Chronic Disease, Uveitis
Conditions
Keywords
Adalimumab, Uveitis, Therapeutic drug monitoring
Brief summary
Uveitis and its complications are thought to account for 10 to 15% of preventable blindness in Western countries. The diagnosis of chronic non-infectious uveitis (CNUI) can be made after exclusion of pseudo uveitis or infectious uveitis, in the case of any persistent uveitis or uveitis with frequent relapses occurring less than 3 months after cessation of treatment. Adalimumab (ADA), an anti-TNFα monoclonal antibody, has marketing authorization and is widely used in the treatment of UCNI as a relay to corticosteroids. The use of ADA has been optimized, in particular through Therapeutic Drug Monitoring (TDM), based on the determination of serum ADA levels and anti-ADA antibodies. Recently, an article showed that a strategy of spacing ADA administrations in RA patients with concentrations \>8 μg/mL was not inferior to standard.
Detailed description
There is currently no formal recommendation for spacing ADA administration in patients with chronic noninfectious uveitis, but promising data from a recent retrospective study conducted by the Croix-Rousse team, led to the proposal of a decision support algorithm. Following the example of what has been shown in rheumatoid arthritis, the investigators propose to compare a strategy of spacing ADA administrations in patients with a satisfactory clinical response associated with high serum ADA concentrations.
Interventions
DIAGNOSTIC_TESTBlood sample
A blood sample will be taken, in addition to blood samples taken for the usual follow-up, with 4 dry tubes for the determination of ADA and anti-ADA antibodies and for bio-collection.
Adalimumab Injection
Sponsors
Centre Hospitalier Universitaire de Saint Etienne
Direction Générale de l'Offre de Soins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
The primary endpoint will be assessed by blinding the allocated treatment group to investigator. Thus, ophthalmological response will be assessed in a standardised manner by an ophthalmologist, blinded to the treatment strategy. The occurrence of infections will also be assessed in a manner blinded to the by an independent adjudication committee.
Intervention model description
SMOOTH is a multicenter, randomized, controlled, parallel-group, blinded end-point trial (Prospective Randomised Open, Blinded End-point, PROBE) designed to demonstrate the superiority of a TDM-based strategy of therapeutic de-escalation via the spacing of ADA administrations versus a conventional ADA-based therapeutic strategy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed and having signed the study consent form * Age ≥ 18 years * NICU according to the Standardization of Uveitis Nomenclature (SUN) criteria * Complete ophthalmological response for ≥ 48 weeks (96 weeks for uveitis related to Behçet's disease), all treatments combined * On ADA 40mg / 14 days for ≥ 24 weeks (i.e. achievement of the steady state for ADA concentrations) * Not having received systemic corticosteroid therapy for ≥ 12 weeks
Exclusion criteria
* Inability or refusal to understand and/or sign the informed consent form to participate in the study. * Inability and/or refusal to carry out the follow-up examinations required for the study. * Modification of any background immunomodulatory treatment (e.g. methotrexate, hydroxychloroquine, mycophenolate, etc.) associated with ADA, during the 12 weeks prior to inclusion. * Uveitis suspected or proven to be of infectious origin * Planned surgery (or other foreseeable medical event) requiring discontinuation of ADA for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of a complete ophthalmological response at 48 weeks | Week 48 | Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous ≤ 0.5+. |
| Infection | Week 48 | Number of infection during follow-up for up to 48 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever ≥38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of a complete ophthalmological response at 12 weeks | Weeks 12 | Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous ≤ 0.5+. |
| Maintenance of a complete ophthalmological response at 24 weeks | Weeks 24 | Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous ≤ 0.5+. |
| Maintenance of a complete ophthalmological response at 36 weeks | Weeks 36 | Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous ≤ 0.5+. |
| Infection | Week 12 | Number of infection during follow-up for up to 12 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever ≥38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee. |
| Anti-ADA antibody positivity | Weeks 12 | Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL |
Countries
France
Contacts
CONTACTLucile GRANGE, MD
CONTACTMartin KILLIAN, MD
PRINCIPAL_INVESTIGATORLucile GRANGE, MD
Centre Hospitalier Universitaire de Saint Etienne
Outcome results
None listed