Clinical and economic impact of a one-year treatment with omalizumab in patients with severe allergic asthma within a drug programme in Poland

Although severe asthma applies to only 5 to 10% of patients with asthma, a substantial portion of the health care costs is associated with this phenotype of the disease [1‐3]. Only a small part of the cost is a result of diagnostic tests, which must be performed to differentiate severe asthma from other chronic diseases and to assess the impact of other diseases on the course of asthma. The greatest expenses are associated with treatment - an inadequate response to therapy, an inability to achieve sound asthma control and an increased risk of exacerbation – all of which result in additional high costs that affect health care utilization (HCU).

With the emergence of new data on the pathogenesis of asthma, the diversity of clinical presentations and the response to treatment, it is increasingly believed that severe asthma is a heterogeneous disease comprising discrete phenotypes that differ in pathogenesis, genetic background and clinical outcome [4, 5]. One of the phenotypes is allergic asthma.

OMB is a recombinant humanized monoclonal anti-IgE antibody designed to treat IgE-mediated disease by reducing the plasma concentration of free IgE antibodies. The efficacy and safety of OMB in severe persistent allergic asthma have been confirmed in numerous multicentre clinical trials [6, 7] where OMB as an add-on therapy reduced the number of asthma exacerbations and concomitant medication burden and improved symptom severity and quality of life (QoL) compared to the use of standard therapy alone.

The Global Initiative for Asthma (GINA) guidelines [8] recommended that OMB be considered an adjunctive therapy for patients with moderate or severe allergic asthma that is uncontrolled on step 4 of treatment. Per GINA, a stepwise approach is needed for adjusting asthma treatment to achieve good symptom control and minimize the future risk of exacerbations, fixed airflow limitation and medication side-effects. The choice of therapy may, however, be affected by the cost of treatment.

Innovative therapies (primarily biological therapies) in Poland are reimbursed within drug programmes [9]. A drug programme is “guaranteed compensation, including therapies with innovative, expensive active substances which are not financed by other guaranteed benefits. The treatment is carried out in selected disease entities and includes a strictly defined group of patients”. The advantage of carrying out treatment within drug programmes is more detailed qualification of patients recruited for treatment, based on well-described inclusion and exclusion criteria [10]. Check points allow, in turn, for a more detailed assessment of the efficacy, safety, and cost of the therapy.

Patients suffering from severe allergic asthma in Poland are treated within the drug program “Treatment of allergic, IgE-mediated asthma with omalizumab” [10]. This study evaluated the clinical outcomes and costs of add-on OMB therapy for severe allergic asthma in Poland based on a group of 85 patients who were the first to finish the one-year treatment.

This paper presents the trends in clinical outcomes, quality of life and costs of a one-year treatment with OMB in patients with severe allergic asthma for a cohort of patients who satisfied the inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB according to a set of objective criteria within a drug programme in Poland.

Drug programmes are one method of reimbursement, where patients are integrated into the treatment regimen of a clinical trial (inclusion and exclusion criteria) and then followed in daily practice.

Currently, 42 centres implement the drug programme. The treatment in the drug programme is carried out by physicians experienced in the diagnosis and treatment of severe persistent asthma and is 1restricted to patients prescribed systemic steroids (used chronically or during exacerbations) and for whom all other treatments have failed.

As shown in Poland, patients in this drug programme receive a significant clinical benefit from treatment with OMB, resulting from a reduction in the number of asthma exacerbations, enhanced disease control and improved QoL. There was also a significant decrease in the dose of oral corticosteroids. No clinical improvement was observed in only 3.5% of the severe asthma patients.

Many studies have confirmed the real-world evidence (RWE) of OMB treatment [13‐15].

The retrospective analysis of Barnes et al. [13] reported a lower number of exacerbations and enhanced QoL among British patients, consistent with previous studies of OMB. However, improved lung function and a reduction in annual steroid burden was greater in this study than in previous trials.

Findings from the 2-year eXpeRience registry agree with the results from randomized trials, indicating that OMB added to current therapy improves asthma control significantly among patients with uncontrolled persistent allergic asthma [14]. According to a physician’s GETE, 69.9% of patients responded to OMB after 16 weeks. While the percentage of patients with no clinically significant exacerbations was 6.8% during the 12-month pre-treatment period, this value increased to 54.1% at Month 12 and then to 67.3% at Month 24. Compared to the baseline, symptoms and the use of rescue medication decreased by > 50%. Furthermore, maintenance OCS use decreased from 28.6% at the baseline to 16.1 and 14.2% at Months 12 and 24, respectively. Overall, OMB was deemed to have an acceptable safety profile. To summarize, the eXpeRience registry findings are consistent with the results of the clinical trials and suggest that OMB is associated with improved outcomes among patients with uncontrolled persistent allergic asthma. As shown in the Cochrane database published in 2014, OMB was effective in reducing the number of asthma exacerbations and hospitalizations when used with inhaled steroids, as well as during steroid tapering phases of clinical trials [15]. Moreover, OMB was proven to facilitate reducing or withdrawing inhaled steroids more effectively than a placebo.

There is no doubt that the biological treatment of chronic diseases is cost-intensive. Therefore, the decision of the payer and regulator to implement this therapy must be balanced in each country.

In Poland, the drug programme description (with inclusion and exclusion criteria) and final decision on entry into the drug programme is made by the Ministry of Health based on a previous assessment of HTA (in Poland, the Agency for Health Technology Assessment and Pricing - AOTMIT) and the opinion of the Economic Committee, which is involved in negotiating drug prices.

This analysis demonstrated the trends in the costs of treating severe asthma with OMB in Poland within a drug programme. The most cost-intensive occurrence is exacerbation treated in a hospital (12,576.2 EUR), followed by improvement in asthma control (11,024.6 EUR), improvement in QoL (8607.3 EUR), exacerbation treated on an outpatient basis (5144.8 EUR) and lowering the dose of systemic glucocorticosteroids (2067.3 EUR).

It should be emphasized that the analysis presented in this study concerns the direct cost of severe asthma patient treatment with OMB in the drug programme.

This descriptive analysis on the basis of data from the Patient Registry in Poland provides an estimation of costs and outcomes for the defined group of patients with severe asthma, which could be used for the most advanced assessments of severe asthma treatment in Poland.

Unfortunately, the available data from this clearly defined cohort of patients in Poland do not allow one to calculate quality-adjusted life year (QALY) and the incremental cost-effectiveness ratio (ICER) as is recommended in pharmacoeconomic analyses.

There are numerous other publications that refer to QALY or ICER in this area [16‐22].

An economic evaluation in a Spanish RWE study was performed from the societal perspective, including direct health costs (resource use and drug treatments) and indirect costs (disease impact on labour productivity) in 2016 Euros (16). When only direct costs were included, the incremental cost-effectiveness ratios (ICERs) were 1487.46 EUR per exacerbation avoided and 5425.13 EUR per 3-point increase in ACT observed. When indirect costs were included, the ICERs were 1130.93 EUR per exacerbation avoided, and 4124.79 EUR per 3-point increase in ACT.

Campbell et al. concluded that adding OMB enhances quality-adjusted life years (QALY) while increasing direct medical costs. Their findings also indicated that using 16-week assessments to guide decisions regarding long-term treatment improves cost-effectiveness [17]. Dal Negro et al. reported that OMB treatment, while improving health-related QoL, increases costs significantly [18].

Youji Oba et al. evaluated the cost-effectiveness of OMB in adults and adolescents with moderate to severe allergic asthma and concluded that from a pharmacoeconomic point of view, considering the high cost and modest efficacy, it would be more beneficial to use OMB in allergic asthmatic patients with poorly controlled symptoms. They emphasized that this therapy would result in a cost reduction only if used among non-smoking patients who were hospitalized 5 or more times or 20 days or longer per year despite using maximal asthma therapy [19].

Van Nooten and Wu et al. assessed OMB treatment to not be cost-effective and reported ICERs of 38.371 EUR and 821.000 USD respectively (ICERs were per QALY gained). Van Nooten et al. concluded that OMB treatment was cost-effective. Moreover, data from the real-life 1-year randomized open-label study (ETOPA) that used Canada as a reference country reported an ICER of 31.209 EUR among patients with severe persistent allergic asthma [20, 21].

The work of Devilde and Oba et al. indicated OMB treatment to be cost-effective when used in patients with severe allergic asthma. These results suggest that to determine the cost-effectiveness of OMB treatment, asthma severity and the risk of asthma exacerbations should be investigated [19, 22].

With a willingness-to-pay (WTP) of 45.000 USD per QALY, OMB treatment was also not cost-effective in adults in Japan, but OMB treatment will continue to be an available treatment option due to its mechanism of action and benefits for severe asthma patients, particularly responders [23]. The cost-effectiveness of OMB treatment may be improved by confining therapy to groups of previously predicted responders and decreasing the price. For paediatric patients in Japan, cost-effectiveness is unclear and requires further study [24].

The interesting study of Faria et al. established the cost-effectiveness of OMB treatment under the list price and the Patient Access Scheme (PAS) discounted price for the UK National Health Service [25]. To assess the long-term cost-effectiveness of OMB treatment, a decision-analytics model was created. QALYs were used to measure the outcomes. Based on data from clinical trials, more specifically, previous hospitalization, maintenance OCS and three or more previous exacerbations, patient subgroups were created. The ICER cost-effectiveness ratio ranged from 30.109 GBP to 57.557 GBP per QALY gained depending on the population considered while using the PAS price; however, incremental cost-effectiveness ratios while using the list price were more than a third higher. The authors suggested that even though the cost-effectiveness of OMB treatment is more favourable under the PAS price, it only offers good value for the money when used in severe asthma patients and requires an optimistic outlook regarding asthma mortality and enhancing health-related QoL.

Recently published Canadian research has shown that OMB treatment was associated with higher costs ($ 1796 Can.) but not with a reduction in clinically important outcomes [26]. The authors suggested that OMB treatment has limited effectiveness in this study population and that future studies should further explore subsets of patients most likely to benefit from OMB therapy.

Considering the high cost of OMB therapy, special attention should be paid to studies assessing the possibility of safe discontinuation of the therapy, prolongation of the intervals between subsequent injections or a reduction in the OMB dose [27, 28]. The OMB dosing regimen should also be observed in real life for both clinical and economic assessment.

Because treatment with OMB in Poland is carried out in a framework of a drug programme, it is closely monitored, and the data are stored in a registry. Based on this registry, trends in clinical outcomes, quality of life and costs of treatments were assessed in a cohort of patients who satisfied the inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB treatment according to a set of objective criteria.

The clinical outcomes were highly improved. At the same time, the costs of treatment increased, mainly due to high OMB costs. Other costs associated with a decreased number of hospitalizations and ED and office visits and a reduction in OCS doses declined. It should be noted that even among patients who successfully respond to OMB, the cost of therapy remain high and is far from being offset by the reduction in adverse clinical outcome.These descriptive data can be used to further investigate and define patients who benefit the most from OMB treatment in clinical practice.