Is there a clinical rationale for requiring therapeutic drug monitoring in a 17-year-old patient with chronic nonbacterial osteomyelitis and arthritis in the knees, treated with adalimumab (adalimumab, a Tumor Necrosis Factor alpha (TNF-alpha) inhibitor) on a once weekly dosing regimen?

Therapeutic Drug Monitoring for Adalimumab in Chronic Nonbacterial Osteomyelitis

For a 17-year-old patient with chronic nonbacterial osteomyelitis and knee arthritis treated with weekly adalimumab, routine proactive therapeutic drug monitoring is not recommended as there is insufficient evidence supporting its clinical benefit in this specific condition. 1

Current Evidence on Therapeutic Drug Monitoring (TDM) for Adalimumab

General Recommendations for TDM in Inflammatory Conditions

The 2024 BMJ clinical practice guideline on therapeutic drug monitoring provides the most relevant and recent evidence:

• For adalimumab maintenance therapy, there is a weak recommendation against proactive TDM due to very low-quality evidence 1
• The only evidence for critical outcomes in adalimumab TDM comes from a small trial with 78 children/adolescents, which is insufficient to recommend routine monitoring 1
• Reactive TDM (measuring levels when treatment response is inadequate) rather than proactive TDM (routine scheduled monitoring) is the more established approach 1

Specific Considerations for CNO and Juvenile Arthritis

Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that may coexist with arthritis 2. While TNF inhibitors like adalimumab are used in treatment, there are several important considerations:

• No specific guidelines exist for TDM in CNO treatment with adalimumab
• The FDA label for adalimumab notes that in juvenile idiopathic arthritis, mean steady-state trough concentrations were 6.6-8.1 mcg/mL in patients weighing ≥30 kg receiving 40 mg every other week 3
• Anti-drug antibodies can reduce serum adalimumab concentrations, but this varies by condition 3

Clinical Decision Algorithm

1. Initial Treatment Phase:

   • Begin adalimumab treatment without proactive TDM 1
   • Standard dosing for juvenile arthritis based on weight should be followed 3

2. Monitoring Approach:

   • Use reactive TDM approach (test only if inadequate response) rather than routine scheduled monitoring 1
   • Monitor clinical response through disease activity assessment

3. When to Consider Reactive TDM:

   • Primary non-response to treatment
   • Secondary loss of response after initial improvement
   • Suspected immunogenicity (development of anti-drug antibodies)
   • Unexplained adverse events

4. Laboratory Monitoring:

   • Regular monitoring of complete blood count, liver function tests, and renal function is recommended regardless of TDM 4
   • Annual tuberculosis screening is required for patients on TNF inhibitors 1

Important Caveats and Considerations

• Immunogenicity Risk: Co-administration with methotrexate reduces adalimumab clearance by 44% and decreases anti-drug antibody formation 3
• Dosing Schedule: For TNF inhibitors like adalimumab, hold for 1 dosing interval before live attenuated virus vaccines 1
• Weekly Dosing: While the patient is on weekly dosing (which is more frequent than the standard every-other-week regimen), this alone does not justify routine TDM 1
• Age Consideration: Although the patient is 17 years old (adolescent), the evidence for TDM in this age group is very limited 1

Conclusion

The current evidence does not support routine proactive therapeutic drug monitoring for adalimumab in a 17-year-old with chronic nonbacterial osteomyelitis and arthritis. A reactive approach to TDM (testing when clinically indicated by treatment failure or adverse events) is more appropriate based on current guidelines. Regular clinical monitoring of disease activity and standard safety monitoring remain essential components of care.