Background Takayasu arteritis (TAK) is a rare disease that mostly affects young females and causes inflammation, stenosis and dilatation of the aorta and its main branches. Although glucocorticoids are effective, relapses occur frequently [1]. Recently, the efficacy of biologics has been reported in refractory TAK. HLA-B*52 is a major genetic risk factor and associated with the severity [2]. Our group reported a SNP in the regions of IL12B gene associated with the onset of TAK, and the patients with risk alleles at the SNP showed significantly severer symptoms [3].

Objectives To evaluate the efficacy and safety of biologics in the treatment of refractory TAK, we analyzed the clinical profiles and genetic information of patients treated with biologics in our institute.

Methods We searched for TAK patients who used biologics in 163 TAK cases treated in Kyoto University Hospital from 2000 to 2016. From medical records, we extracted information of classifications, symptoms, complications, ESR, CRP, dose of prednisolone (PSL), use of immunosuppressive agents (IS), and adverse events at 0, 1, 6 12 months after the initiation of biologics.

Results Of 163 cases, 12 (7.4%) were treated with biologics. Two were excluded because biologics were used for coexisting rheumatoid arthritis. Remaining 10 cases were treated with infliximab (IFX, 3–5 mg/kg div. bimonthly, N=4), tocilizumab (TCZ, 8 mg/kg div. monthly, N=3) or ustekinumab (UST, 45 mg s.c. trimonthly, N=3). Sex ratio was 1:9. The age of onset was 29.4±12.2 y.o. (mean±S.D.). According to Hata's classification [4], they were categorized into types I (N=3), IIa (2) and V (5). Three patients had aortic regurgitation. The number of IS used in the past was 1.7±0.8 per patient. B*52 was positive in 7 (70%) patients. All the cases had risk-type alleles (A vs. C) of IL12B SNP (AA: AC: CC =4: 6: 0). ESR was significantly decreased (p=0.009) and CRP showed a tendency to decrease after 12 mo. (Table 1). Dose of PSL was significantly decreased from 10.6±1.9 to 7.7±2.4 mg/day after 12 mo. (p=0.018). We could not find significant improvements in imaging modalities such as MR and ultrasonography. Overall duration of treatments with biologics was 39±22 months. Two cases discontinued IFX due to occurrence of breast cancer and infusion reaction, respectively. Chronic heart failure was exacerbated in a case treated with TCZ. Two of 3 patients treated with UST exhibited steroid- sparing effects and none of them discontinued UST in the mean observation period of 31 mo.

Conclusions Biologics showed steroid-sparing effects in refractory TAK. Besides, there was a tendency that patients who used biologics had B*52 and the risk-type allele of IL12B SNP, implicating the refractory courses of them.

References

1. Maksimowicz-McKinnon K, Clin Exp Rheumatol 25:S58–9, 2007.

2. Numano F, Jpn Circ J 46(2):184–9, 1982.

3. Terao C, Am J Hum Genet 93(2):289–97, 2013.

4. Hata A, Int J Cardiol 54 Suppl:S155–163, 1996.

References

Disclosure of Interest None declared