Effectiveness of the Polish program for the treatment of severe allergic asthma with omalizumab: a single-center experience

Patients were evaluated at baseline and after 16 weeks of the treatment in compliance with program requirements contained in the Appendix to the Minister of Health Declaration [3]. On entering the program, a detailed history was collected from each patient, concerning sensitizations, asthma control, exacerbations, pharmacotherapy, complications induced by systemic steroid therapy, and smoking. Each patient underwent resting spirometry, skin prick tests (SPT) when possible, and laboratory tests (including total serum IgE levels, and optionally to SPT, allergen-specific IgE (sIgE) tests), All patients completed the Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ). Moreover the mean daily dose of OCS over the last 6 months, the number of hospitalizations, and the number of severe exacerbations in the previous year were calculated. Monthly exacerbation rate was calculated according following formula: number of exacerbations/months of observations. At the 16^th week, early effectiveness was assessed based on the improvement in ACQ and AQLQ scores, severe exacerbations rate, and mean daily dose of OCS. Finally, doctors in charge used a five-point global effectiveness of treatment evaluation (GETE) scale to assess OMA treatment response in our patients, as outlined previously [5]. The early effectiveness was evaluated only in patients who de novo received omalizumab to avoid the influence of the previous treatment on the results.

For inclusion in the OMA program, patients must meet all major qualifying criteria, and a minimum of three minor criteria (from a total of six) of severe uncontrolled allergic bronchial asthma as defined by the NHF (Table 1). The major criteria qualifying patients for the OMA program include: ICS > 1000 mcg/day plus another control drug, and a minimum 5 mg/day of OCS (calculated as a mean dose over the 6 previous months). The minor criteria include: ≥ 3 severe exacerbations in the previous year, hospitalization due to exacerbations in the previous year, a history of life-threatening exacerbations of asthma, ACQ score > 1.5 points, AQLQ score < 5 points, and forced expiratory volume in one second (FEV1) < 60 % predicted.

The study was conducted in accordance with the Declaration of Helsinki [6], and local regulations relating to observational studies. Patients entering the NHF program gave written consent to participate in the program under specific terms for obtaining the medical history, performing the physical examination or additional tests (i.e., lung tests, blood tests, ACQ, AQLQ), and data collection. These terms are described in the Appendix to the Minister of Health Declaration [3]. In addition, patients gave written consent prior to each time the drug was administered, according to the formula developed by the Coordinating Board at the NHF. The study is based on the analysis of data collected prospectively in the program. The source data were encrypted and the extracted data were anonymous. The authors obtained the consent for the study from the ethics committee at the Medical University of Lodz.

In total, 20 men and 33 women, with a mean age of 46 years, were included in the study. The detailed demographic and clinical data are presented in Table 2. Briefly, the average duration of severe asthma in patients enrolled for the program was 13 years. Allergies were confirmed by the SPT or sIgE tests, and revealed that the house dust mite was the most frequently sensitizing allergen (50/53 patients, 94 %) followed by cat allergen (36/53 patients, 68 %). The mean ICS dose converted to beclomethasone CFC (BDP-CFC) equivalent was 2900 mcg/day, and the mean OCS dose in prednisone equivalent was 16 mg/day (note: the mean was calculated from data over the previous 6 months). In the year preceding enrolment, the mean number of exacerbations in the group was 5.4/year, and 24 patients (45 %) were hospitalized due to exacerbations.

All patients showed high mean daily dose of OCS at the baseline (Table 2, Fig. 1). Patients most frequently met 4/6 (47.2 %) of the minor criteria (Fig. 1). The most frequently fulfilled minor criteria were: ACQ score > 1.5 points, exacerbations ≥ 3 in the previous year, and AQLQ score < 5.0 points (Fig. 1). The percentage of patients who met each particular criterion of severe uncontrolled allergic bronchial asthma is shown in Fig. 1. The OMA doses for patients participating in the program were determined according to the manufacturer’s recommendations and the drug characteristics (Fig. 1).

Early effectiveness analysis was conducted in de novo patients only. After 16 weeks, 16/23 (70 %) new patients treated with OMA were evaluated. One patient failed to attend the two subsequent meetings and we have lost contact with her, while the other six patients only received OMA treatment for a period shorter than 16 weeks. The evaluation of the effectiveness of the 16-week therapy was carried out in compliance with the program requirements. All patients showed good (15/16, 94 %) or excellent (1/16, 6 %) response to the therapy based on the GETE scale (Table 3). In addition, all patients (100 %) had a decreased number of exacerbations (Table 3). These two criteria are obligatory to warrant ongoing OMA treatment. When evaluating the additional clinical criteria for clinically significant improvement, we found 14/16 (88 %) patients showed a significant reduction (P = 0.0001) in OCS use by at least 5 mg (Fig. 2, Table 3). In 15/16 (94 %) patients, the ACQ score was significantly reduced (P = 0.0012) by at least 0.5 points, and in 14/16 (88 %) patients, the AQLQ score was significantly improved (P = 0.0055) by at least 0.5 points (Fig. 2, Table 3). Of these additional criteria, 100 % of patients met at least two out of the three criteria, and all criteria (3/3) were met by 13/16 patients (81 %). Finally, 8/16 (50 %) patients achieved a clinical improvement in lung function, i.e., showed a ≥ 200 ml improvement in the FEV1, although for whole group the increase in FEV1 was not statistically significant (P = 0.5521) (Fig. 2, Table 3).

At the time of the program implementation in the Barlicki University Hospital, 31 patients with asthma were receiving OMA treatment. While applications for therapy continuation were submitted for all patients, 11 patients were disqualified as their OMA duration had exceeded 36 months. However, in 9/11 (82 %) patients, OMA treatment was reintroduced due to worsening of asthma control. One patient did not develop severe exacerbation, despite worsening of asthma control. Another patient, with severe exacerbation, did not arrive for the final visit of the qualification procedure. A detailed analysis of this group of patients was presented previously [7].

Twelve patients were admitted to the program temporarily (until they reached a total of 36 months of treatment). Three of these 12 patients have now finished OMA treatment. In 2/3 (67 %) patients who finished the treatment, worsening of asthma control and severe exacerbations were recorded upon OMA cessation. These patients went through the qualification procedure again; one has been given consent for further treatment and another one is waiting for consent. The third patient has failed to communicate with us.

Overall 11/14 (79 %) patients whose OMA therapy was interrupted after ≥ 36 months of treatment showed worsening of asthma control and severe exacerbations.

The dataset supporting the conclusions of this article is presented within the article. The detailed clinical data set is not publically available to protect research subject privacy and confidentiality.