Reduced Long-term Cumulative OCS Exposure for Benralizumab-Treated Patients with Severe Asthma

Introduction: Cumulative systemic corticosteroid exposure is associated with adverse health-related outcomes [1]. In the 28-week ZONDA trial of patients with severe asthma, benralizumab treatment resulted in a 75% reduction from baseline in maintenance oral corticosteroid (OCS) dosage, compared with 25% for placebo [2]. We examined the impact this OCS dosage reduction might have on OCS exposure over 1.5 years for patients with severe asthma.

Methods: OCS maintenance dosage data were collected for patients treated with benralizumab 30 mg (every 8 weeks; first three doses every 4 weeks) in ZONDA (baseline, n = 73; Week 28, n = 68) and followed for up to another 52 weeks (Week 40, n = 64; Week 52, n = 58; Week 80, n = 30). For patients with incomplete data, OCS exposure was projected based on last recorded dosage. Exposure from rescue OCS use was not included in this analysis. We compared estimated median cumulative OCS exposure over 1.5 years for benralizumab-treated patients with estimated exposure if those patients had remained on their ZONDA baseline OCS dosages. In ZONDA, only patients receiving baseline OCS ≤ 12.5 mg/day could eliminate OCS use. Therefore, we also estimated median cumulative OCS exposure for patients with baseline OCS ≤ 12.5 and > 12.5 mg/day.

Results: Median cumulative OCS exposure was estimated at 2.976 g for patients receiving benralizumab and 5.740 g if those patients had remained on their baseline OCS dosages, leading to an estimated median cumulative OCS exposure reduction of 2.764 g over 1.5 years ([Fig. 1]). For patients receiving baseline OCS ≤ 12.5 and > 12.5 mg/day, the median cumulative OCS exposure associated with benralizumab at 1.5 years was 0.865 g and 5.114 g, respectively, with a corresponding reduction compared with remaining on baseline OCS dosages of 4.740 g and 6.116 g, respectively.

Fig. 1 Median cumulative OCS exposure over 1.5 years for Benralizumab-treated patients compared with patients continuing on study-entry OCS dosages.

Conclusions: Benralizumab treatment enables patients with severe asthma to reduce long-term OCS exposure. Cumulative systemic corticosteroid dose-response for most treatment-associated adverse outcomes is reported to begin at cumulative exposures of 1.0 – < 2.5 g.¹ Therefore, the estimated cumulative OCS exposure reduction achieved with benralizumab is likely to result in significant reduction in adverse outcome risk for patients.

• Literature

• 1 J Asthma Allergy 2018; 11: 193-204
• 2 NEJM 2017; 376: 2448-2458