Yücel Burcu Bozkaya, Aydog Ozlem, Nalcacioglu Hulya, Yılmaz Ayşegül
Department of Pediatric Rheumatology, Ondokuz Mayis University Faculty of Medicine, Samsun, Turkey.
Department of Pediatric Nephrology, Ondokuz Mayis University Faculty of Medicine, Samsun, Turkey.
Front Pediatr. 2021 Sep 10;9:710501. doi: 10.3389/fped.2021.710501. eCollection 2021.
Anti-interleukin 1 agents are used successfully in colchicine-resistant or intolerant Familial Mediterranean Fever (FMF) patients. Sixty-five patients with FMF who received canakinumab treatment for at least 6 months due to colchicine resistance or intolerance between 2016 and 2020 in our department were retrospectively analyzed. Canakinumab treatment was given subcutaneously every 4 weeks. After completing monthly canakinumab therapy over 12 months, in patients with complete remission, the dosing interval was extended to every 1.5 months for 6 months, then every 2 months for 6 months, and finally every 3 months for a year. In patients without disease activation, canakinumab treatment was discontinued at the end of 3 years and followed up with colchicine treatment. Patients who had a flare switched to the previous dosing interval. In patients with renal amyloidosis, monthly canakinumab treatment was continued without extending the dose intervals. The mean duration of canakinumab use in our patients was 31.4 ± 10.57 months (6-52 months). The mean age at onset of symptoms was 4.65 ± 3.84 (range, 1-18) years, and the mean age at diagnosis was 5.59 ± 3.9 (range, 4-19) years. Complete remission was achieved in 57 (87.6%) and partial remission in seven (10.7%) patients. One patient was unresponsive to treatment. Canakinumab treatment was discontinued in three patients with complete remission and one patient with drug resistance. Erythrocyte sedimentation rate (ESR) (51.85 ± 15.7 vs. 27.80 ± 13.73 mm/h) and C-reactive protein (CRP) [26 (3-73) vs. 5 (1-48) mg/L] values were compared before and after canakinumab treatment in attack-free periods, a significant decrease was found after canakinumab treatment ( < 0.001, < 0.001, respectively). Bodyweight -scores (respectively -0.80 ± 0.86 vs. -0.49 ± 0.92) were compared, similarly, a statistically significant increase after canakinumab treatment ( < 0.001), but no significant increase in height scores (-1.00 ± 0.88 vs. -0.96 ± 0.94) ( = 0.445) was detected. Four patients had FMF-related renal amyloidosis. The decrease in proteinuria with canakinumab treatment was not statistically significant ( = 0.068). Cervical lymphadenitis developed in one and local reactions in two patients. No severe adverse effects requiring discontinuation of canakinumab treatment were observed. Our study showed that canakinumab treatment was highly effective, well-tolerated in pediatric FMF patients, and controlled extension of the canakinumab dose interval was safe.
抗白细胞介素1药物已成功用于对秋水仙碱耐药或不耐受的家族性地中海热（FMF）患者。对2016年至2020年期间在我们科室因秋水仙碱耐药或不耐受而接受卡那单抗治疗至少6个月的65例FMF患者进行了回顾性分析。卡那单抗每4周皮下注射一次。在完成12个月的每月卡那单抗治疗后，完全缓解的患者，给药间隔延长至每1.5个月一次，持续6个月，然后每2个月一次，持续6个月，最后每3个月一次，持续一年。在无疾病激活的患者中，卡那单抗治疗在3年后停止，并继续接受秋水仙碱治疗。病情复发的患者恢复到之前的给药间隔。对于肾淀粉样变性患者，每月继续使用卡那单抗治疗，不延长给药间隔。我们患者使用卡那单抗的平均持续时间为31.4±10.57个月（6 - 52个月）。症状出现时的平均年龄为4.65±3.84（范围1 - 18）岁，诊断时的平均年龄为5.59±3.9（范围4 - 19）岁。57例（87.6%）患者实现完全缓解，7例（10.7%）患者部分缓解。1例患者对治疗无反应。3例完全缓解患者和1例耐药患者停止了卡那单抗治疗。在无发作期比较卡那单抗治疗前后的红细胞沉降率（ESR）（51.85±15.7 vs. 27.80±13.73 mm/h）和C反应蛋白（CRP）[26（3 - 73）vs. 5（1 - 48）mg/L]值，卡那单抗治疗后发现显著降低（分别为<0.001，<0.001）。比较体重评分（分别为-0.80±0.86 vs. -0.49±0.92），同样，卡那单抗治疗后有统计学显著增加（<0.001），但身高评分无显著增加（-1.00±0.88 vs. -0.96±0.94）（P = 0.445）。4例患者有FMF相关的肾淀粉样变性。卡那单抗治疗后蛋白尿的降低无统计学意义（P = 0.068）。1例患者发生颈部淋巴结炎，2例患者出现局部反应。未观察到需要停止卡那单抗治疗的严重不良反应。我们的研究表明，卡那单抗治疗非常有效，在儿科FMF患者中耐受性良好，并且卡那单抗剂量间隔的控制性延长是安全的。
