Childhood Takayasu arteritis: disease course and response to therapy

Abstract

Background: Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome.

Methods: A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit.

Outcome: disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death.

Analysis: logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens.

Results: Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease (p = 0.02). No additional outcome predictor was identified.

Conclusions: Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity.

Keywords: Biologic therapy; Children; Takayasu arteritis; Vasculitis.

Fig. 1

Frequency of arterial vessel involvement at diagnosis. Frequencies (%) of patients with any lesion (stenosis, narrowing, aneurysm, dilatation, dissection, vessel wall thickening and post-contrast enhancement) in the indicated vessel. Frequencies of paired vessels (right/left) are presented as one combined value

Fig. 2

Induction and maintenance treatment regimens in children with childhood TAK presenting with active disease (N = 22). Colored lines depict different therapeutic agents. The patients are grouped according to their induction phase therapy: 1. corticosteroids (grey) only, 2. corticosteroids in combination with methotrexate (light blue), 3. corticosteroids in combination with cyclophosphamide (dark blue) and 4. corticosteroids in combination with biologic agents (red) and methotrexate. The timeline is drawn to scale up to 24 months; additional time of treatment is shown in months between break lines. Also depicted are clinical events, including disease flare, death, tuberculosis infection at diagnosis and disease activity (active/inactive) at last follow-up

Fig. 3

Measures of disease activity and damage in the 22 childhood TAK patients with active disease at diagnosis. The squares represent individual patients. AZA azathioprine, CS corticosteroids, Cyclo cyclophosphamide, FU follow-up, IFX infliximab, ITAS2010 Indian Takayasu Arteritis Activity Score, MMF mycophenolate mofetil, MTX methotrexate, PVAS Pediatric Vasculitis Activity Score, PVDI Pediatric Vasculitis Damage Index, TCZ tocilizumab. *One child was started on cyclophosphamide treatment at 6 weeks and died at time of flare at 4 months after diagnosis. **One child was started on cyclophosphamide treatment 6 weeks after diagnosis. ***One child died 12 days after diagnosis

Fig. 4

Flare-free survival in the 22 childhood TAK patients with active disease at diagnosis. a Flare-free survival separated into different treatment groups (biologics N = 12; cyclophosphamide N = 10; corticosteroids only N = 4; methotrexate/azathioprine/mycophenolate mofetil/leflunomide N = 30 treatment episodes), adjusted for the number of treatment episodes. b Flare-free survival grouped into biologic therapy (N = 12 treatment episodes) and non-biologic therapy (methotrexate, azathioprine, mycophenolate mofetil, leflunomide, corticosteroids, cyclophosphamide, N = 44 treatment episodes), adjusted for the number of treatment episodes