Adalimumab Dose Reduction Aiming Low Serum Concentration With Control of Disease Activity: a Single Blind, Non-inferiority, Randomised Clinical Trial

ADDORA-low

Several prior studies have shown that dose reduction or discontinuation of tumor necrosis factor (TNF)-inhibitors, like adalimumab, is possible in substantial number of patients with a rheumatic disease without an increase in disease activity. Prior studies showed that patients with concentrations higher than 5 mg/L are overexposed to adalimumab and can safely reduce the dose. In the first phase of treatment, an adalimumab concentration of 5mg/L is needed to achieve adequate clinical response. However to control disease activity after 28 weeks, lower concentration than 5 mg/L are probably sufficient. Recent published data suggest that concentrations of 0.1-0.5 mg/L are enough to control TNF blockade in this state. Yet, a study which investigates the lowest effective drug serum concentration is missing so far. The hypothesis is that serum adalimumab concentration of 2 mg/L is sufficient to control disease activity.

2020-03-01

2023-09-11

2023-09-11

Completed

Early phase I

78

Inclusion Criteria: * Rheumatoid arthritis patient, according to ACR 1987 or ACR/EULAR 2010 * Treated for at least 28 weeks with adalimumab * Adalimumab trough concentration \>5mg/L * Who has agreed to participate (written informed consent); * Age 18 years or older. Exclusion Criteria: * scheduled surgery during the follow-up of the study or other pre-planned reasons for treatment discontinuation * life expectancy shorter than follow-up period of the study; * other disease that might flare if adalimumab is tapered like psoriasis, inflammatory bowel disease

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patients with rheumatoid arthritis treated with adalimumab for at least 28 weeks and a serum adalimumab concentration above 5 mg/L will be randomly assigned to dose reduction by extending their dosing interval aiming a drug level of 2 mg/L or aiming a drug level of 5 mg/L', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'The participants are kept ignorant of the group to which they have been assigned', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 78, 'type': 'ACTUAL'}}

2023-11-18