Adelroth E, Rak S, Haahtela T, Aasand G, Rosenhall L, Zetterstrom O, Byrne A, Champain K, Thirlwell J, Cioppa G D, Sandström T
Department of Respiratory Medicine and Allergy, University Hospital, Umea, Sweden.
J Allergy Clin Immunol. 2000 Aug;106(2):253-9. doi: 10.1067/mai.2000.108310.
Allergic rhinitis is a common condition often requiring treatment.
We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL.
We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL).
Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected.
Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.
过敏性鼻炎是一种常见疾病,常需进行治疗。
我们评估了重组人源化单克隆抗体E25(rhu mAb-E25),一种与循环IgE结合的鼠源抗体的重组人源化构建体,按照预计可将血清游离IgE水平降低至25 ng/mL以下的剂量方案皮下给药时,是否能够控制症状并减少季节性变应性鼻炎(SAR)中伴随药物的摄入量,该疾病由桦树花粉诱发。
我们将251名有SAR病史且对桦树花粉皮肤试验呈阳性反应的成年受试者随机分组,根据基线IgE水平,在季节期间接受2次或3次300 mg的rhu mAb-E25或安慰剂治疗。主要疗效变量是根据双盲治疗期收集的日记数据得出的受试者每日平均鼻部症状严重程度评分(打喷嚏、瘙痒、流涕和鼻塞)。次要疗效变量包括每日急救抗组胺药片的平均数量、使用任何SAR药物的天数比例以及变应性鼻结膜炎特异性生活质量(QOL)。
在每日平均鼻部症状严重程度评分、每日急救抗组胺药片的平均数量、使用任何SAR药物的天数比例以及QOL的所有领域中,观察到了有利于rhu mAb-E25的显著组间差异。rhu mAb-E25治疗的受试者血清游离IgE水平显著更低,且与临床疗效相关。重组人源化单克隆抗体E25耐受性良好。未检测到抗rhu mAb-E25抗体。
与安慰剂相比,rhu mAb-E25在控制桦树花粉诱发的SAR症状方面安全有效,伴随药物使用更少且QOL得到改善。本研究显示了抗IgE抗体在SAR中的治疗潜力。