Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis
- Conditions
- UveitisChronic Disease
- Interventions
- Diagnostic Test: Blood sampleDrug: Adalimumab Injection
- Registration Number
- NCT06390436
- Lead Sponsor
- Centre Hospitalier Universitaire de Saint Etienne
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 320
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control arm : conventional strategy Blood sample At W0, ADA administration will be continued every 14 days. At W24, the control arm will continue to receive ADA every 14 days regardless of serum ADA concentration. Control arm : conventional strategy Adalimumab Injection At W0, ADA administration will be continued every 14 days. At W24, the control arm will continue to receive ADA every 14 days regardless of serum ADA concentration. Arm 2: Interventional arm : adalimumab dose spacing strategy Blood sample At W0, if the serum ADA concentration is ≥ 8 μg/mL, ADA administration will be spaced every 21 days. At W24, if the ADA concentration is \< 3.3 μg/mL (having a serum ADA concentration above this threshold was associated with a complete therapeutic response according to one study), administrations will be repeated every 14 days. If the ADA concentration is ≥ 3.3 and \< 8μg/mL, administrations will be left every 21 days. If ADA concentration is still ≥8μg/mL, ADA administrations will be spaced every 28 days. Arm 2: Interventional arm : adalimumab dose spacing strategy Adalimumab Injection At W0, if the serum ADA concentration is ≥ 8 μg/mL, ADA administration will be spaced every 21 days. At W24, if the ADA concentration is \< 3.3 μg/mL (having a serum ADA concentration above this threshold was associated with a complete therapeutic response according to one study), administrations will be repeated every 14 days. If the ADA concentration is ≥ 3.3 and \< 8μg/mL, administrations will be left every 21 days. If ADA concentration is still ≥8μg/mL, ADA administrations will be spaced every 28 days.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 36 Number of infection during follow-up for up to 36 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 48 Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL
Trial Locations
- Locations (11)
CH Avignon
🇫🇷Avignon, France
CH Le Puy-en-Velay
🇫🇷Le Puy-en-Velay, France
Chu Montpied
🇫🇷Clermont-Ferrand, France
CHU Grenoble Alpes
🇫🇷Grenoble, France
Hôpital de la Croix Rousse
🇫🇷Lyon, France
HCL - Hôpital Edouard Herriot
🇫🇷Lyon, France
CHU MONTPELLIER - Hôpital Saint-Eloi
🇫🇷Montpellier, France
APHP - Centre hospitalier national des Quinze-Vingts
🇫🇷Paris, France
APHP - Hôpital Cochin
🇫🇷Paris, France
APHP - Hôpital Pitié-Salpétrière
🇫🇷Paris, France
Chu de Saint-Etienne
🇫🇷Saint-Étienne, France