Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis (SMOOTH)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Not yet enrolling; Phase 4

Conditions: Chronic Disease; Uveitis

Treatments: Drug: Adalimumab Injection; Diagnostic Test: Blood sample

Study type: Interventional

Funder types: Other

Identifiers

NCT06390436

2023-509733-39-00 (Other Identifier)

23PH187

Details and patient eligibility

About

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.

Full 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.

Enrollment: 320 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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320 participants in 2 patient groups

Control arm : conventional strategy

Active Comparator group

Description:

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.

Treatment:

Drug: Adalimumab Injection

Diagnostic Test: Blood sample

Arm 2: Interventional arm : adalimumab dose spacing strategy

Experimental group

Description:

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.

Treatment:

Drug: Adalimumab Injection

Diagnostic Test: Blood sample