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American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846


Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

Thorax ; 76(Suppl 2):A178, 2021.
Article in English | ProQuest Central | ID: covidwho-1505966


BackgroundBlood eosinopaenia was one of the earliest reported findings in hospitalised patients with COVID-19, questioning whether eosinophils could have an anti-viral or deleterious role in the immune response against SARS-CoV2. Benralizumab is an anti-IL5R monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA) and causes the near-complete depletion of blood and tissue eosinophils. As such, it offers the opportunity to explore the impact of eosinopaenia at the time of infection on outcome with COVID-19.MethodPatients started on treatment with benralizumab (up until April 2021) for SEA at our regional asthma centre were contacted by telephone throughout May and June 2021 to establish whether they had experienced a confirmed (PCR-positive) SARS-CoV2 infection since commencing benralizumab. Clinical and demographic characteristics were recorded along with the outcome of infection, including the need for hospitalisation or intensive care admission. Patients requiring hospitalisation were compared to those experiencing mild infections.ResultsData on 268 patients treated with benralizumab was collected with 24/268 (9%) confirming SARS-CoV2 infection with a positive PCR test. Of these 18/24 (75%) experienced mild infections that did not require hospitalisation. Of the 6/24 requiring hospitalisation, the median (IQR) length of stay was 6 (1–8) days. No patients required ICU admission or mechanical ventilation. There was no significant difference in baseline characteristics between hospitalised and non-hospitalised patients. However, it is noteworthy that a higher proportion of hospitalised patients were male (50.0% vs 38.9%) and had a higher mean BMI (32.1 vs 29.5).DiscussionIn the context of drug-induced eosinopaenia with benralizumab, 75% of patients with severe asthma experienced mild COVID-19 disease. This is likely to be an underestimate given that other patients may have experienced an asymptomatic infection or not pursued PCR testing in the context of mild infection. Although caution is needed due to the small sample size, these results do not support a significant role for eosinophils in SARS-CoV2 infection.