A17: A Prospective Study Comparing Infectious Risks, Disease Activity, and Cytokine Alterations in Children with Juvenile Idiopathic Arthritis Treated with and without Tumor Necrosis Factor-alpha Inhibitors
Authors: Heather Walters, Nancy Pan, Thomas J. A. Lehman, Alexa B. Adams, Wei-Ti Huang, Lemonia Sitaras, Chahait Singh, Farzana Nuruzzaman, Sarah Taber, Susanna Cunningham-Rundles, Thomas Walsh, Sima Toussi
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Tumor necrosis factor-alpha (TNF-α) inhibitors are effective in the treatment of juvenile idiopathic arthritis (JIA), but may increase infection rates due to immunosuppression. However, as JIA results from immune system dysfunction, high disease activity may also render patients vulnerable to infection.



To our knowledge, no prior studies have prospectively evaluated whether infection rates in JIA patients vary with changes in treatment or disease activity. This study assesses infection rates in JIA patients treated with and without TNF-α inhibitors, correlates disease activity with infection risk, and explores cytokine alterations in JIA patients.



Methods:

This 12 month, prospective cohort study includes JIA subjects ages 1–21 years. TNF subjects are newly initiated on TNF-α inhibitors. Non-TNF subjects are treated without TNF-α inhibitors. At each visit, questionnaires captured mild or severe infections and treatments required. JIA disease activity (by Childhood Health Assessment Questionnaire [CHAQ] and physician joint count/global assessment) was also recorded. TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 cytokine levels were collected at pre-specified time points. Herein, we report our interim analysis of endpoints. Poisson regression and generalized estimating equations (GEE) were utilized as appropriate.



Results:

Fifty-eight subjects have been enrolled, 20 TNF and 38 non-TNF subjects (mean follow-up 7.0 and 8.6 months, respectively). We found no difference in infection rates between groups (TNF group 0.078 versus non-TNF group 0.076 infections/month, p = 0.93). No severe infections or hospitalizations occurred in either group. Numbers of physician sick visits, antimicrobial prescriptions, and missed school days related to infection were similar between groups.



Adjusting for study group and other markers of disease activity, higher joint count was associated with increased physician sick visit rates. Higher joint count and higher CHAQ were both associated with higher rates of missed school.



Cytokine serum protein analysis showed higher levels of TNF-α, IL-6, and IL-8 in TNF versus non-TNF subjects at baseline (prior to the initiation of TNF-α inhibition in TNF subjects). Subsequently, TNF-α and IL-10 were higher in TNF versus non-TNF subjects across 6 months of follow-up (p<0.05, by GEE model).



Conclusion:

Our results suggest no difference in infection rates between subjects with JIA treated with and without TNF-α inhibitors. However, some markers indicating increased disease activity (joint count and CHAQ) were associated with higher risk of secondary infectious outcomes (physician sick visits and missed school). Uncontrolled disease activity may therefore be an independent risk factor for infection that should be considered in the JIA population.



Differences in cytokine levels have been noted in our JIA subjects both before and after the initiation of TNF-α inhibition. Cytokine alterations in JIA patients should be explored further.



Ongoing analysis of the relationship between treatment changes, infection rates, disease activity, and cytokine alterations is underway to further delineate potential mechanisms and predictors of infection risk in JIA patients.