Real‐world Omalizumab and Mepolizumab treated difficult asthma phenotypes and their clinical outcomes

Abstract

Background Omalizumab and Mepolizumab are biologic drugs with proven efficacy in clinical trials. However, a better understanding of their real‐world effectiveness in severe asthma management is needed. Objectives To better understand the real‐world effectiveness of Omalizumab and Mepolizumab, elucidate the clinical phenotypes of patients treated with these drugs, identify baseline characteristics associated with biologic response and assess the spectrum of responses to these medications. Methods Using real‐world clinical data, we retrospectively phenotyped biologic naïve patients from the Wessex AsThma CoHort of difficult asthma (N = 478) commenced on Omalizumab (N = 105) or Mepolizumab (N = 62) compared to severe asthma patients not receiving biologics (SNB, N = 178). We also assessed multiple clinical endpoints and identified features associated with response. Results Compared to SNB, Omalizumab patients were younger, diagnosed with asthma earlier, and more likely to have rhinitis. Conversely, compared to SNB, Mepolizumab patients were predominantly older males, diagnosed with asthma later, and more likely to have nasal polyposis but less dysfunctional breathing. Both treatments reduced exacerbations, Acute Healthcare Encounters [AHE] (emergency department or hospital admissions), maintenance oral corticosteroid dose, and improved Asthma Control Questionnaire 6 (ACQ6) scores. Omalizumab response was independently associated with more baseline exacerbations (p = .024) but fewer AHE (p = .050) and absence of anxiety (p = .008). Lower baseline ACQ6 was independently associated with Mepolizumab response (p = .007). A composite group of non‐responders demonstrated significantly more psychopathologies and worse baseline subjective disease compared to responder groups. Conclusions and Clinical Relevance In a difficult asthma cohort, Omalizumab and Mepolizumab were used in distinct clinical phenotypes but were both multidimensionally efficacious. Certain baseline clinical characteristics were associated with poorer biologic responses, such as psychological co‐morbidity, which may assist clinicians in biologic selection. These characteristics also emphasize the need for comprehensive approaches to support these patients.

Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence

“…On the other hand, in severe patients in which OCS resistance is proved by a high daily dose intake, the current pharmacological armamentarium based on the use of mAbs permits reversion of OCS dependence, leading to the suspension of OCS therapy in most patients or a reduction in the daily dose greater than 50% in those subjects affected by very severe forms of asthma. In any case, the overall current real-world findings and data from specific long-term investigations [88][89][90][91] indicate that the level of the OCS-sparing effect and the reversion of OCS dependence is an effect of the mAbs class, regardless of the specific target modulated by each compound. This evidence is in agreement with the position of the current recommendations [1], which do not support one specific mAb against the others for use as an OCS-sparing agent at GINA step 5.…”

“…Six studies were carried out on benralizumab [34][35][36][37][38][39], 1 on dupilumab [40], 18 on mepolizumab [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58], 27 on omalizumab [18,, and 3 on reslizumab [85][86][87]. Four studies investigated different mAbs in the same report [88][89][90][91]. The main characteristics of the real-world studies included in this systematic review are reported in Table 1.…”

Recent Insights into the Management of Inflammation in Asthma

“…It is though important to recognise that some patients don't respond to T2-biologics as recently shown by real-world studies like WATCH. 26 Understanding the mechanisms behind such failed responses will be a matter for future research focus.…”

“…209 Real-world studies have shown that the typical patients receiving Omalizumab are younger in age, have earlyonset asthma, and had a higher reported history of co- OCS requirements [264][265][266][267][268] morbid atopic conditions such as allergic rhinitis. 20,26 The multidimensional clinical efficacy of Omalizumab in such patients has been shown in meta-analyses of clinical trials. 210 Similarly, in meta-analyses of real-world observational studies, Omalizumab response rates are around 77%, 211 with associated significantly improved exacerbation rate, FEV 1 , oral corticosteroid use, and health care utilisation.…”

“…224 Indeed, we have previously shown that around 40% of Omalizumab treated patients potentially qualify for Mepolizumab, had it been available at the time. 26 Furthermore, there have been emerging real-world data on biologic switching from anti-IgE to anti-eosinophil agents 225,226 in dual-eligible patients who did not respond to Omalizumab. This includes a real-world multicentre clinical trial (OSMO) 227 where switching has shown to not only be safe, but also efficacious in improving asthma control, healthcare utilization and exacerbations, even without an Omalizumab washout period.…”