RECOMBINANT INTERFERON GAMMA-THERAPY FOR ATOPIC-DERMATITIS
RECOMBINANT INTERFERON GAMMA-THERAPY FOR ATOPIC-DERMATITIS
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DOI：
10.1016/0190-9622(93)70026-p
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发表时间：
1993-02-01
影响因子：
13.8
通讯作者：
COOPER, KD
中科院分区：
文献类型：
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作者：
HANIFIN, JM;SCHNEIDER, LC;COOPER, KD
背景：特应性皮炎的特征是免疫异常，包括干扰素γ产生减少的证据。特应性皮炎的治疗选择有限且不能令人满意。先前的公开试验表明重组干扰素-γ（rIFN-γ）在治疗严重特应性皮炎方面具有疗效。我们描述了rIFN-γ治疗的结果，评估了83名中重度特应性皮炎患者的临床、免疫学和实验室安全参数。目的：我们的目的是在一项随机、安慰剂对照、双盲多中心研究中确定重组人干扰素γ治疗对特应性皮炎患者的效果。方法：患者接受50μg/m2 rIFN-γ（n = 40）或安慰剂（n = 43) 每日皮下注射，持续 12 周。 78名患者完成了治疗过程；两名接受 rIFN-gamma 的患者（一名是因为全身副作用）和三名接受安慰剂的患者在完成前停止了治疗。在整个试验过程中对医生和患者的总体反应评估、临床严重程度评分、体表面积参与情况和实验室参数进行监测。 结果：两个治疗组的患者相似，只是 rIFN-gamma 组年龄较大且病程较长。 45% 的 rIFN-gamma 治疗患者和 21% 的安慰剂治疗患者在医生的总体反应评估中取得了超过 50% 的改善 (p = 0.016)。据患者估计，与安慰剂组相比，rIFN-gamma 组的反应也显示出显着改善（53% vs 21%，p = 0.002）。 rIFN-γ治疗的患者红斑（p = 0.035）和抓痕或糜烂（p = 0.045）显着减少。 rIFN-gamma 组的其他特应性症状如结膜炎 (p < 0.002) 也有所减轻。接受 rIFN-γ 治疗的患者中有 30% 至 60% 偶尔会出现头痛、肌痛或寒战，但通过预处理对乙酰氨基酚和睡前给药可以有效预防。五名 rIFN-γ 患者出现 II 级粒细胞减少症，但通过继续治疗恢复正常。 rIFN-γ 组的 6 名患者和安慰剂组的 2 名患者需要减少隔日给药。七名患者的肝转氨酶水平轻度升高，但不影响治疗。平均嗜酸性粒细胞计数显着减少（p = 0.003），而积极治疗组血清 IgE 水平没有显着增加。结论：这项研究表明，在 12 周内每天皮下注射 rIFN-gamma 是安全的、被广泛接受的，并且可以有效减少严重特应性皮炎的炎症、临床症状和嗜酸性粒细胞增多。
Background: Atopic dermatitis is characterized by immunologic abnormalities including evidence for reduced interferon gamma production. Therapeutic options for treatment of atopic dermatitis are limited and unsatisfactory. Previous open trials have suggested efficacy for recombinant interferon-gamma (rIFN-gamma) in treatment of severe atopic dermatitis. We describe the results of treatment with rIFN-gamma, assessing clinical, immunologic, and laboratory safety parameters in 83 patients with moderate to severe atopic dermatitis.Objective: Our purpose was to determine in a randomized, placebo-controlled, double-blind multicenter study the effects of recombinant human interferon gamma therapy in patients with atopic dermatitis.Methods: Patients received 50 mug/m2 rIFN-gamma (n = 40) or placebo (n = 43) by daily subcutaneous injection for 12 weeks. Seventy-eight patients completed the treatment course; two patients receiving rIFN-gamma (one because of constitutional side effects) and three receiving placebo discontinued treatment before completion. Physician and patient overall response evaluations, clinical severity scores, body surface area involvement, and laboratory parameters were monitored throughout the trial.Results: Patients in both treatment groups were similar except that the rIFN-gamma group was older and had a longer disease duration. Forty-five percent of rIFN-gamma-treated patients and 21% of placebo-treated patients achieved greater than 50% improvement in physicians' overall response evaluations (p = 0.016). As estimated by patients, responses also showed significant improvement in the rIFN-gamma group compared with the placebo group (53% vs 21%, p = 0.002). Significant reductions in erythema (p = 0.035) and in excoriations or erosions (p = 0.045) occurred in rIFN-gamma-treated patients. Other atopic symptoms such as conjunctivitis (p < 0.002) were also reduced in the rIFN-gamma group. Occasional headaches, myalgias, or chills occurred in 30% to 60% of rIFN-gamma-treated patients but were effectively prevented by pretreatment acetaminophen and by dosing at bedtime. Grade II granulocytopenia occurred in five rIFN-gamma patients but normalized with continued treatment. Reduction to alternate-day dosing was necessary for six patients in the rIFN-gamma group and two in the placebo group. Seven had mild elevations of hepatic transaminase levels that did not affect therapy. The mean eosinophil count was significantly reduced (p = 0.003), whereas a nonsignificant increase in serum IgE levels occurred in the active treatment group.Conclusion: This study demonstrated that rIFN-gamma given by daily subcutaneous injection over a 12-week period was safe, well accepted, and effective in reducing inflammation, clinical symptoms, and eosinophilia in severe atopic dermatitis.