Ugurlu Serdal, Hacioglu Aysa, Adibnia Yasaman, Hamuryudan Vedat, Ozdogan Huri
Division of Rheumatology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey.
Orphanet J Rare Dis. 2017 May 30;12(1):105. doi: 10.1186/s13023-017-0642-0.
There is no established treatment of AA amyloidosis, a long-term complication of various chronic inflammatory diseases associated with increased mortality, such as familial Mediterranian fever (FMF). Recently there are few reports pointing out that tocilizumab(TCZ), an anti IL-6 agent may be effective in AA amyloidosis resistant to conventional treatments. We report our data on the effect of TCZ in patients with FMF complicated with AA amyloidosis.
FMF patients with histologically proven AA amyloidosis, treated with TCZ (8 mg/kg per month) were followed monthly and the changes in creatinine, creatinine clearance, the amount of 24-hour urinary protein, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were noted throughout the treatment period. Adverse effects of the treatment were closely monitored.
TCZ was given to 12 patients (6 F, 6 M) who also continued to receive colchicine (1.9 ± 0.4 mg/day). Coexisting diseases were ankylosing spondylitis(4) and Crohn's disease(1). The mean age was 35.2 ± 10.0 years and the mean follow-up on TCZ was 17.5 ± 14.7 months. The renal functions remained stable (mean creatinine from 1.1 ± 0.9 mg/dl to 1.0 ± 0.6 mg/dl), while a significant decrease in acute phase response (the mean CRP from 18.1 ± 19.5 mg/L to 5.8 ± 7.1 mg/L and ESR from 48.7 ± 31.0 mm/h to 28.7 ± 28.3 mm/h) was observed and the mean 24-hour urinary protein excretion reduced from 6537.6 ± 6526.0 mg/dl to 4745.5 ± 5462.7 mg/dl. Two patients whose renal functions were impaired prior to TCZ therapy improved significantly on this regimen. No infusion reaction was observed. None of the patients experienced any FMF attack under TCZ treatment with the exception of 2, one of whom had less frequent attacks while the other had episodes of erysipelas-like erythema. CONCLUSıON: Tocilizumab improved the acute phase response and the renal function in this group of patients and was generally well tolerated. Besides improving the renal function TCZ seemed to control the recurrence of FMF attacks too. Further studies are warrented to test the efficacy and safety of TCZ in AA amyloidosis secondary to FMF as well as other inflammatory conditions.
AA 淀粉样变性病尚无既定的治疗方法，它是多种慢性炎症性疾病的一种长期并发症，与死亡率增加相关，如家族性地中海热（FMF）。最近有少数报告指出，抗白细胞介素 -6 药物托珠单抗（TCZ）可能对常规治疗耐药的 AA 淀粉样变性病有效。我们报告了关于 TCZ 对 FMF 合并 AA 淀粉样变性病患者疗效的数据。
对经组织学证实为 AA 淀粉样变性病且接受 TCZ（每月 8mg/kg）治疗的 FMF 患者每月进行随访，并记录整个治疗期间肌酐、肌酐清除率、24 小时尿蛋白量、红细胞沉降率（ESR）和 C 反应蛋白（CRP）的变化。密切监测治疗的不良反应。
12 例患者（6 例女性，6 例男性）接受了 TCZ 治疗，他们同时继续接受秋水仙碱（1.9±0.4mg/天）治疗。并存疾病有强直性脊柱炎（4 例）和克罗恩病（1 例）。平均年龄为 35.2±10.0 岁，TCZ 治疗的平均随访时间为 17.5±14.7 个月。肾功能保持稳定（平均肌酐从 1.1±0.9mg/dl 降至 1.0±0.6mg/dl），同时观察到急性期反应显著降低（平均 CRP 从 18.1±19.5mg/L 降至 5.8±7.1mg/L，ESR 从 48.7±31.0mm/h 降至 28.7±28.3mm/h），24 小时尿蛋白排泄平均从 6537.6±6526.0mg/dl 降至 4745.5±5462.7mg/dl。2 例在 TCZ 治疗前肾功能受损的患者在该治疗方案下有显著改善。未观察到输液反应。除 2 例患者外，所有患者在 TCZ 治疗期间均未发生 FMF 发作，其中 1 例发作频率降低，另 1 例出现丹毒样红斑发作。结论：托珠单抗改善了该组患者的急性期反应和肾功能，且总体耐受性良好。除改善肾功能外，TCZ 似乎也能控制 FMF 发作的复发。需要进一步研究来测试 TCZ 在 FMF 继发的 AA 淀粉样变性病以及其他炎症性疾病中的疗效和安全性。
