Biester Sabine, Deuter Christoph, Michels Hartmut, Haefner Renate, Kuemmerle-Deschner Jasmin, Doycheva Deshka, Zierhut Manfred
Department of Ophthalmology, University of Tuebingen, Tuebingen, Germany.
Br J Ophthalmol. 2007 Mar;91(3):319-24. doi: 10.1136/bjo.2006.103721. Epub 2006 Oct 11.
Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not respond sufficiently and there is a high risk of them becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (Humira), a complete humanised anti-TNF alpha antibody.
We retrospectively analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, one was without detectable underlying disease. The age at onset of arthritis varied from 0.5-15 years and for uveitis from 2-19 years. Patients were included when the previous anti-inflammatory therapy had been ineffective. It consisted of systemic steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n = 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n = 3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a) effective: no relapse or more than two relapses less than before treatment, (b) mild: one relapse less than before treatment, (c) no response: no change in relapse rate and (d) worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings), using three out of six parameters of the ACR PED Criteria, was: effective, mild, no response, worsening.
For arthritis (n = 16) the response to Adalimumab was effective in 10 of 16 patients, mild in three patients, three did not respond. For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in one child. Additional immunosuppressive treatment was used in seven of the effectively treated children. Due to elevation of liver enzymes in one patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported.
For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, were not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear.
儿童慢性前葡萄膜炎通常病情严重。尽管使用了各种免疫抑制药物，但一些儿童反应不佳，且有严重致残的高风险。我们团队及其他研究表明，抗TNFα疗法大多无效（依那西普）或部分有效（英夫利昔单抗），且存在过敏反应风险。在此，我们报告18例接受阿达木单抗（修美乐）治疗的年轻患者，阿达木单抗是一种完全人源化的抗TNFα抗体。
我们回顾性分析了18例接受阿达木单抗治疗的患者（20 - 40毫克，每2周一次，无效时每周一次）；17例患有幼年特发性关节炎，1例未检测到潜在疾病。关节炎发病年龄为0.5 - 15岁，葡萄膜炎发病年龄为2 - 19岁。当先前的抗炎治疗无效时纳入患者。先前的治疗包括全身用类固醇（18例）、环孢素A（18例）、甲氨蝶呤（18例）、硫唑嘌呤（12例）、霉酚酸酯（4例）、环磷酰胺（2例）、来氟米特（3例）、依那西普（8例）和英夫利昔单抗（5例）。葡萄膜炎的分级为：（a）有效：无复发或复发次数比治疗前减少超过两次；（b）轻度：复发次数比治疗前减少一次；（c）无反应：复发率无变化；（d）恶化：治疗期间复发次数比治疗前更多。根据美国风湿病学会儿科标准的六个参数中的三个，对关节炎（根据临床发现）的分级为：有效、轻度、无反应、恶化。
对于关节炎（16例），16例患者中有10例对阿达木单抗反应有效，3例为轻度，3例无反应。对于葡萄膜炎（18例），阿达木单抗对16例有效，1例儿童为轻度，1例患者无任何效果。最初反应非常好后，有1例儿童需要缩短用药时间以维持良好的抗炎效果。7例有效治疗的儿童使用了额外的免疫抑制治疗。由于1例同时服用甲氨蝶呤的患者肝酶升高，不得不停用阿达木单抗。自开始阿达木单抗治疗以来，未报告过敏反应或感染频率增加。
对于我们这组患有长期疾病的儿童，我们的结果表明，阿达木单抗对81%的关节炎有效或轻度有效，但对88%的葡萄膜炎有效。虽然这些关于关节炎的结果与其他TNFα阻断药物（依那西普）相当，但阿达木单抗对葡萄膜炎的效果似乎比依那西普好得多。我们团队先前在英夫利昔单抗治疗后发现的过敏反应，在阿达木单抗治疗中未出现。必要的剂量和治疗周期可能需要为每个患者单独确定，目前仍不清楚。
