Evaluation of Adalimumab Tapering Strategy for Sustained Remission in Rheumatoid Arthritis Patients

The primary objective of the study is to estimate the average value of the minimal necessary **adalimumab** trough concentrations required to maintain remission in patients with rheumatoid arthritis (RA) who have been in remission for at least six months while being treated with adalimumab. This objective is clinically relevant as it aims to optimize treatment regimens by identifying the lowest effective dose, potentially reducing side effects and healthcare costs while maintaining disease control.

Secondary objectives include assessing the rate of anti-adalimumab antibodies development and tolerance in both study groups. Understanding the immunogenicity and tolerance of adalimumab is crucial for long-term treatment success and patient safety, as the presence of antibodies can affect drug efficacy and patient outcomes.

The clinical trial involves participants diagnosed with **rheumatoid arthritis** (RA) who are in remission and have been undergoing treatment with adalimumab for at least six months. The study population includes both male and female subjects over the age of 18, with no specific vulnerable populations selected. Participants are required to have achieved remission according to the DAS28 score of less than 2.6 for a minimum of six months. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must be affiliated with or beneficiaries of a social security scheme and have provided informed consent. Women of childbearing potential are required to have a negative highly sensitive pregnancy test. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants are in a stable health condition, having maintained remission with adalimumab treatment, either at a dosage of 40 mg every other week or every three weeks, according to the standard regimen.

The clinical trial is designed to evaluate an individualized biodrug tapering strategy for patients with **rheumatoid arthritis** (RA) who are in remission. The trial employs a **randomized**, **double-blind**, and **controlled** design to ensure the reliability and validity of the results. The primary objective is to estimate the minimal necessary **adalimumab** trough concentrations required to maintain remission in patients who have been in remission for at least six months. The trial is expected to last approximately two years, with an estimated end date of December 19, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis according to ACR/EULAR 2010 criteria, and ongoing adalimumab treatment. Follow-up visits will occur every three months, during which the spacing of adalimumab injections will be adjusted according to the DAS28 assessment. The presence of anti-adalimumab antibodies and tolerance, particularly regarding infections, will be monitored at each visit. The end-of-study visit will conclude the trial, assessing the primary and secondary endpoints, including the risk of RA flare and the presence of anti-adalimumab antibodies.

Participant involvement is expected to last up to 15 months, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial's methodology ensures a comprehensive evaluation of the tapering strategy's efficacy and safety, contributing valuable insights into the management of RA in patients in remission.

The clinical trial involves the administration of **adalimumab**, marketed under the name Humira, as the experimental medication. Humira is provided as a 40 mg **solution for injection** in a pre-filled syringe. The pharmaceutical form is specifically designed for **cutaneous use**, meaning it is administered via subcutaneous injection. The dosing regimen involves a maximum daily dose of 40 mg, with the total dose not exceeding 40 mg per administration. The treatment period is set to a maximum of 15 months. The administration schedule is adjusted based on the Disease Activity Score 28 (DAS28) assessment, with injections being progressively spaced out every 3 months to maintain remission in patients with rheumatoid arthritis (RA) who have been in remission for at least 6 months.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the individualized tapering strategy of adalimumab dosage. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to determine the minimal necessary adalimumab trough concentrations required to sustain remission in RA patients.

Efficacy in the clinical trial will be assessed by evaluating the relationship between the risk of **Rheumatoid Arthritis (RA)** flare and adalimumab trough concentrations. The primary endpoint involves a regression analysis to characterize this relationship. A flare-up is defined as a Disease Activity Score 28 (DAS28) increase above 2.6 for patients previously in remission (DAS28 ≤ 2.6) and a DAS28 increase (ΔDAS28) of 0.6 or greater for patients with low disease activity. The DAS28 score will be used as a validated scale to measure disease activity and remission status.

Secondary endpoints include the measurement of anti-adalimumab antibodies at each visit and during each disease flare. Tolerance will be actively monitored at each study visit, with a focus on any type of infection. Patients will document every infection in a booklet to minimize memorization bias. The study will progressively space out adalimumab injections based on DAS28 assessments conducted every three months. This approach aims to maintain remission in patients who have been in remission for at least six months while receiving adalimumab treatment.