Southwest Asthma and Allergy Associates, Houston, Texas.
University of California San Francisco, San Francisco, California.
Ann Allergy Asthma Immunol. 2021 Jun;126(6):666-673. doi: 10.1016/j.anai.2021.01.015. Epub 2021 Jan 17.
Comorbidities are common in asthma and may complicate treatment response.
To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities.
Patients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis.
In the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances.
In these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden.
ClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).
哮喘常伴有合并症，可能使治疗反应复杂化。
通过与哮喘相关的合并症和过敏性合并症来研究奥马珠单抗治疗中重度过敏性哮喘患者的反应。
纳入了安慰剂对照 008/009（n=1071）、EXTRA（n=848）和 INNOVATE（n=419）以及单臂 PROSPERO（n=801）奥马珠单抗研究中的年龄在 12 岁及以上的患者。使用泊松回归/协方差分析模型，根据合并症的数量（0、1[008/009]；0、1、≥2[EXTRA 和 INNOVATE]；0、1、2、≥3[PROSPERO]），估算起始奥马珠单抗治疗后校正的哮喘加重率和用力呼气量第一秒（FEV1）的变化。自报的合并症包括过敏性鼻结膜炎、慢性鼻-鼻窦炎、复发性急性鼻窦炎、鼻息肉、特应性皮炎和接触性皮炎、荨麻疹、食物过敏、过敏反应、其他过敏、胃食管反流病、嗜酸性食管炎和嗜酸性粒细胞性肉芽肿性多血管炎。
在 EXTRA 和 INNOVATE 研究中，奥马珠单抗治疗的各合并症亚组之间，校正后的哮喘加重率相对降低无一致模式。在 PROSPERO 中，各合并症亚组的研究期间加重率相似（0、0.68；1、0.70；2、0.77；≥3、0.80）。与安慰剂相比，奥马珠单抗治疗在整个研究过程中均可改善 FEV1。在 008/009、EXTRA 或 INNOVATE 中，各合并症亚组的 FEV1 改善情况之间无一致差异。同样，在 PROSPERO 中，在第 12 个月时，各亚组间的 FEV1 自基线的变化也无差异（0、0.05 L；1、0.08 L；2、0.00 L；≥3、0.04 L）。在所有情况下，95%置信区间均有很大重叠。
在这些安慰剂对照/单臂研究的分析中，奥马珠单抗治疗的研究期间加重率和 FEV1 改善情况相似，与合并症负担无关。
临床试验.gov 标识符如下：EXTRA，NCT00314574（https://clinicaltrials.gov/ct2/show/NCT00314574）；INNOVATE，NCT00046748（https://clinicaltrials.gov/ct2/show/NCT00046748）；和 PROSPERO，NCT01922037（https://clinicaltrials.gov/ct2/show/NCT01922037）。
