Background

Comorbidities are common in asthma and may complicate treatment response.

Objective

To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities.

Methods

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.

Results

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.

Conclusion

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.

Trial Registration

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).

中文翻译：

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奥马珠单抗在哮喘患者中的疗效在哮喘相关和过敏合并症数量方面没有差异

背景

合并症在哮喘中很常见，可能会使治疗反应复杂化。

客观的

研究因哮喘相关和过敏性合并症而导致的中度至重度过敏性哮喘患者对奥马珠单抗的反应。

方法

来自安慰剂对照 008/009 (n = 1071)、EXTRA (n = 848) 和 INNOVATE (n = 419) 以及单组 PROSPERO (n = 801) omalizumab 研究的 12 岁或以上患者被纳入。协方差模型的泊松回归/分析被用来估计调整后的急性加重率和 1 秒用力呼气量 (FEV1) 从基线开始的奥马珠单抗开始后亚组的合并症数量变化 (0, 1 [008/009]; 0, 1, ≥2 [额外和创新]；0, 1, 2, ≥3 [PROSPERO])。自我报告的合并症包括过敏性鼻结膜炎、慢性鼻窦炎、复发性急性鼻窦炎、鼻息肉、特应性和接触性皮炎、荨麻疹、食物过敏、过敏反应、其他过敏症、胃食管反流病、嗜酸性粒细胞性食管炎和嗜酸性粒细胞性多血管炎。

结果

在 EXTRA 和 INNOVATE 研究中，在奥马珠单抗治疗的合并症亚组中，没有观察到安慰剂校正的正常化哮喘急性加重相对率降低的一致模式。在 PROSPERO 中，合并症亚组的研究中恶化率相似（0, 0.68；1, 0.70；2, 0.77；≥3, 0.80）。对于所有合并症亚组，在整个研究中观察到奥马珠单抗与安慰剂的 FEV1 改善。在 008/009、EXTRA 或 INNOVATE 中，合并症亚组的 FEV1 改善没有一致差异。同样，在 PROSPERO 中，第 12 个月时 FEV1 相对于基线的变化未观察到组间差异（0, 0.05 L；1, 0.08 L；2, 0.00 L；≥3, 0.04 L）。95% 的置信区间在所有情况下都基本重叠。

结论

在安慰剂对照/单臂研究的这些分析中，无论合并症负担如何，奥马珠单抗治疗的研究中恶化率和 FEV1 改善都相似。

试用注册

ClinicalTrials.gov 标识符如下：EXTRA，NCT00314574（https://clinicaltrials.gov/ct2/show/NCT00314574）；创新，NCT00046748（https://clinicaltrials.gov/ct2/show/NCT00046748）；和 PROSPERO，NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037)。