MacGinnitie Andrew J, Rachid Rima, Gragg Hana, Little Sara V, Lakin Paul, Cianferoni Antonella, Heimall Jennifer, Makhija Melanie, Robison Rachel, Chinthrajah R Sharon, Lee John, Lebovidge Jennifer, Dominguez Tina, Rooney Courtney, Lewis Megan Ott, Koss Jennifer, Burke-Roberts Elizabeth, Chin Kimberly, Logvinenko Tanya, Pongracic Jacqueline A, Umetsu Dale T, Spergel Jonathan, Nadeau Kari C, Schneider Lynda C
Division of Immunology, Boston Children's Hospital, Boston, Mass.
Clinical Research Center, Boston Children's Hospital, Boston, Mass.
J Allergy Clin Immunol. 2017 Mar;139(3):873-881.e8. doi: 10.1016/j.jaci.2016.08.010. Epub 2016 Sep 5.
Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions.
We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients.
Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily.
The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses.
Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.
花生口服免疫疗法是治疗花生过敏的一种有前景的方法,但反应频繁,且一些患者无法实现脱敏。抗IgE药物奥马珠单抗(商品名Xolair;基因泰克公司,加利福尼亚州南旧金山)可能会使花生剂量增加更快并减少反应。
我们试图评估奥马珠单抗是否有助于高度过敏患者快速实现花生脱敏。
37名受试者被随机分为奥马珠单抗组(n = 29)或安慰剂组(n = 8)。治疗12周后,受试者接受为期1天的快速脱敏,花生蛋白剂量最高达250毫克,随后每周增加剂量,直至2000毫克。然后停用奥马珠单抗,受试者继续服用2000毫克花生蛋白。在停止研究药物12周后,受试者接受4000毫克花生蛋白的开放激发试验。如果耐受,受试者继续每日服用4000毫克花生蛋白。
在初始脱敏日,接受奥马珠单抗治疗的受试者耐受的花生剂量中位数为250毫克,而接受安慰剂治疗的受试者为22.5毫克。随后,随机分配到奥马珠单抗组的29名受试者中有23名(79%)在停用奥马珠单抗6周后耐受2000毫克花生蛋白,而接受安慰剂的8名受试者中有1名(12%)耐受(P < 0.01)。23名接受奥马珠单抗治疗的受试者与1名接受安慰剂治疗的受试者通过了4000毫克食物激发试验。尽管接受奥马珠单抗治疗的受试者接触的花生剂量要高得多,但奥马珠单抗治疗组与安慰剂治疗组的总体反应率并无显著降低(优势比为0.57;P = 0.15)。
奥马珠单抗可使花生过敏受试者在短短8周的花生口服免疫疗法中快速实现脱敏。在大多数受试者中,这种脱敏在停用奥马珠单抗后仍可持续。更多研究将有助于明确哪些患者将从这种方法中获益最大。