A phase III trial evaluated the relationship between adalimumab trough levels and clinical outcomes in rheumatoid arthritis.

Conducted over 48 weeks, the study, published in RMD Open, identified a therapeutic threshold for adalimumab levels linked to improved disease control. Researchers enrolled 353 patients with active, moderate-to-severe rheumatoid arthritis (RA) who had not responded adequately to methotrexate. The participants received adalimumab (40 mg every 2 weeks) along with methotrexate. Disease activity was assessed using the Disease Activity Score (DAS28), with remission defined as DAS28-ESR < 2.6 and low disease activity (LDA) as ≤ 3.2.

Therapeutic Thresholds:

Trough levels of adalimumab ≥ 4.0 mg/L were associated with remission and LDA. Patients achieving trough levels ≥ 3.5 mg/L by week 12 had significantly higher rate of LDA at week 24 (odds ratio [OR] = 2.62, P < .001) and remission at week 48 (OR = 1.99, P = .04).

Antidrug Antibodies (ADAb):

At week 12, 15% of the participants developed ADAb, which correlated with poorer outcomes. ADAb-positive patients had lower rates of remission (4% vs 14%, P = .049) and were less likely to achieve LDA at weeks 24 and 48.

Inflammatory Markers:

Patients with adalimumab trough levels ≥ 3.5 mg/L demonstrated significantly lower median C-reactive protein (CRP) levels at weeks 24 (2.5 mg/L vs. 7.0 mg/L, P < .001) and 48 (3.0 mg/L vs 6.0 mg/L, P < .001).

Most of the participants maintained consistent drug levels within defined categories (low, middle, and high) over time. No additional clinical benefit was observed for levels exceeding 8.0 mg/L.

The findings supported therapeutic drug monitoring (TDM) as a strategy to optimize adalimumab dosing in RA. By maintaining levels ≥ 4.0 mg/L, TDM could improve disease control while reducing unnecessary dose escalation and treatment costs. However, primary nonresponse to therapy remained a concern for some patients, suggesting a need for alternative treatments.

The study’s stringent inclusion criteria may limit generalizability. Additionally, consistent methotrexate dosing across the participants precluded an analysis of dose-dependent effects on adalimumab levels.

This trial provided robust evidence to guide adalimumab dosing strategies in RA management, highlighting the potential of TDM to enhance patient outcomes. Further research is warranted to evaluate the cost-effectiveness of this approach.

Conflict of interest disclosures are available in the study.