A Systematic Review of Anti-TNF and Anti-IL-6 Treatments for Pediatric Takayasu Arteritis: Addressing a Therapeutic Dilemma.

Abstract

Background and objectives: Takayasu arteritis (TAK) is a rare large-vessel vasculitis primarily affecting young female patients, with pediatric cases being even rarer. Biologic therapies, such as anti-tumor necrosis factor (anti-TNF) and anti-interleukin-6 (anti-IL-6) agents, have become integral to TAK treatment; however, their use in children is not well supported by robust data due to the rarity of the disease. This systematic review aimed to evaluate the use, effectiveness, and safety of anti-TNF drugs and tocilizumab in the treatment of pediatric TAK.

Methods: We conducted a systematic literature search in PubMed/MEDLINE and Scopus databases from their inception until 15 December 2024. Studies were eligible if they included pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs and reported clinical outcomes. Clinical trials, observational studies, case series, and reports were included. Data were extracted independently by two reviewers. Only English articles were analyzed. Due to heterogeneity in study designs and reporting, a narrative synthesis was performed.

Results: A total of 94 reports involving 225 pediatric patients with TAK who received 262 treatment courses of biologic treatment were included. Anti-TNF drugs were more frequently used than tocilizumab (74.2% versus 36.9%, p < 0.001). Both groups showed comparable effectiveness, with clinical improvement observed in 64.9% of anti-TNF drug and 70.9% of tocilizumab treatment courses (p = 0.438). The frequency of relapse was also similar between the two groups (~50% in both groups, p = 0.472). Hypertension was more prevalent in the anti-TNF group (p = 0.004), while concurrent glucocorticoid administration was more frequent in the tocilizumab group (p = 0.024). Infliximab was the most frequently used anti-TNF drug, with a higher proportion of patients showing improvement compared with adalimumab (71.1% versus 45.5%). Adverse events were only reported with infliximab (n = 3), including allergic and infusion reactions.

Limitations: The evidence is primarily based on case reports and series, which might have introduced selection and publication bias. Additionally, heterogeneity in diagnostic criteria, treatment protocols, and outcome definitions limits the comparability of results across studies.

Conclusion: Despite the higher frequency of anti-TNF drug use, both therapies exhibit similar clinical outcomes, highlighting the potential of tocilizumab as an equally effective alternative in pediatric TAK management. Long-term head-to-head studies are needed to optimize the data regarding biologic treatment strategies in pediatric TAK.