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.
Graphical Abstract
Supplementary Information
The online version contains supplementary material available at 10.1007/s40272-025-00706-5.
Key Points
| Anti-tumor necrosis factor (anti-TNF) drugs were more frequently preferred than tocilizumab in the treatment of pediatric Takayasu arteritis (TAK) in the literature. |
| Both anti-TNF drugs and tocilizumab showed similar effectiveness and relapse frequency in pediatric TAK. |
| Infliximab was the most frequently used anti-TNF drug, with better effectiveness than adalimumab, though it was associated with some adverse reactions. |
Introduction
Takayasu arteritis (TAK) is a large vessel vasculitis characterized by granulomatous inflammation of aorta and its major branches [1]. It mainly occurs in young female patients and is much less common among children than adults [2]. The annual incidence rate of TAK ranges from 0.3 to 3.3 per million [3]. For pediatric TAK, an incidence rate of 0.4 per million children per year was reported in a Swedish study [4].
Pediatric-onset TAK differs from adult TAK in several aspects [5, 6]. While systemic hypertension at presentation and renal involvement are more frequent in children, complete vessel occlusion and claudication are more common in adults [5, 6]. Both large comparative studies of adult and pediatric TAK highlighted that childhood TAK is associated with more pronounced inflammation [5, 6]. In addition to influencing the frequency of systematic symptoms such as fever and fatigue, this feature may also affect the response to various immunosuppressive agents including biologics. Whether the difference in the degree of inflammation reflects an underlying difference in disease pathogenesis remains to be elucidated.
High-dose glucocorticoids and early introduction of glucocorticoid-sparing disease-modifying anti-rheumatic drugs (DMARDs) form the mainstay of TAK treatment [2]. TAK management in children is mainly driven by the data from adult studies. With the improved understanding of inflammation dynamics in TAK, biologic drugs targeting tumor necrosis factor (TNF), interleukin 6 (IL-6), and even Janus kinase (JAK) inhibitors are included in the treatment [7, 8]. Adverse events such as cytotoxicity and infertility associated with cyclophosphamide, which was traditionally the main treatment of severe TAK, have prompted a shift to biologic treatments. Biologic drugs are included in recent therapeutic guidelines for TAK [8–10]. In the AHA [10] and EULAR [9] guidelines, no preference was stated between anti-TNF drugs or anti-IL-6, while anti-TNF treatment was preferred over anti-IL-6 in the ACR 2021 guideline [8]. A recent systematic literature review and meta-analysis including reports of > 5 patients identified similar frequencies of clinical remission, angiographic stabilization, and adverse events with anti-TNF drugs and tocilizumab [11].
In this review, we aimed to analyze the data regarding anti-TNF drug and tocilizumab use in children with TAK. Considering the rare occurrence of TAK in children and the scarcity of controlled studies in the pediatric population, we also included data from case reports and case series.
Methods
Search Strategy
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [12], the PubMed/MEDLINE and Scopus databases were reviewed independently by both authors (E.D.B. and S.S.) without any restrictions of date until 15 December 2024. The keywords for literature search were determined by combining the disease name “Takayasu arteritis” with “tumor necrosis factor alpha inhibitors,” “anti-tumor necrosis factor alpha,” “anti-TNF,” “TNF inhibitors,” "etanercept,” “adalimumab,” “infliximab,” “certolizumab," “golimumab,” “anti-interleukin-6,” “anti-IL-6,” “interleukin-6 inhibitors,” and “tocilizumab.” In the search, Medical Subject Headings (MeSH) and Boolean operators “AND” and “OR” were also used. The complete list of the search terms is provided in the Supplementary Table 1. After removing duplications, articles were screened to exclude reports that did not meet inclusions criteria.
Inclusion and Exclusion Criteria
All reports (including single-case reports) that presented data on pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs were included. Only English articles were analyzed.
The following types of studies and reports were excluded from this systematic review: in vitro studies, animal studies (including in vivo models), in silico studies, editorials, conference abstracts or proceedings, clinical guidelines, commentaries, book chapters, and any studies that did not report on pediatric patients with TAK treated with anti-TNF or anto-IL-6 drugs.
Data Collection
The data regarding demographic features, clinical characteristics, type of biologic treatment, treatment duration, response, relapse under biologic treatment, and adverse events were extracted from the included articles. Where available, data on surgical interventions, organ damage, and mortality were also collected to assess long-term outcomes. Discrepancies in data extraction were resolved by discussion between the two authors.
Quality Assessment
The methodological quality of the randomized controlled trial included in this review (the TAKT study) was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool [13]. The included observational studies were evaluated using the Newcastle-Ottawa Scale (NOS) [14]. For studies without a comparison group that included three or more patients (case series), the Joanna Briggs Institute (JBI) critical appraisal checklist for case series was used [15].
Statistical Analysis
All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize demographic and clinical characteristics of the patients, as well as the frequency and outcomes of biologic treatments. Categorical variables were compared using chi-squared or Fisher’s exact test, where appropriate. Continuous variables were presented as median (interquartile range, IQR), and comparisons between groups were performed using the Mann–Whitney U test. A p-value of < 0.05 was considered statistically significant.
Results of the Systematic Literature Review
A total of 94 reports involving 225 pediatric patients with TAK treated with tocilizumab or an anti-TNF drug were included (Fig. 1) [1, 5, 16–107]. Among these reports, there were 11 uncontrolled observational studies, 1 randomized controlled study, 9 case series, and 73 case reports. The quality assessments of the included reports (except for case reports) are presented in Supplementary Tables 2, 3, and 4. The data of 107 patients were derived from reports that included fewer than 5 patients. The details of the extracted data from included articles are presented in Supplementary Table 5.
Fig. 1.
PRISMA flow diagram of literature screening regarding patients with pediatric Takayasu arteritis treated with anti-tumor necrosis factor (TNF) or anti-interleukin-6 (IL-6) drugs. *Others: letter, editorial, conference paper, guideline, comment, note, short survey. IL, interleukin; TAK, Takayasu arteritis; TNF, tumor necrosis factor
The median (IQR) age at diagnosis was 12 (4.8) years, and 78% of the patients were female. The most common clinical findings at presentation included constitutional symptoms (73.7%) followed by cardiovascular manifestations (60.1%). Hypertension was reported in 20.9% of cases, with a significantly higher prevalence in the anti-TNF group compared with the tocilizumab group (p = 0.004). Elevated acute phase reactants were observed in almost all patients (98.5%). Radiologically, the most frequently involved regions were the abdominal aorta (56.6%) and common carotid arteries (43.4%). Most patients received concomitant glucocorticoids (84.3%) and methotrexate (41.4%) during biologic treatment.
The definitions of remission and relapse were not consistently available across all articles, and when provided, they were not standardized. The definitions in the included articles (randomized controlled trial, observational studies, and case series) are summarized in Supplementary Table 6. Complete clinical response, partial clinical response, or any mention of improvement in disease activity were all categorized as “improvement.” Conversely, reports of disease progression or lack of improvement were categorized as “no improvement.”
The number of biologic treatments overall was 262 for 225 patients, as 30 patients received 2 different biologics, 2 patients received 3 different biologics, and 1 patient received 4 different biologic drugs each, among different anti-TNF drugs or tocilizumab (Table 1); 25 patients used both anti-TNF drugs and tocilizumab at different timepoints.
Table 1.
Features of pediatric patients in the literature with Takayasu arteritis treated with anti-tumor necrosis factor (TNF) or anti-interleukin-6 (IL-6) drugs
| Variables | All patients | Patients treated with anti-TNF | Patients treated with anti-IL-6 | p-value |
|---|---|---|---|---|
| Number of patientsa, median (IQR) | 225 | 167 (74.2) | 83 (36.9) | < 0.001 |
| Number of biologic treatments, n (%) | 262 | 179 (68.3) | 83 (31.7) | < 0.001 |
| Age at diagnosis, years, median (IQR) | 12 (4.8) | 11 (3.9) | 14 (5.1) | 0.209 |
| Sex, female, n (%) | 117/150 (78) | 72/96 (75) | 45/54 (83.3) | 0.237 |
| Clinical findings, n (%) | ||||
| Constitutional findings | 112/152 (73.7) | 72/100 (72) | 40/52 (76.9) | 0.513 |
| Mucocutaneous findings | 34/143 (23.8) | 22/98 (22.4) | 12/45 (26.7) | 0.582 |
| Cardiovascular findings | 86/143 (60.1) | 58/98 (59.2) | 28/45 (62.2) | 0.730 |
| Hypertension | 30/143 (20.9) | 27/98 (27.6) | 3/45 (6.7) | 0.004 |
| Absence or weakness of the pulses | 38/143 (26.6) | 25/98 (25.5) | 13/45 (28.9) | 0.671 |
| BP differences between extremities | 30/143 (20.9) | 17/98 (17.3) | 13/45 (28.9) | 0.115 |
| Vascular murmur | 32/143 (22.4) | 21/98 (21.4) | 11/45 (24.4) | 0.698 |
| Claudication | 11/143 (7.7) | 5/98 (5.1) | 6/45 (13.3) | 0.086 |
| Others | 11/143 (7.7) | 5/98 (5.1) | 6/45 (13.3) | 0.086 |
| GIS findings | 28/143 (19.6) | 21/98 (21.4) | 7/45 (15.6) | 0.411 |
| Neurologic symptoms | 12/143 (8.4) | 9/98 (9.2) | 3/45 (6.7) | 0.614 |
| Respiratory symptoms | 4/143 (2.8) | 4/98 (4.1) | 0 | – |
| Elevated APR, n (%) | 134/136 (98.5) | 85/86 (98.8) | 49/50 (98) | 0.696 |
| Radiologic findings, n (%) | ||||
| Internal carotid arteries | 7/143 (4.9) | 6/91 (6.6) | 1/52 (1.9) | 0.213 |
| Common carotid arteries | 62/143 (43.4) | 39/91 (42.9) | 23/52 (44.2) | 0.873 |
| Vertebral artery | 10/143 (6.9) | 7/91 (7.7) | 3/52 (5.8) | 0.664 |
| Brachiocephalic trunk | 16/143 (11.1) | 10/91 (10.9) | 6/52 (11.5) | 0.920 |
| Subclavian arteries | 55/143 (38.5) | 35/91 (38.5) | 20/52 (38.5) | 1.000 |
| Axillary artery | 13/143 (9.1) | 11/91 (12.1) | 2/52 (3.8) | 0.099 |
| Ascending aorta | 50/143 (34.9) | 37/91 (40.7) | 13/52 (25) | 0.059 |
| Aortic arch | 38/143 (26.6) | 23/91 (25.3) | 15/52 (28.8) | 0.642 |
| Coronary arteries | 27/143 (18.9) | 17/91 (18.7) | 10/52 (19.2) | 0.936 |
| Pulmonary arteries | 13/143 (9.1) | 10/91 (10.9) | 3/52 (5.8) | 0.296 |
| Descending thoracic aorta | 57/143 (39.9) | 40/91 (43.9) | 17/52 (32.7) | 0.186 |
| Abdominal aorta | 81/143 (56.6) | 54/91 (59.3) | 27/52 (51.9) | 0.389 |
| Celiac trunk | 13/143 (9.1) | 10/91 (10.9) | 3/52 (5.8) | 0.296 |
| Gastroduodenal artery | 1/143 (0.7) | 1/91 (1.1) | 0 | – |
| Superior mesenteric arteries | 39/143 (27.3) | 29/91 (31.9) | 10/52 (19.2) | 0.103 |
| Renal arteries | 45/143 (31.5) | 28/91 (30.8) | 17/52 (32.7) | 0.812 |
| Inferior mesenteric arteries | 3/143 (2.1) | 3/91 (3.3) | 0 | – |
| Common iliac arteries | 5/143 (4.5) | 5/91 (5.5) | 0 | – |
| External iliac artery | 1/143 (0.7) | 1/91 (1.1) | 0 | – |
| Common femoral arteries | 9/143 (6.3) | 5/91 (5.5) | 4/52 (7.7) | 0.160 |
| Types of biologic drugs, n (%) | ||||
| Anti-TNF drugs | 179 (68.3) | 179 (100) | 0 | – |
| ADA | 27 (10.3) | 27 (15.1) | 0 | – |
| ETN | 6 (2.3) | 6 (3.4) | 0 | – |
| IFX | 136 (51.9) | 136 (75.9) | 0 | – |
| Golimumab | 2 (0.8) | 2 (1.1) | 0 | – |
| Not specified | 8 (3.1) | 8 (4.5) | 0 | – |
| Tocilizumab | 83 (31.7) | 0 | 83 (100) | – |
| Concomitant immunosuppressive treatments, n (%) | ||||
| Glucocorticoid | 167/198 (84.3) | 111/137 (81.1) | 57/61 (93.4) | 0.024 |
| Any conventional DMARD | 108/198 (54.5) | 79/137 (57.7) | 29/61 (47.5) | 0.187 |
| Azathioprine | 10/139 (7.2) | 7/137 (5.1) | 3/61 (4.9) | 1.000 |
| Cyclophosphamide | 6/198 (3.1) | 4/137 (2.9) | 2/61 (3.3) | 1.000 |
| Methotrexate | 82/198 (41.4) | 62/137 (45.3) | 20/61 (32.8) | 0.100 |
| Mycophenolate mofetil | 12/198 (6.1) | 6/137 (4.4) | 6/61 (9.7) | 0.194 |
| Tacrolimus | 5/198 (2.5) | 3/137 (2.2) | 2/61 (3.3) | 0.645 |
| Previous treatments, n (%) | ||||
| Anakinra | 2/191 (0.5) | 1/125 (0.8) | 1/66 (1.5) | 1.000 |
| Glucocorticoid | 163/191 (85.3) | 103/125 (82.4) | 60/66 (90.9) | 0.114 |
| IVIG | 12/191 (6.3) | 9/125 (7.2) | 3/66 (4.5) | 0.549 |
| Rituximab | 1/191 (0.5) | 0 | 1/66 (1.5) | – |
| Any conventional DMARD | 148/202 (73.3) | 103/136 (75.7) | 45/66 (68.2) | 0.255 |
| Azathioprine | 29/191 (15.2) | 23/125 (18.4) | 6/66 (9.1) | 0.088 |
| Colchicine | 2/191 (1.1) | 2/125 (1.6) | 0 | – |
| Cyclophosphamide | 66/202 (32.7) | 46/136 (33.8) | 20/66 (30.3) | 0.617 |
| Cyclosporine A | 5/191 (2.6) | 4/125 (3.2) | 1/66 (1.5) | 0.661 |
| Dapsone | 2/191 (1.1) | 2/125 (1.6) | 0 | – |
| Methotrexate | 85/191 (44.5) | 61/125 (48.8) | 24/66 (36.4) | 0.100 |
| Mizoribine | 2/191 (1.1) | 0 | 2/66 (3.1) | – |
| Mycophenolate mofetil | 11/191 (5.8) | 7/125 (5.6) | 4/66 (6.1) | 1.000 |
| Tacrolimus | 8/191 (4.2) | 4/125 (3.2) | 4/66 (6.1) | 0.451 |
| Active disease before biologic treatment, n (%) | 117/129 (90.7) | 65/75 (86.7) | 52/54 (96.3) | 0.063 |
| Disease duration before biologic treatment, months, median (IQR) | 11 (15) | 12 (16) | 10.5 (13.5) | 0.319 |
| Duration of biologic treatment, months, median (IQR) | 12 (15.6) | 12 (16.2) | 12 (14.8) | 0.966 |
| Duration of follow-up, years, median (IQR) | 2.6 (6.4) | 3 (8.1) | 2.1 (4.8) | 0.566 |
| Relapse under biologic drugs, n (%) | 32/60 (53.3) | 21/39 (53.8) | 10/21 (47.6) | 0.472 |
| Duration of remission before relapseb, median (IQR) | 12 (12.75) | 12 (8) | 13 (19.5) | 0.647 |
| Response to biologic drugs, n (%) | ||||
| Improvement | 113/169 (66.9) | 74/114 (64.9) | 39/55 (70.9) | 0.438 |
| No improvement | 56/169 (33.1) | 40/114 (35.1) | 16/55 (29.1) | 0.438 |
| Adverse event due to biologic use, n (%) | 3/26 (11.5) | 3/18 (16.7) | 0/8 | – |
| Outcome | ||||
| Organ damage | 11/143 (7.7) | 6/98 (6.1) | 5/45 (11.1) | 0.109 |
| Heart failure | 7/143 (4.9) | 5/98 (5.1) | 2/45 (4.4) | 0.760 |
| Ischemic stroke | 2/143 (1.4) | 1/98 (1.1) | 1/45 (2.2) | 0.254 |
| Renal failure | 1/143 (0.8) | 0 | 1/45 (2.2) | - |
| Visual loss | 1/143 (0.8) | 0 | 1/45 (2.2) | - |
| Surgical interventions | 16/191 (8.4) | 13/125 (10.4) | 3/66 (4.5) | 0.165 |
| Mortality | 5/169 (2.9) | 3/114 (2.6) | 2/55 (3.6) | 0.891 |
APR, acute phase reactants; BP, blood pressure; DMARD, disease-modifying antirheumatic drug; ETN, etanercept; GIS, gastrointestinal system; IFX, infliximab; IVIG, intravenous immunoglobulin; TNF, tumor necrosis factor
aA total of 25 patients received both anti-TNF and tocilizumab treatment.
bThe duration of remission before relapse was available for 9 out of 10 relapses under tocilizumab and for 13 out of 21 relapses under anti-TNF treatment.
In the reported pediatric patients with TAK, anti-TNF drug use was more frequent than tocilizumab (74.2% versus 36.9%, p < 0.001). No significant difference was observed between the two groups concerning age at diagnosis or sex (p = 0.209 and p = 0.237, respectively). A notable finding was the higher prevalence of hypertension in the anti-TNF drug group than the patients in the tocilizumab group (p = 0.004). However, no significant differences were observed between the two groups regarding other clinical findings, acute phase reactant levels, or radiological findings (p > 0.05 for all).
The concomitant treatments indicated for 198 patients included glucocorticoids and methotrexate in most (84.3% and 41.4%, respectively). Previous treatments indicated for 191 patients similarly included glucocorticoids and methotrexate in most patients (85.3% and 44.5%, respectively). Concurrent administration of glucocorticoids was more frequent during tocilizumab treatment compared with anti-TNF treatment (p = 0.024). The frequency of concomitant and previous conventional DMARD use was not different between the anti-TNF and tocilizumab groups (p = 0.187 and p = 0.255, respectively).
The median (IQR) durations of treatment did not differ significantly between anti-TNF and tocilizumab groups (12 [16.2] versus 12 [14.8] months, respectively; p = 0.966) (Table 1). Improvement was observed during 74 (64.9%) out of 114 treatment courses with anti-TNF drugs, while this proportion was 70.9% (39 out of 55 treatment episodes) with tocilizumab (p = 0.438). The disease duration before biologic treatment or activity status at the start of biologic treatment did not differ significantly between anti-TNF and tocilizumab groups (Table 1). Relapses were observed around 50% of treatment courses in both treatment groups (p = 0.472). Notably, the median duration of remission prior to relapse was also comparable between the tocilizumab and anti-TNF groups (13 versus 12 months, respectively; p = 0.647).
The most frequently utilized anti-TNF drug was infliximab (n = 136, 75.9%), followed by adalimumab (ADA) (n = 27, 15.1%) (Table 2). The improvement frequencies for infliximab and adalimumab were 71.1% (n = 59/83) and 45.5% (n = 10/22), respectively.
Table 2.
Treatment responses, relapse status, and adverse events in patients with pediatric Takayasu arteritis according to type of biologic drugs
| Biologic drug | Number of treatment courses, n | Duration of treatment, months, median (IQR) | Improvementa , n (%) | Relapse, n (%) | Adverse event |
|---|---|---|---|---|---|
| Tocilizumab | 83 | 12 (14.8) | 39/55 (70.9)70.9 | 10/21 (47.6) | 0/8 |
| All anti-TNF drugs | 167 | 12 (16.2) | 74/114 (64.9) | 21/39 (53.8) |
Allergic reaction (n = 2/18) Infusion reaction (n = 1/18) |
| Infliximab | 136 | 12 (24) | 59/83 (71.1) | 17/25 (68) |
Allergic reaction (n = 2/17) Infusion reaction (n = 1/17) |
| Adalimumab | 27 | 22 (13) | 10/22 (45.5) |
3/10 (30) 30 |
NR |
| Etanercept | 6 | 3 (7) | 3/5 (60) | 1/2 (50) | 0/1 |
| Golimumab | 2 | 4, NR | 0/2 (0) | 1/1 (100) | NR |
| Anti-TNF drug type not specified | 8 | NR | NR | NR | NR |
NR, not reported; TNF, tumor necrosis factor
aComplete clinical response, partial clinical response, or any mention of improvement in disease activity were all categorized as “improvement.” Conversely, reports of disease progression or lack of improvement were categorized as “no improvement.”
Among the 25 patients who received both anti-TNF drugs and tocilizumab during the follow-up [20, 21, 25, 30, 34, 36, 38, 39, 48, 59, 61, 64, 68, 70, 73, 89, 97, 103], 14 patients were switched from anti-TNF drugs to tocilizumab and 11 from tocilizumab to anti-TNF drugs due to treatment failure. Among the patients who were switched from anti-TNF drugs to tocilizumab, eight were switched from infliximab, five from adalimumab, and one from etanercept to tocilizumab. Among the patients who were switched from tocilizumab to anti-TNF drugs, five were switched from tocilizumab to infliximab, five were switched to adalimumab, and one was switched to golimumab. Of the patients who were switched from anti-TNF drugs to tocilizumab, 76.9% (n = 10/13) improved with tocilizumab. Improvement was achieved in 81.8% (n = 9/11) of those who switched from tocilizumab to anti-TNF drugs. No statistically significant difference was found regarding effectiveness after switching from one drug to another (p = 0.769).
Data regarding the adverse events were present during 26 treatment courses of anti-TNF drugs (n = 18) or tocilizumab (n = 8) (Table 2). Two patients treated with infliximab experienced an allergic reaction (n = 2/17, 11.8%) [39, 61] and one had an infusion reaction (n = 1/17, 5.9%) [97]. There were no reported adverse events for tocilizumab (n = 8) and for the rest of the anti-TNF treatment courses (n = 15).
There was no case with tuberculosis that was reported to be associated with anti-TNF drug or tocilizumab use among included reports. However, tuberculosis was present in two patients before biologic treatment, and tocilizumab was the biologic of choice in these cases [98, 103].
Long-term outcomes were inconsistently reported across the included studies. Documented organ damage events included heart failure (n = 7), ischemic stroke (n = 2), renal failure (n = 1), and visual loss (n = 1) (Table 1). Vascular surgical interventions were described in 16 cases. Mortality was reported in five patients. There was no significant difference between the two treatment groups with regards to long-term outcome measures.
Discussion
This review represents a very comprehensive analysis of the literature regarding the available data on anti-TNF drug and tocilizumab use in pediatric TAK. Although there are more reports on anti-TNF drug than tocilizumab use, the effectiveness of these biologics was similar. In addition, their safety profile seems to be comparable and acceptable. The scarcity of controlled studies makes it challenging to point at the advantages or disadvantages of these therapies compared with each other.
There is only one randomized, head-to-head comparison study in the literature for anti-TNF drugs and tocilizumab in TAK [108]. In that study, adalimumab (n = 21) was compared with tocilizumab (n = 19), and only adult patients were included. The authors reported a higher efficacy rate at month 6 for adalimumab compared with tocilizumab group (85.71% versus 52.63%, respectively; p = 0.02). Further, efficacy rates at 9 and 12 months, relapse rates, and incidences of adverse events during the first 12 months of treatment were comparable between the two groups (p > 0.05). However, as highlighted in the letter by Misra et al. [109], the patients in the adalimumab group had shorter disease duration and treatment-naïve patients were less frequent in the tocilizumab group. Furthermore, when glucocorticoid dose in the definition of remission was changed to ≤ 10 mg from ≤ 15 mg, there was no longer a significant difference between the two groups. Thus, these factors might have biased the results [109]. It was noteworthy that there were no significant differences regarding relapse rate and adverse event incidence between the two treatment arms [108].
The present study highlights the comparable effectiveness and safety profiles of anti-TNF drugs and tocilizumab in the management of pediatric TAK. Despite the higher frequency of anti-TNF drug use, clinical effectiveness and relapse frequencies were similar between the two groups, indicating that both treatment modalities are viable options. The most commonly used anti-TNF drug, infliximab, demonstrated a higher ratio of improvement than adalimumab, suggesting potential variability in effectiveness among specific agents within the anti-TNF drug class. Among the 25 patients who received both anti-TNF drugs and tocilizumab, there was no evidence to suggest the superiority of one drug over the other.
There were a few differences between the anti-TNF and tocilizumab groups in this review. An interesting observation was the higher concurrent use of glucocorticoids during tocilizumab treatment compared with anti-TNF treatment. This could indicate a tendency for tocilizumab to be used in patients with more severe disease or in cases where additional immunosuppressive treatment is deemed necessary.
The adverse events reported were rare and limited to infliximab, suggesting an acceptable safety profile for both biologic grups. However, adverse events were not addressed in all reports, raising the possibility of reporting bias. In addition, the small sample size and the lack of controlled studies with long-term follow-up make it challenging to draw firm conclusions regarding the safety of these drugs.
There was no report of active tuberculosis under anti-TNF drug or tocilizumab treatment in pediatric TAK, however, tocilizumab was the biologic of choice in two patients with a history of tuberculosis infection [98, 103]. The increased risk of tuberculosis associated with anti-TNF treatment is well recognized. Further, the available evidence suggests that most biologics other than TNF inhibitors are unlikely to pose a significant risk of tuberculosis reactivation [110]. A meta-analysis showed that patients with rheumatoid arthritis receiving anti-TNF treatment had a four times higher tuberculosis incidence compared with those not receiving anti-TNF therapies [111]. Another recent study on adult patients with inflammatory bowel disease has also demonstrated that anti-TNF drugs are associated with a higher risk of active tuberculosis than non-anti-TNF biologic drugs [112].
A higher prevalence of TAK in tuberculosis-endemic regions suggests an association between the two diseases, although the exact nature of this link remains to be elucidated [113]. Tuberculosis infection may play a role in triggering TAK in genetically susceptible individuals [113]. Mycobacterial antigens may stimulate immune responses, leading to the granulomatous inflammation characteristic of TAK [113]. Furthermore, tuberculosis-induced immune activation might exacerbate vascular inflammation, leading to the development of TAK [114]. Thus, patients may have tuberculosis at the time of TAK diagnosis. In these cases, tocilizumab could be more advantageous compared with anti-TNF drugs in the treatment [98, 103].
There are several limitations in this study. The main limitation is that there are no head-to-head comparison studies in pediatric TAK. Moreover, 87% of the data were derived from case reports and case series in this literature review. In addition, the comparability of treatment response was limited by the heterogeneity of the response definition and the patient populations (biologic-naïve or refractory TAK). It was not possible to make a standard definition for remission on the basis of the heterogeneity of the literature data. Having said that, to our knowledge, this is the first literature review that focuses on anti-TNF and anti-IL-6 drug use in pediatric TAK and includes all reported cases in the literature. Although the conclusions are challenged by the above-mentioned limitations; this analysis accurately represents the current available data on this topic.
Conclusions
Although there are more reports on anti-TNF drug use compared with tocilizumab, their efectiveness and safety seem comparable in pediatric TAK. Head-to-head comparison studies with long follow-up would provide invaluable insights guiding the optimum therapeutic decision while managing pediatric patients with TAK.
Supplementary Information
Below is the link to the electronic supplementary material.
Declarations
Funding
Open access funding provided by the Scientific and Technological Research Council of Türkiye (TÜBİTAK).
Conflict of interest
The authors have no conflicts of interest to disclose.
Ethics approval
Not applicable.
Consent to participate
Not applicable.
Consent to publish
Not applicable.
Data availability
The manuscript and online resources present all data related to this systematic review.
Code availability
Not applicable.
Author contributions
Ezgi Deniz Batu had the idea for the article, performed the literature search and data analysis, wrote the first draft of the manuscript, and reviewed and critically revised the manuscript; Sener Sener performed the literature search, data analysis, and reviewed and critically revised the manuscript.
References
- 1.Aeschlimann FA, Barra L, Alsolaimani R, et al. Presentation and disease course of childhood-onset versus adult-onset takayasu arteritis. Arthritis Rheumatol. 2019;71:315–23. [DOI] [PubMed] [Google Scholar]
- 2.Aeschlimann FA, Yeung RSM, Laxer RM. An update on childhood-onset Takayasu arteritis. Front Pediatr. 2022;10: 872313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Onen F, Akkoc N. Epidemiology of Takayasu arteritis. Presse Med. 2017;46:e197–203. [DOI] [PubMed] [Google Scholar]
- 4.Mossberg M, Segelmark M, Kahn R, Englund M, Mohammad A. Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden. Scand J Rheumatol. 2018;47:295–302. [DOI] [PubMed] [Google Scholar]
- 5.Danda D, Goel R, Joseph G, et al. Clinical course of 602 patients with Takayasu’s arteritis: comparison between childhood-onset versus adult onset disease. Rheumatology (Oxford). 2021;60:2246–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Hassold N, Dusser P, Laurent A, et al. Clinical spectrum and outcome of Takayasu’s arteritis in children. Jt Bone Spine. 2024;91: 105735. [DOI] [PubMed] [Google Scholar]
- 7.Arita Y, Ishibashi T, Nakaoka Y. Current immunosuppressive treatment for Takayasu arteritis. Circ J. 2024;88:1605–9. [DOI] [PubMed] [Google Scholar]
- 8.Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021;73:1349–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hellmich B, Agueda A, Monti S, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79:19–30. [DOI] [PubMed] [Google Scholar]
- 10.Members WC, Isselbacher EM, Preventza O, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;80:e223–393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Misra DP, Singh K, Rathore U, et al. The effectiveness of tocilizumab and its comparison with tumor necrosis factor alpha inhibitors for Takayasu Arteritis: a systematic review and meta-analysis. Autoimmun Rev. 2023;22: 103275. [DOI] [PubMed] [Google Scholar]
- 12.Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898. [DOI] [PubMed] [Google Scholar]
- 14.Wells G, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. 2021. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 4 May 2025.
- 15.Moola S, Munn Z, Tufanaru C, et al. Chapter 7: systematic reviews of etiology and risk. In: Aromataris E, Munn Z, editors. JBI manual for evidence synthesis. Joanna Briggs Institute; 2020. pp. 217–69.
- 16.Aeschlimann FA, Eng SWM, Sheikh S, et al. Childhood Takayasu arteritis: disease course and response to therapy. Arthritis Res Ther. 2017;19:255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Aeschlimann FA, Grosse-Wortmann L, Benseler SM, Laxer RM, Hebert D, Yeung RS. Arterial dissection in childhood Takayasu arteritis: not as rare as thought. Pediatr Rheumatol Online J. 2016;14:56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Almasi S, Asadian S, Rezaeian N. Anterior ST-segment elevation myocardial infarction in a teenager: a diagnostic dilemma. JACC Case Rep. 2024;29: 102279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Asano T, Sato S, Temmoku J, et al. Effectiveness of tocilizumab in juvenile patients with refractory Takayasu arteritis: two case reports. Medicine (Baltimore). 2020;99: e18890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Batu ED, Sönmez HE, Hazırolan T, Özaltın F, Bilginer Y, Özen S. Tocilizumab treatment in childhood Takayasu arteritis: case series of four patients and systematic review of the literature. Semin Arthritis Rheum. 2017;46:529–35. [DOI] [PubMed] [Google Scholar]
- 21.Baykal G, Sözeri B. Concurrent pyoderma gangrenosum and Takayasu arteritis in an infant: diagnostic challenges and treatment considerations. Turk J Pediatr. 2024;66:116–23. [DOI] [PubMed] [Google Scholar]
- 22.Bikouli EDC, Vazeou A, Xatzipsalti M, Servos G, Delis D, Maritsi DN. Blau Syndrome complicated by atypical type IIa Takayasu arteritis. J Child Sci. 2021;11:e313–6. [Google Scholar]
- 23.Borhani Haghighi A, Mahmoudi Nezhad GS, Amoozgar H. Lifesaving vertebral artery stenting in a child with Takayasu arteritis. Iran J Pediatr. 2015;25: e262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Bracaglia C, Buonuomo PS, Campana A, Insalaco A, Nicolai R, Cortis E. Early diagnosis of pediatric Takayasu arteritis (TA) not fullfiling the ACR criteria. Clin Exp Rheumatol. 2009;27:S140. [PubMed] [Google Scholar]
- 25.Bravo Mancheño B, Perin F, Guez Vázquez Del Rey Mdel M, García Sánchez A, Alcázar Romero PP. Successful tocilizumab treatment in a child with refractory Takayasu arteritis. Pediatrics. 2012;130:e1720–4. [DOI] [PubMed]
- 26.Buonuomo PS, Bracaglia C, Campana A, et al. Infliximab therapy in pediatric Takayasu’s arteritis: report of two cases. Rheumatol Int. 2011;31:93–5. [DOI] [PubMed] [Google Scholar]
- 27.Çakar N, Özçakar ZB, Soy D, et al. Renal involvement in childhood vasculitis. Nephron Clin Pract. 2008;108:c202–6. [DOI] [PubMed] [Google Scholar]
- 28.Cakar N, Yalcinkaya F, Duzova A, et al. Takayasu arteritis in children. J Rheumatol. 2008;35:913–9. [PubMed] [Google Scholar]
- 29.Cañas CA, Cañas F, Izquierdo JH, et al. Efficacy and safety of anti-interleukin 6 receptor monoclonal antibody (tocilizumab) in Colombian patients with Takayasu arteritis. J Clin Rheumatol. 2014;20:125–9. [DOI] [PubMed] [Google Scholar]
- 30.Choe YJ, Blatt DB, Yalcindag A, Geffert SF, Bobenchik AM, Michelow IC. Cryptococcus albidus fungemia in an immunosuppressed child: case report and systematic literature review. J Pediatr Infect Dis Soc. 2020;9:100–5. [DOI] [PubMed] [Google Scholar]
- 31.Clemente G, Hilário MO, Len C, et al. Brazilian multicenter study of 71 patients with juvenile-onset Takayasu’s arteritis: clinical and angiographic features. Rev Bras Reumatol Engl Ed. 2016;56:145–51. [DOI] [PubMed] [Google Scholar]
- 32.Clemente G, Pereira RMR, Aikawa N, et al. Is positron emission tomography/magnetic resonance imaging a reliable tool for detecting vascular activity in treated childhood-onset Takayasu’s arteritis? A multicentre study. Rheumatology (Oxford). 2022;61:554–62. [DOI] [PubMed] [Google Scholar]
- 33.De Guerra VC, Hashmi H, Kramer B, et al. A case report of Takayasu’s arteritis and ulcerative colitis in a pediatric patient with chronic recurrent multifocal osteomyelitis successfully treated with infliximab: diagnostic clues in disease associations and immune dysregulation. Case Rep Rheumatol. 2019;2019:8157969. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Decker P, Olivier P, Risse J, Zuily S, Wahl D. Tocilizumab and refractory Takayasu disease: four case reports and systematic review. Autoimmun Rev. 2018;17:353–60. [DOI] [PubMed] [Google Scholar]
- 35.Della Rossa A, Tavoni A, Merlini G, et al. Two Takayasu arteritis patients successfully treated with infliximab: a potential disease-modifying agent? Rheumatology (Oxford). 2005;44:1074–5. [DOI] [PubMed] [Google Scholar]
- 36.Desai R, Barr B, Vesely M, Aktay R, Forbess L. STEMI following in-stent restenosis in coronary Takayasu arteritis with pyoderma gangrenosum in a teenaged athlete. JACC Case Rep. 2024;29: 102487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.El-Matary W, Persad R. Takayasu’s aortitis and infliximab. J Pediatr. 2009;155:151. [DOI] [PubMed] [Google Scholar]
- 38.Eleftheriou D, Varnier G, Dolezalova P, McMahon AM, Al-Obaidi M, Brogan PA. Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom. Arthritis Res Ther. 2015;17:36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Fatehi Hassanabad A, Dagher O, Jefferson HL, et al. Delayed dehiscence of modified mechanical Bentall 7 years postsurgery for Takayasu’s arteritis. J Card Surg. 2019;34:352–5. [DOI] [PubMed] [Google Scholar]
- 40.Filocamo G, Buoncompagni A, Viola S, et al. Treatment of Takayasu’s arteritis with tumor necrosis factor antagonists. J Pediatr. 2008;153:432–4. [DOI] [PubMed] [Google Scholar]
- 41.Fuentes Domínguez L, Cervera Bravo Á, Paniagua Correa C. Takayasu's arteritis in an adolescent with fever of unknown origin: the contribution of PET-CT in the diagnosis. BMJ Case Rep. 2022;15. [DOI] [PMC free article] [PubMed]
- 42.Fujita Y, Tomiita M, Saida S, et al. Intravenous tocilizumab for Takayasu arteritis with aortic aneurysms, bilateral renal artery stenosis, and atypical aortic coarctation in a 2-year-old girl. Mod Rheumatol Case Rep. 2023;7:160–5. [DOI] [PubMed] [Google Scholar]
- 43.Ghoshal S, Bronen RA, McCarthy PL, Pels SG, Beslow LA. Acute stroke in a girl with an absent radial pulse. Pediatr Neurol. 2016;62:77–8. [DOI] [PubMed] [Google Scholar]
- 44.Ghosn S, Malek J, Shbaklo Z, Matta M, Uthman I. Takayasu disease presenting as malignant pyoderma gangrenosum in a child with relapsing polychondritis. J Am Acad Dermatol. 2008;59:S84-87. [DOI] [PubMed] [Google Scholar]
- 45.Goel R, Danda D, Kumar S, Joseph G. Rapid control of disease activity by tocilizumab in 10 “difficult-to-treat” cases of Takayasu arteritis. Int J Rheum Dis. 2013;16:754–61. [DOI] [PubMed] [Google Scholar]
- 46.Grotenhuis HB, Aeschlimann FA, Hui W, et al. Increased arterial stiffness adversely affects left ventricular mechanics in patients with pediatric Takayasu arteritis from a Toronto cohort. J Clin Rheumatol. 2019;25:171–5. [DOI] [PubMed] [Google Scholar]
- 47.Halaweish I, Patel H, Si MS. Giant aortic aneurysm in a child with Takayasu arteritis. Cardiol Young. 2016;26:593–5. [DOI] [PubMed] [Google Scholar]
- 48.Hanioka Y, Shimizu K, Yamagami K, et al. Exacerbation of ulcerative colitis with tocilizumab: a report of two cases, one with Takayasu arteritis and the other with relapsing polychondritis. Intern Med. 2021;60:1615–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Harahsheh AS, Kulkarni A, Becker C, Ross RD. Conditions mimicking coarctation of the aorta. Pediatr Cardiol. 2007;28:385–8. [DOI] [PubMed] [Google Scholar]
- 50.Herrera CN, Tomala-Haz JE. Portal hypertension: an uncommon clinical manifestation of Takayasu arteritis in a 9-year-old child. Open Access Rheumatol. 2016;8:115–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Herrmann JL, Ruzmetov M, Rodefeld MD, Hoyer MH, Brown JW. Simultaneous apicoaortic conduit placement and mitral valve replacement in an adolescent with porcelain aorta, aortic stenosis, and mitral stenosis. Ann Thorac Surg. 2009;88:998–1000. [DOI] [PubMed] [Google Scholar]
- 52.Hızal M, Demir S, Polat SE, Özen S, Kiper N. Takayasu arteritis presenting with spontaneous pneumothorax. Turk J Pediatr. 2020;62:879–83. [DOI] [PubMed] [Google Scholar]
- 53.Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004;50:2296–304. [DOI] [PubMed] [Google Scholar]
- 54.Hwang M-S, Hsiao H-J, Wang C-J, Chu J-J, Su W-J, Huang J-L. Takayasu arteritis mimics dilated cardiomyopathy as its initial presentation. Pediatr Neonatol. 2024;65:188–91. [DOI] [PubMed] [Google Scholar]
- 55.Inoue Y, Kawaguchi Y, Shimojo N, et al. A case of infantile Takayasu arteritis with a p.D382E NOD2 mutation: an unusual phenotype of Blau syndrome/early-onset sarcoidosis? Mod Rheumatol. 2013;23:837–9. [DOI] [PubMed]
- 56.Ito S, Tahara N, Hirakata S, et al. Signal intensity of superb micro-vascular imaging associates with the activity of vascular inflammation in Takayasu arteritis. J Nucl Cardiol. 2020;27:1063–5. [DOI] [PubMed] [Google Scholar]
- 57.Iwakura T, Takanashi S, Masuda A, et al. Coronary ostial angioplasty for juvenile Takayasu arteritis involving the coronary artery using external iliac artery grafts. Gen Thorac Cardiovasc Surg. 2022;70:1005–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58.Javadi Parvaneh V, Jari M, Rahmani K, Azma R, Shiari R. Five-day fever: the main presentation of childhood-onset Takayasu arteritis. Clin Case Rep. 2020;8:2361–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59.Jin J, Zhao Y, Gao X, et al. A retrospective study of infantile-onset Takayasu arteritis: experience from a tertiary referral center in China. Front Cardiovasc Med. 2024;11:1249305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Kanamori K, Ogura M, Ishikura K, Ishiguro A, Ito S. Tocilizumab for juvenile Takayasu arteritis complicated with acute heart failure at onset. Mod Rheumatol Case Rep. 2022;6:226–9. [DOI] [PubMed] [Google Scholar]
- 61.Kang M, Lai J, Zhang D, Xu Y, Zhu J, Li M. Clinical observations on infliximab treatment of infantile onset Takayasu arteritis. Pediatr Rheumatol Online J. 2022;20:61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 62.Karageorgaki ZT, Mavragani CP, Papathanasiou MA, Skopouli FN. Infliximab in Takayasu arteritis: a safe alternative? Clin Rheumatol. 2007;26:984–7. [DOI] [PubMed] [Google Scholar]
- 63.Karia VR, Haymon ML, Espinoza LR, Gedalia A. Severe abdominal pain in 2 teenage girls. Clin Pediatr (Phila). 2011;50:467–9. [DOI] [PubMed] [Google Scholar]
- 64.Kishimoto K, Nozaki Y, Sakurai T, Kinoshita K, Funauchi M, Matsumura I. Takayasu's arteritis diagnosed in an adolescent patient with Crohn's disease: management of biologicals. Life (Basel). 2021;11. [DOI] [PMC free article] [PubMed]
- 65.Kişla Eki̇nci̇ RM, Balci S, Pi̇şki̇n FC, Varan C, Erdem S, Yilmaz M. Pre-pulseless Takayasu arteritis in a child represented with prolonged fever of unknown origin and successful management with concomitant mycophenolate mofetil and infliximab. Arch Rheumatol. 2020;35:278–82. [DOI] [PMC free article] [PubMed]
- 66.Lee M, Meidan E, Son M, Dionne A, Newburger JW, Friedman KG. Coronary artery aneurysms in children is not always Kawasaki disease: a case report on Takayasu arteritis. BMC Rheumatol. 2021;5:27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 67.Lei C, Huang Y, Yuan S, et al. Takayasu arteritis with coronary artery involvement: differences between pediatric and adult patients. Can J Cardiol. 2020;36:535–42. [DOI] [PubMed] [Google Scholar]
- 68.Liebling EJ, Peterson R, Victoria T, Burnham JM. Aortic ulceration in a tocilizumab-treated patient with Takayasu arteritis. Ann Rheum Dis. 2019;78: e116. [DOI] [PubMed] [Google Scholar]
- 69.Masri SI, Majdalani MN, Bitar FF. Novel percutaneous femoral arterial-transthoracic approach for closure of ascending aortic pseudoaneurysm with a septal occluder device in a child. Cardiol Young. 2014;24:752–5. [DOI] [PubMed] [Google Scholar]
- 70.Masui S, Yonezawa A, Izawa K, et al. Plasma infliximab monitoring contributes to optimize Takayasu arteritis treatment: a case report. J Pharm Health Care Sci. 2019;5:9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 71.McBrien A, Griselli M, Friswell M, Hasan A, Kirk R. Heart transplantation following myocardial infarction due to Takayasu’s arteritis. Pediatr Transplant. 2012;16:E291-295. [DOI] [PubMed] [Google Scholar]
- 72.Mekik Akar E, Aydın F, Tüzüner A, et al. Renal autotransplantation in a patient with bilateral renal artery stenosis secondary to Takayasu arteritis. Int J Organ Transplant Med. 2020;11:37–41. [PMC free article] [PubMed] [Google Scholar]
- 73.Miller-Barmak A, Sztajnbok F, Balik Z, et al. Infantile Takayasu: clinical features and long-term outcome. Rheumatology (Oxford). 2023;62:3126–32. [DOI] [PubMed] [Google Scholar]
- 74.Mohan S, Poff S, Torok KS. Coronary artery involvement in pediatric Takayasu’s arteritis: case report and literature review. Pediatr Rheumatol Online J. 2013;11:4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 75.Mollet T, Henderson FW, Groben PA, Burkhart CN, Morrell DS. Epidermolysis bullosa nevus-like lesions in a pediatric patient with pyoderma gangrenosum. Pediatr Dermatol. 2011;28:32–4. [DOI] [PubMed] [Google Scholar]
- 76.Morishita KA, Rosendahl K, Brogan PA. Familial Takayasu arteritis—a pediatric case and a review of the literature. Pediatr Rheumatol Online J. 2011;9:6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 77.Mulla I, Yeung RSM, Noone DG, Bell-Peter A, Pagnoux C. Paediatric-to-adult transition experience in vasculitis: report of a model of care and outcomes. Clin Exp Rheumatol. 2022;40:772–8. [DOI] [PubMed] [Google Scholar]
- 78.Nakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2018;77:348–54. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 79.Nascif AK, Lemos MD, Oliveira NS, Perim PC, Cordeiro AC, Quintino M. Takayasu’s arteritis in children and adolescents: report of three cases. Rev Bras Reumatol. 2011;51:527–30. [PubMed] [Google Scholar]
- 80.Osman M, Aaron S, Noga M, Yacyshyn E. Takayasu’s arteritis progression on anti-TNF biologics: a case series. Clin Rheumatol. 2011;30:703–6. [DOI] [PubMed] [Google Scholar]
- 81.Polyakova I, Iannucci G, George R, Gill A, Patel DG, Rouster-Stevens K. Simultaneous presentation of Crohn’s disease and Takayasu arteritis in a teenage patient. J Investig Med High Impact Case Rep. 2020;8:2324709620977317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Quartuccio L, Schiavon F, Zuliani F, et al. Long-term efficacy and improvement of health-related quality of life in patients with Takayasu’s arteritis treated with infliximab. Clin Exp Rheumatol. 2012;30:922–8. [PubMed] [Google Scholar]
- 83.Ratuapli S, Mazlumzadeh M, Gurudu S, Money S, Heigh R. Coexisting Crohn’s disease and Takayasu’s arteritis in two patients treated with anti-TNF-α therapies. Case Rep Gastroenterol. 2010;4:35–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 84.Reid HW, Moorthy G, Clark D, Cannon L, Ming DY. A big headache: an unusual case of hypertensive urgency in an adolescent. Clin Pediatr. 2021;60:427–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85.Sahin S, Hopurcuoglu D, Bektas S, et al. Childhood-onset Takayasu arteritis: a 15-year experience from a tertiary referral center. Int J Rheum Dis. 2019;22:132–9. [DOI] [PubMed] [Google Scholar]
- 86.Sakumura N, Irabu H, Inoue N, Mizuta M, Shimizu M. Clinical usefulness of longitudinal IL-6 monitoring in a patient with Takayasu aortitis receiving tocilizumab. Rheumatology (Oxford). 2020;59:252–4. [DOI] [PubMed] [Google Scholar]
- 87.Sato K, Watabe H, Sato A, Ieda M. Acute myocardial infarction associated with diffuse coronary lesions with Takayasu arteritis in a teenager. JACC Cardiovasc Interv. 2022;15:673–4. [DOI] [PubMed] [Google Scholar]
- 88.Sato S, Matsumoto H, Temmoku J, et al. A case of Takayasu arteritis complicated by refractory ulcerative colitis successfully treated with tofacitinib. Rheumatology (Oxford). 2020;59:1773–5. [DOI] [PubMed] [Google Scholar]
- 89.Sener S, Basaran O, Kaya Akca U, et al. Treatment of childhood-onset Takayasu arteritis: switching between anti-TNF and anti-IL-6 agents. Rheumatology (Oxford). 2022;61:4885–91. [DOI] [PubMed] [Google Scholar]
- 90.Shen C, Zhao S, Wang B, Shen Y, Xiao Y, Xu Z. Childhood-onset Takayasu arteritis presenting as pyoderma gangrenosum-like vasculitic ulceration: three case reports and a literature review. Australas J Dermatol. 2022;63:244–7. [DOI] [PubMed] [Google Scholar]
- 91.Shimizu M, Ueno K, Ishikawa S, Tokuhisa Y, Inoue N, Yachie A. Successful multitarget therapy using mizoribine and tacrolimus for refractory Takayasu arteritis. Rheumatology (Oxford). 2014;53:1530–2. [DOI] [PubMed] [Google Scholar]
- 92.Singh N, Hughes M, Sebire N, Brogan P. Takayasu arteritis in infancy. Rheumatology (United Kingdom). 2013;52:2093–5. [DOI] [PubMed] [Google Scholar]
- 93.Sönmez HE, Demir F, Özdel S, et al. Neuroimaging of children with Takayasu arteritis. J Child Neurol. 2021;36:642–7. [DOI] [PubMed] [Google Scholar]
- 94.Stern S, Clemente G, Reiff A, Ramos MP, Marzan KA, Terreri MT. Treatment of Pediatric Takayasu arteritis with infliximab and cyclophosphamide: experience from an American-Brazilian cohort study. J Clin Rheumatol. 2014;20:183–8. [DOI] [PubMed] [Google Scholar]
- 95.Sugita A, Hashimoto S, Sato R, et al. Takayasu’s arteritis in a girl with steroid-dependent nephrotic syndrome: could rituximab be the culprit? Nephrology (Carlton). 2021;26:693–4. [DOI] [PubMed] [Google Scholar]
- 96.Szugye HS, Zeft AS, Spalding SJ. Takayasu Arteritis in the pediatric population: a contemporary United States-based single center cohort. Pediatr Rheumatol Online J. 2014;12:21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 97.Takeuchi I, Kawai T, Nambu M, et al. X-linked inhibitor of apoptosis protein deficiency complicated with Crohn’s disease-like enterocolitis and Takayasu arteritis: a case report. Clin Immunol. 2020;217: 108495. [DOI] [PubMed] [Google Scholar]
- 98.Tian Y, Chen Y. Stroke in Takayasu arteritis with concomitant tuberculosis: an unusual pediatric case report. BMC Pediatr. 2022;22:50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 99.Uthman IW, Chaaban H. The use of sildenafil in pediatric Takayasu arteritis. Clin Rheumatol. 2006;25:550. [DOI] [PubMed] [Google Scholar]
- 100.Wang Y, Duan Y, Su H, et al. Acute non-ST segment elevation myocardial infarction as the first manifestation of Takayasu arteritis in a 16-year-old female patient: a case report and literature review. J Int Med Res. 2023;51:3000605231178599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101.Wu S-Y, Chen C-H, Cheng C-C, Fan H-C. Takayasu’s arteritis presenting as monocular visual loss. Pediatr Neonatol. 2015;56:435–8. [DOI] [PubMed] [Google Scholar]
- 102.Xu Y, Luo L, Su G, et al. Clinical characteristics and risk factors of coronary artery lesions in chinese pediatric Takayasu arteritis patients: a retrospective study. Pediatr Rheumatol Online J. 2023;21:42. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 103.Xuan W, Wang Z, Lin J, et al. Case report: Aggressive progression of acute heart failure due to juvenile tuberculosis-associated Takayasu arteritis with aortic stenosis and thrombosis. Front Cardiovasc Med. 2023;10:1076118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 104.Yamanishi S, Tanabe Y, Watanabe M, et al. A case of seronegative primary Sjögren’s syndrome complicated by Takayasu arteritis in a Japanese girl. Mod Rheumatol Case Rep. 2023;7:148–53. [DOI] [PubMed] [Google Scholar]
- 105.Zhang F, Dong B, Yang L, et al. Adolescent Takayasu's arteritis with hypertensive intracerebral hemorrhage: a case report and literature review. Front Pediatr. 2024;12. [DOI] [PMC free article] [PubMed]
- 106.Zhao M, Gao TJ, Fu YH, et al. Efficacy of tocilizumab combined with glucocorticoid in the treatment of Takayasu arteritis in infants. Scand J Rheumatol. 2023;52:439–40. [DOI] [PubMed] [Google Scholar]
- 107.Zhao M, Liu Y, Hu Z, et al. Takayasu arteritis coexisting with cutaneous leishmaniasis. J Clin Med. 2023;12. [DOI] [PMC free article] [PubMed]
- 108.Wang J, Kong X, Ma L, et al. Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study. Rheumatology (Oxford). 2024;63:1359–67. [DOI] [PubMed] [Google Scholar]
- 109.Misra DP. Comment on: treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis. Rheumatology (Oxford). 2024;63:e156–7. [DOI] [PubMed] [Google Scholar]
- 110.Sultana A, Migliori GB, D’Ambrosio L, et al. Expert views on screening for tuberculosis infection in patients commencing treatment with a biologic agent. J Bras Pneumol. 2024;50: e20240082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 111.Ai JW, Zhang S, Ruan QL, et al. The risk of tuberculosis in patients with rheumatoid arthritis treated with tumor necrosis factor-α antagonist: a metaanalysis of both randomized controlled trials and registry/cohort studies. J Rheumatol. 2015;42:2229–37. [DOI] [PubMed] [Google Scholar]
- 112.Kim MJ, Kim YJ, Jeong D, et al. Comparative risk of serious infections and tuberculosis in Korean patients with inflammatory bowel disease treated with non-anti-TNF biologics or anti-TNF-α agents: a nationwide population-based cohort study. Ther Adv Gastroenterol. 2024;17:17562848241265012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 113.Jain S, Pondaiah SK. Takayasu’s arteritis: review of epidemiology and etiopathogenesis. Indian J Rheumatol. 2015;10:S22–9. [Google Scholar]
- 114.Espinoza JL, Ai S, Matsumura I. New insights on the pathogenesis of Takayasu arteritis: revisiting the microbial theory. Pathogens. 2018;7:73. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Data Availability Statement
The manuscript and online resources present all data related to this systematic review.