Dissertation committee:
Παπίρης Σπυρίδων, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Λουκίδης Στυλιανός, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσαγκάρης Ηρακλής, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μπακάκος Πέτρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μάναλη Ευφροσύνη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ροβίνα Νικολέτα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παπαϊωάννου Ανδριάνα, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
PROTOCOL I
Introduction: Mepolizumab is a targeted, humanized anti–IL-5 monoclonal antibody that prevents IL-5 from binding to its receptor on eosinophils, and selectively inhibits eosinophilic inflammation and is approved for the treatment of severe eosinophilic asthma.
Aims / objectives: To determine the 2-year clinical experience, effectiveness, and safety of mepolizumab treatment for patients with severe eosinophilic asthma, in referral centers in Greece.
Methods: This is a prospective, multicenter, observational study, which was conducted in 22 different centers in Greece. The primary endpoint was to assess clinically significant asthma exacerbations (CSE) after 12 and 24 months of treatment respectively.
Results: 169 patients were eligible for the study (28% male, mean±SD age 57.7±12.6). 134 (79.3%) completed the 24-month follow -up. After a 2-year treatment there was 71.8% reduction (p<0.001) of CSE. At 24 months, there was a significant improvement in the ACT score from 15.2±4.5 to 21.8±3.1, and lung function as assessed by the increase in FEV1, from 1.87±0.7 to 2.2±0.8 L, p<0.001. OCS maintenance was significantly reduced from 10.6±7.5 mg/day to 1.7±3mg/day, p<0.001 at 24 months. Of note, 71% of those treated with OCS at baseline discontinued OCS altogether. According to the pre-defined Response Definition 1, 83.8% of patients were responders at 24 months and 19.6% were super-responders, and according to the Response Definition 2, 93.1% were responders at 24 months and 27.5% were super-responders. No significant safety issues were observed.
Conclusions: In this observational study mepolizumab was associated with significant reductions in the annual rate of exacerbations and maintenance OCS use, and improvement in asthma control and lung function that were maintained after two years of treatment.
PROTOCOL II
Objectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.
Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician’s global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.
Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).
Conclusion: Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.
Keywords:
Asthma, Omalizumab, Mepolizumab, Eosinophils, Severe asthma
