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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 1):A144-A145, 2021.
Article in English | EMBASE | ID: covidwho-1146446


Introduction: Mepolizumab is a biologic agent targeting interleukin (IL)-5 which is currently licensed as add-on therapy for severe eosinophilic asthmatic (SEA). It is usually administered in a hospital setting but with the option of homecare being introduced in 2019, the 4-weekly subcutaneous injections can be self-administered at home. We investigated whether there was a change in asthma control following the transition to home administration and whether a differential response to treatment exists following transition to homecare before and after the onset of the COVID-19 pandemic. Methods: Patients receiving mepolizumab via home care were stratified according to those who had a planned transition to homecare prior to 1st Feb 2020 versus those who had an unplanned transition after this date necessitated by the COVID-19 pandemic. The last Asthma Control Questionnaire-6 (ACQ6) measured in clinic ('baseline') was compared with that collected by telephone consultation 6-8 weeks after transition ('homecare'). Patients were excluded if both values were not available. Results: Of 87 mepolizumab patients included in the analysis, 46 were planned transitions. There was no significant (Figure presented) difference in the pre-biologic ACQ6 (p=0.07) between groups. Immediately prior to transition to homecare (baseline), the planned group had a lower mean ACQ6 than those in the unplanned group (1.19 vs 1.90, P=0.004). The ACQ6 on homecare decreased significantly in both groups (-0.47 in the planned group vs -0.56 in the unplanned group, both P<0.001). The ACQ6 for the planned cohort during homecare was significantly lower than that for the unplanned group (0.72 vs 1.34, P=0.012) (figure 1). (Table presented) Conclusions: We found a significant improvement in ACQ6 for all SEA patients established on Mepolizumab who transitioned to home mepolizumab administration. This improvement occurred irrespective of whether the transition was 'planned' or 'unplanned'. Further research is required to understand the potential influence of shielding during lockdown and the method of ACQ assessment (telephone vs face-to-face ACQ reporting in clinic) on this improvement.

Thorax ; 76(SUPPL 1):A144, 2021.
Article in English | EMBASE | ID: covidwho-1146445


Introduction: The COVID-19 pandemic necessitated the rapid transition of large numbers of patients onto homecare to facilitate on-going therapy in a cohort of patients who were 'shielding'. Alongside this, patients continued to need to be initiated on biologic therapy in spite of the pandemic. The impact of administering biologic therapy at home is largely unknown, yet crucial to optimise patient outcome and minimise steroid burden. We investigated whether there was a differential response following transition to homecare of established patients versus those newly started. Methods: Patients with severe eosinophilic asthma receiving home benralizumab were stratified according to those who had received ≥3 doses prior to COVID-19 lockdown on the 15th March 2020 ('established' patients) versus those who were initiated after this date ('new' patients). We compared the last Asthma Control Questionnaire-6 (ACQ6) measured in clinic with that collected by telephone consultation 8-12 weeks after transition to homecare. Patients were excluded if both values were not available. Results: 246 benralizumab patients were included in the analysis, of whom 49 (20%) were new. There was no significant difference in pre-biologic ACQ6, pre-homecare (baseline) (Figure presented) ACQ6 or post-homecare ACQ6 between the new and established patient groups. Both cohorts exhibited a similar magnitude of improvement in their ACQ6 following the transition to homecare (-0.73 in the established group vs -0.73 in the new group, both P<0.0001) (figure 1). Conclusions: We have demonstrated that early transition to homecare in patients treated with benralizumab is not associated with worse clinical outcomes as assessed by ACQ6. The improvements in ACQ6 were seen irrespective of whether they were 'established' on therapy at time of transition or 'new'. Further research is required to understand the potential influence of lockdown and/or telephone vs face-to-face ACQ reporting.