal cell skin cancer,

• Any uncontrolled disease: unstable diabetes with documented history of recurrent infections, unstable ischaemic heart disease, moderate to severe heart failure (NYHA stage III/IV), recent stroke and any other disease or condition inducing, in the investigator's opinion, a risk for the patient related to his/her participation in the trial,

• Positive hepatitis B or C serology indicating active infection,

• History of positive HIV serology,

• Persistent infection or severe infections requiring hospitalisation or IV antibiotic therapy during the 30 days prior to inclusion in the trial or oral antibiotic therapy during the 14 days prior to inclusion in the trial,

• History of clinically significant alcohol or other substance abuse during the previous year,

• Previous diagnosis or signs of demyelinating disease of the central nervous system,

• History of active tuberculosis, histoplasmosis or listeriosis,

• Signs of latent tuberculosis (based on a history of nontreated contamination, or an opacity greater than 1 cm on chest x-ray, or a positive intradermal reaction to 5 IU of tuberculin ≥ 5 mm).

• Negative urine pregnancy test in girls with childbearing potential

4. Chronic rupture of the blood-aqueous barrier with marked flare on the initial examination but not modified by one month of anti-inflammatory therapy.

5. Impossibility to monitor flare:

• Children < 4 years

• False flare due to the presence of giant cells on the surface of an artificial lens or in an aphakic child.

6. Children presenting complications such as refractory glaucoma or cataract rapidly requiring surgery.

7. Phthisis bulbi with hypotonia and atrophy of the ciliary body.

8. Any other situation raising problems for maintenance of stable doses of steroids and immunosuppressive drugs during the period between 4 weeks before D0 and the M2 evaluation. Authorized immunosuppressive therapies that must be maintained at stable dose are steroid eye drops, systemic steroid therapy and once weekly oral or subcutaneous MTX at a dose of 0.3 to 0.6 mg (without exceeding 25 mg).

9. Any ophthalmologic contraindication

10. If female and childbearing potential should have an appropriate contraceptive method during all study period and 5 months after last adalimumab dose. Abstinence with no oral contraception can be considered.