A recent study published in the Journal of Clinical Medicine suggests that measuring initial levels of tumor necrosis factor-alpha (TNF-α) in pediatric patients with Crohn's disease (CD) can predict their response to infliximab (IFX) treatment. The research, conducted by investigators at Samsung Medical Center, highlights the potential for personalized dosing strategies based on cytokine profiles at diagnosis.
The study enrolled 30 pediatric patients newly diagnosed with moderate-to-severe CD between June 2020 and June 2021. Researchers measured the concentrations of several cytokines, including IL-6, TNF-α, IL-17A, and IL-10, at the time of diagnosis. They then monitored the patients' clinical and biochemical remission rates, as well as IFX trough concentrations, after initiating IFX treatment.
Key Findings
The results indicated that patients who did not achieve clinical or biochemical remission had significantly higher levels of all measured cytokines (TNF-α, IL-6, IL-10, and IL-17A) at diagnosis (p < 0.05 for all). Furthermore, a negative correlation was observed between initial TNF-α concentration and IFX trough concentration (Pearson coefficient = -0.425, p = 0.034), suggesting that higher initial TNF-α levels are associated with lower IFX drug levels.
Specifically, the diagnostic capability of initial TNF-α concentration to predict under the therapeutic IFX trough concentration, defined as less than 3 µg/mL, had an area under the receiver operating characteristic of 0.730 (p = 0.049). The TNF-α concentration was set at 27.6 pg/mL as the cutoff value. The study found that if the initial TNF-α exceeds 27.6 pg/mL, the IFX trough concentration at the time of maintenance treatment may not reach the therapeutic range.
Implications for Treatment
These findings suggest that pediatric CD patients with high initial TNF-α levels may require higher doses of IFX to achieve therapeutic drug concentrations and optimal treatment outcomes. "When the initial TNF-α concentration is greater than 27.6 pg/mL, a higher dose of IFX may be more appropriate than routinely administering 5 mg/kg of IFX to maintain the therapeutic concentration," the authors noted.
The study also explored the relationships between various cytokines. IL-6, IL-10, IL-17A, and TNF-α were all found to have a statistically significant positive correlation. The highest correlation was found between IL-17A and IL-10 (Pearson correlation coefficient of 0.939, p < 0.001), followed by TNF-α and IL-10 (Pearson correlation coefficient of 0.886, p < 0.001).
Study Limitations
The authors acknowledged several limitations to their study, including the small sample size and short follow-up period. They also noted that they measured peripheral blood cytokine levels rather than tissue cytokine levels, which may provide a more accurate reflection of disease activity. Despite these limitations, the study provides valuable insights into the role of cytokines in predicting IFX response in pediatric CD patients.
Future Directions
Further research is needed to validate these findings in larger cohorts and to determine the optimal IFX dosing strategies for patients with different cytokine profiles. However, this study represents an important step towards personalized medicine in the treatment of pediatric Crohn's disease.
