Real‐life effectiveness of biological therapies on symptoms in severe asthma with comorbid CRSwNP

Abstract Background We aimed to evaluate the effectiveness of different antibody therapies on nasal polyp symptoms in patients treated for severe asthma. Methods We performed a retrospective analysis of patients with severe asthma and comorbid CRSwNP who were treated with anti‐IgE, anti‐IL‐5/R or anti‐IL‐4R. CRSwNP symptom burden was evaluated before and after 6 months of therapy. Results Fifty patients were included hereof treated with anti‐IgE: 9, anti‐IL‐5/R: 26 and anti‐IL‐4R: 15 patients. At baseline median SNOT‐20 was similar among groups (anti‐IgE: 55, anti‐IL‐5/R: 52 and anti‐IL‐4R: 56, p = 0.76), median visual analogue scale (VAS) for nasal symptoms was 4, 7 and 8 (p = 0.14) and VAS for total symptoms was higher in the anti‐IL‐4R group (4, 5 and 8, p = 0.002). After 6 months SNOT‐20 improved significantly in all patient groups with median improvement of anti‐IgE: −8 (p < 0.01), anti‐IL‐5/R: −13 (p < 0.001) and anti‐IL‐4R: −18 (p < 0.001), with larger improvement in the anti‐IL‐4R group than in anti‐IgE (p < 0.001) and anti‐IL‐5/R (p < 0.001) groups. VAS nasal symptoms improved by median anti‐IgE: 0 (n.s.), anti‐IL‐5/R: −1 (p < 0.01) and anti‐IL‐4R: −3 (p < 0.001), VAS total symptoms by anti‐IgE: −1 (n.s.), anti‐IL‐5/R: −2 (p < 0.001) and anti‐IL‐4R: −2 (p < 0.001). Conclusions Treatment by all antibodies showed effectiveness in reducing symptoms of CRSwNP in patients with severe asthma, with the largest reduction observed in anti‐IL‐4R‐treated patients.


TO THE EDITOR
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe asthma 1 and shares key pathophysiological mechanisms including increased type 2-inflammation with secretion of IL-5, IL-4, IL-13 and IgE. Biological therapies, namely IgE-, IL-5/IL-5Rα -and IL-4Rα -antibodies have revolutionized the treatment of severe asthma and were recently also found to be effective in severe CRSwNP. [2][3][4] Here, we investigated the real-life effectiveness of different biologics on symptoms in patients with severe asthma and comorbid CRSwNP.
We performed a retrospective analysis of patients from LMU Munich severe asthma cohort included in the prospective German Asthma Net (GAN) registry who fulfilled inclusion criteria. The registry was approved by the IRB and all patients provided written informed consent. All patients fulfilled the diagnosis of severe asthma according to ERS/ATS guidelines. 5 Inclusion criteria: Patients with severe asthma and comorbid CRSwNP, who were initiated with monoclonal antibody therapy between 2018 and 2020 for whom data at baseline (−4 to 0 weeks before first antibody injection) and after 6 months (+/− 4 weeks) of antibody therapy were available. Current CRSwNP was defined as either a confirmed diagnosis by an ENT specialist, or typical nasal symptoms together with a CT scan evidencing nasal polyps and regular use of mometasone intranasally throughout the study period.
History of previous nasal polyp operations was self-reported. All patients received high-dose ICS/LABA +/− LAMA throughout the study, and some additionally oral corticosteroids (OCS, Table 1). Outcome measures at baseline and after 6 months included SNOT-20, 6 Visual Analog Scale (VAS) for nasal and total symptoms, Asthma Control Test (ACT) score, pulmonary function testing (Jäger, Body, Würzburg), and oral corticosteroid dosage. All antibodies were prescribed by the treating pulmonologist solely on clinical grounds during routine care for indication of severe asthma, respecting EMA prescription criteria as well as administration and dosing according to the manufacturer's instructions. If the patient fulfilled prescription criteria for several antibodies, initial antibody choice was up to the physician's and patient's preferences. Statistical analyses were performed using GraphPad Prism 8 (GraphPad Software).
In total, 60 patients with severe asthma and nasal polyposis who initiated therapy between 2018 and 2020 were identified, hereof 10 patients were not included in the analysis due to following reasons:  Table 1). Highest documented eosinophil count was significantly higher in patients treated with anti-IL-5/R and anti-IL-4R compared to the anti-IgE group (p = 0.0009, Table 1).
Moreover, patients treated with anti-IgE rarely had previous antibody therapy and mostly started treatment in spring and summer, whereas history of previous antibody therapy was frequent in the other groups and treatment start was distributed among all seasons (Table 1). At baseline median SNOT-20 was similar among groups (anti-IgE: 55, anti-IL-5/R: 52 and anti-IL-4R: 56, p = 0.76), median visual analoge scale (VAS) for nasal symptoms was 4, 7 and 8 (p = 0.14) and VAS total symptoms was higher in the anti-IL-4R group (4, 5 and 8, p = 0.002, Table 1). Median baseline ACT score was 14, 14 and 20, respectively (p = 0.12, Table 1).
We found that treatment with anti-IgE, anti-IL-5/R and anti-IL-4R while improving asthma outcomes, also all significantly reduced the symptoms of CRSwNP measured by SNOT-20, supporting the "one airway concept" that assumes similar pathomechanisms in CRSwNP and asthma. 7 Recent trials in severe CRSwNP have shown T A B L E 1 Baseline characteristics of the study population according to treatment group. Data are displayed as mean +/− SD when normally distributed and otherwise median (IQR). Statistics by ordinary one-way ANOVA or Kruskal-Wallis ANOVA as appropriate   *Switch anti-IL5 to anti-IL5R.