On-demand anakinra treatment is effective in mevalonate kinase deficiency
On-demand anakinra treatment is effective in mevalonate kinase deficiency
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DOI：
10.1136/ard.2011.149922
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发表时间：
2011-12-01
影响因子：
27.4
通讯作者：
Frenkel, J.
中科院分区：
文献类型：
--
作者：
Bodar, E. J.;Kuijk, L. M.;Frenkel, J.
甲羟戊酸激酶缺乏症（MKD）是一种遗传性自身炎症综合征，以反复发作的发热和炎症为特征。严重的酶缺乏导致甲羟戊酸尿症（MA）和轻度缺乏导致高免疫球蛋白D综合征（HIDS）。治疗仍然是一个挑战。目的观察重组白介素-1受体拮抗剂阿那金对MKD患者的治疗效果。方法采用前瞻性观察性研究。2名MA患者开始连续使用阿那白拉治疗（1-2 mg/kg/天），9名HIDS患者选择连续治疗和按需治疗（从首次发作症状开始，100mg /天或1mg /kg/天，持续5-7天）。结果Anakinra在1例MA患者中诱导部分缓解，而在另1例MA患者中无反应。在一名HIDS患者中，连续治疗7个月后完全缓解，但由于副作用而停止治疗。8名艾滋病患者从一开始就倾向于按需治疗。在12次治疗的发作中，有8次出现临床反应（>=持续时间减少50%），而发作频率没有改变。阿那白在不抑制抗体诱导的情况下预防疫苗接种引起的发热发作。没有发现明显的副作用。结论阿那白拉按需治疗HIDS可减少发热发作的持续时间和严重程度。由于每日注射的负担和相对较长的无症状间隔，所有HIDS患者都倾向于按需治疗。
Background Mevalonate kinase deficiency (MKD) is a hereditary autoinflammatory syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme deficiency results in mevalonic aciduria (MA) and milder deficiency in hyperimmunoglobulin D syndrome (HIDS). Treatment remains a challenge.Objective To observe the effect of the recombinant interleukin-1 receptor antagonist anakinra in patients with MKD.Methods A prospective observational study was undertaken. Two patients with MA started continuous treatment with anakinra (1-2 mg/kg/day) and nine patients with HIDS chose between continuous treatment and on-demand treatment (starting at first symptoms of attack, 100 mg/day or 1 mg/kg/day for 5-7 days).Results Anakinra induced partial remission in one patient with MA but there was no response in the other patient with MA. In one patient with HIDS continuous treatment induced complete remission for 7 months but was stopped because of side effects. Eight patients with HIDS preferred on-demand treatment from the start. This induced a clinical response (>= 50% reduction in duration) in 8 of 12 treated attacks without a change in attack frequency. Anakinra prevented fever attacks due to vaccination without inhibiting antibody induction. No major side effects were seen.Conclusions On-demand treatment with anakinra in HIDS decreases the duration and severity of fever attacks. Because of the burden of daily injections and relatively long asymptomatic intervals of HIDS, all patients with HIDS preferred on-demand treatment.