The cost-effectiveness of OM-85 in managing respiratory tract infections in China

Abstract

Objectives:

To demonstrate the health economic impact of OM-85, a bacterial lysates based immunostimulant, for its approved indications in China.

Methods:

A cost-effectiveness decision tree model was constructed comparing OM-85 with the best supportive care/placebo therapy for managing the acute exacerbation of chronic bronchitis and rhinosinusitis in the Chinese population. Clinical efficacy and adverse events (AE) data were included in the model based on a thorough literature review. All localized direct treatment costs, including drug cost, AE costs, and medical treatment costs for underlining diseases were included from a Chinese third party payer perspective. A Key Opinion Leaders (KOL) survey was conducted with 20 senior physicians specialized in respiratory, ENT, allergy, and immunology fields from tertiary hospitals in Beijing, Shanghai, Guangzhou, Hangzhou, Shenyang, and Wuhan to validate the local treatment costs. Incremental cost-effectiveness ratio (ICER) was calculated based on the above efficacy and cost information.

Results:

OM-85 is a cost-effective therapy when compared with placebo (standard care). OM-85 can treat/prevent one additional full episode exacerbation of chronic bronchitis and one additional full episode exacerbation of rhinosinusitis with only additional costs of RMB 653 and RMB 1182.84, respectively. In comparison, each acute exacerbation of chronic bronchitis will cost RMB 4510.10, and each acute exacerbation of rhinosinuisitis will cost RMB 1807.21 in a Chinese clinical management setting. One-way sensitivity analyses were performed and the ICER result was demonstrated to be consistent.

>Conclusions:

OM 85 reduces acute exacerbations among patients with chronic bronchitis and chronic rhinosinusitis when compared with Placebo (standard care). From a Chinese payer perspective, OM 85 is a cost-effective therapy in the clinical management of both chronic bronchitis and rhinosinusitis in the adult population.

Keywords::

• Respiratory tract infections
• Chronic bronchitis
• Cost-effectiveness
• China

Introduction

Immunity to infections can be achieved as a result of natural processes following infection or as the result of medical treatments, including immunostimulants and immunoglobulins1. Some immunostimulants, which can be extracted from bacteria, have been shown to induce a non-specific response, a combination of cellular (B- and T-cell stimulation) and humoral responses (production of antibodies and cytokines) without exposing the patient to infection. Although such immunomodulatory activity is similar to what is caused by naturally-occurring pathogens, the immune response induced by bacterial immune-stimulants is subtle compared to the response to real pathogenic bacteria.

Most acute exacerbations in chronic bronchitis or chronic obstructive pulmonary disease (COPD) are due to respiratory tract infections. OM-85 (brand name is Broncho-Vaxom), a lysate comprising eight bacterial species and sub-species frequently responsible for respiratory infections2, stimulates the immune system to increase the body’s natural defenses against a wide spectrum of respiratory pathogens. It also prevents or reduces the severity of acute exacerbations (AE) of chronic bronchitis and recurrent infections of the respiratory tract, in particular rhinosinusitis, rhinopharyngitis, and otitis media in adults and children2^,3.

Chronic rhinosinusitisis, another respiratory disease that has high prevalence, impacts patients’ quality-of-life significantly and results in considerable economic loss4. Clinical studies have shown that OM-85 improves symptoms and prevents acute episodes effectively in patients with chronic purulent sinusitis5^,6.

OM-85 contains parts of lysates from bacteria responsible for common respiratory tract infections: Hemophilusinfluenzae, Streptococcus pneumoniae, Klebsiellapneumoniae, Klebsiellaozaenae, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus sanguinis, and Moraxella catarrhalis. OM-85 acts on both innate immunity and adaptive immunity. It is given orally to treat and prevent respiratory tract infections in adults and children2^,3. In vitro studies have shown that OM-85 has a significant impact on macrophages activity, notably by inducing the release of oxidative metabolite like nitric oxide7. In vivo studies have shown an increase in pathogen destruction through the increase of macrophage activity8. OM-85 also stimulates the activity of T and B lymphocytes indirectly in vivo by increasing cytokine expression, which in turn stimulates the immune response9.

Heintz et al.5 showed that OM-85 controlled symptoms and nasal discharge of patients with chronic purulent sinusitis more effectively than placebo. Other clinical studies have shown that OM-85 improves symptoms, reduces the convalescence period, and lowers the rate of recurrence significantly among adults and children with sub-acute sinusitis10. OM-85 has also been shown to reduce the risk of acute exacerbations among patients with chronic bronchitis and mild COPD11.

Several economic evaluations of OM-85 have been completed. Bergemann et al.12 found that using OM-85 to prevent acute exacerbations in chronic bronchitis was cost-saving. Collet et al.13 estimated the incremental cost to prevent one day of hospitalization for a respiratory condition at CDN $45, and concluded that the use of an immunostimulating agent may decrease the financial burden of acute exacerbations in patients by reducing the severity of episodes and, therefore, the number of hospitalizations and the length of hospital stay per patient13.

Respiratory diseases, which are mainly of infectious origin, are the third leading cause of death in rural areas and the fourth leading cause of death in urban areas, accounting for 1 million deaths and over 5 million disabilities each year in China14. No previous published study has evaluated the cost-effectiveness of OM-85 for respiratory infections in the Chinese setting.

The primary objective of this study is to evaluate the cost-effectiveness of OM-85 in managing respiratory tract infections in the Chinese adult population via decision-tree modeling.

Methods

Model design

The target population is composed of Chinese adult patients diagnosed with chronic bronchitis or rhinosinusitis. We used decision-analytical techniques to estimate the cost-effectiveness of OM-85 as compared to standard care therapy (labeled placebo in the model) in the Chinese setting. The decision tree constructed is shown in Figure 1. The analysis was done from a third-party payer perspective and the time horizon considered was 6 months.

Figure 1. The decision-analysis model.

A decision-tree model was constructed to evaluate the cost and effectiveness of OM-85. In the model, we consider the likelihood of acute exacerbation or infectious events with and without prophylaxis. We compared the two strategies by estimating the incremental cost-effectiveness ratio based on the incremental effectiveness of OM-85 in terms of preventing recurrent infections and acute episodes and the incremental cost of OM-85 treatment. The incremental cost-effectiveness ratio was calculated by dividing the incremental cost by the incremental effectiveness. Effectiveness was expressed as acute exacerbations or recurrent infectious events avoided.

Effectiveness of OM-85

A literature review was performed to identify the following data components: prevalence of various identified respiratory tract infections in the Chinese population, clinical efficacy of OM-85 in the management of acute exacerbations of chronic bronchitis and rhinosinusitis, and detailed data on adverse events associated with OM-85 treatment. Because data on adverse events was not available in the published literature, we obtained information from the label approved by Chinese regulatory authorities. Efficacy data are summarized in Table 1. OM-85 lowered the rate of acute exacerbation in chronic bronchitis patients by 24% and the rate of acute rhinosinusitis by 65%, when compared with placebo. The tolerability profile of OM-85 was similar to the placebo.

Table 1. Efficacy and tolerability of OM-85 and placebo in treating and preventing acute exacerbations of chronic bronchitis or treating rhinosinusitis.

	OM-85	Placebo
Efficacy
Rate of acute exacerbation  of CB11	0.71 episodes	0.93 episodes
Rate of acute sinusitis5	7%	20%
Adverse event*
Nausea	1.3%	1.3%
Vomiting	4.5%	4.6%
Diarrhea	5.7%	5.7%
Upper abdominal pain	1.4%	1.3%
Urticaria	0.6%	0.6%
Swelling	0.1%	0.1%
Eczema	0.8%	1.0%
Cough	5.3%	5.6%
Nasopharyngitis	4.0%	4.1%
Laryngitis	0.8%	0.5%
Sinusitis	2.7%	3.2%
Bronchitis	7.7%	6.6%
Asthma	1.1%	1.3%
Fever >39° C	4.9%	4.9%
Immune response	0.4%	0.2%

*The incidence of adverse events is taken from the OM-85 label.

Resource use and cost inputs

Because the primary perspective of this analysis is a third-party payer, costs include direct medical costs associated with the treatment options. Indirect costs, such as patients’ travel costs and productivity changes were not considered. Quantities of resources used were identified from a literature review and from local experts. A structured questionnaire was developed and administered to 20 local healthcare experts from tertiary hospitals in China, with a balanced geographic distribution, to collect information on the resource use and cost data not available in published literature. These experts provided information on doses and dose regimens for OM-85, examination procedures, frequency of adverse events, and other resources used. Unit cost data were extracted from published literature, including government-issued price and reimbursement documents. All cost data were converted to 2014 values in RMB.

Based on the cost data collected, we estimated treatment cost and the cost related to the management of complication and/or exacerbation in each treatment arm. The cost of OM-85 is based on the available retail price of RMB 128 per pack (7 mg capsule × 10), i.e. RMB 1.83 per mg. The dosage is one capsule per day for adults for 10 days each month for 3 months so the total seasonal cost of the drug (for 6 months’ treatment) is ∼RMB 386 for adults. Other cost data for the model are presented in Table 2.

Table 2. Costs of treating acute exacerbations of chronic bronchitis and related adverse events.

Item	Average cost/episode (RMB)
Chronic bronchitis acute exacerbation*	4510.10
Acute sinusitis*	1807.21
Other AE costs*
Nausea	5.71
Vomiting	5.71
Diarrhea	5.71
Upper abdominal pain	4.67
Urticaria	9.05
Swelling	4.76
Eczema	5.71
Cough	4.29
Nasopharyngitis	3.81
Laryngitis	1.43
Sinusitis	4.76
Bronchitis	4.76
Asthma	22.38
Fever >39° C	477.14
Immune response	476.43

*Based on expert survey.

Analysis

The analysis was done on a sample of one patient in each treatment arm. The discount rate applied to both cost and benefit is 3.0%. One-way sensitivity analyses were performed by varying drug cost (±10%), the rate of acute exacerbation (±10%) and the rate of acute sinusitis episodes (±10%) to extreme values.

Results

Cost-effectiveness results for the base-case scenario with an adult population for chronic bronchitis indication is presented in Table 3. In treating and preventing acute exacerbations of chronic bronchitis, total costs were RMB 825 for the OM-85 arm and RMB 681 for the placebo arm. The number of acute exacerbations was 0.70 for the OM-85 arm and 0.92 for the placebo arm. Thus, the incremental cost-effectiveness ratio predicted by our model is RMB 653.27 per acute exacerbation avoided. This suggests that OM-85 is a cost-effective therapy. It means that OM-85, when compared with placebo arm, can prevent one additional episode exacerbation of chronic bronchitis with only RMB 653 extra costs. In comparison, each acute exacerbation of chronic bronchitis will cost RMB 4510.10 in a Chinese clinical management setting.

Table 3. Cost-effectiveness for OM-85 vs placebo (Chronic bronchitis indication).

	OM-85 (RMB)	Placebo (RMB)	Difference
Total costs	825.13	681.41	143.72
CBAE cost	55.89	59.46	−3.57
Drug cost	385.07	0.00	385.07
All other cost (including COPD15 and AEs*)	384.17	621.95	−237.78
COPD cost	357.42	595.70	−238.28
Nausea	0.07	0.08	0.00
Vomiting	0.25	0.26	−0.01
Diarrhea	0.32	0.32	0.00
Upper abdominal pain	0.07	0.06	0.01
Urticaria	0.05	0.05	0.00
Swelling	0.00	0.01	0.00
Eczema	0.04	0.05	−0.01
Cough	0.23	0.24	−0.01
Nasopharyngitis	0.15	0.16	0.00
Laryngitis	0.01	0.01	0.00
Sinusitis	0.13	0.15	−0.02
Bronchitis	0.36	0.31	0.05
Asthma	0.24	0.30	−0.06
Fever (>39° C)	22.94	23.18	−0.24
Immune response	1.89	1.09	0.80
Number of exacerbation	0.70	0.92	0.22
Incremental cost-effectiveness ratio (RMB/per acute exacerbation avoid)	653.27

CBAE, Chronic bronchitis acute exacerbation.

*Based on expert survey.

Cost-effectiveness results for the base-case scenario with adult population for rhinosinusitis indication is presented in Table 4. In preventing acute exacerbations of rhinosinusitis, total costs were RMB 537.23 for the OM-85 arm and RMB 383.46 for the placebo arm. The number of episodes of rhinosinusitis was 0.07 for the OM-85 arm and 0.20 for the placebo arm. Thus, the incremental cost-effectiveness ratio predicted by our model is RMB 1182.84 per full sinus case avoided. This suggests that OM-85 is a cost-effective therapy. It means that OM-85, when compared with placebo arm, can prevent one additional episode exacerbation of rhinosinuisitis with only RMB 1182.84 extra costs. In comparison, each acute exacerbation of rhinosinuisitis will cost RMB 1807.21 in a Chinese clinical management setting.

Table 4. Cost-effectiveness for OM-85 vs placebo (Rhinosinusitis indication).

	OM-85 (RMB)	Placebo (RMB)	Difference
Total costs	537.23	383.46	153.77
Rhinosinusitis cost	125.41	358.30	−232.90
Drug cost	385.07	0.00	385.07
AE total cost	26.75	25.16	1.59
Nausea	0.07	0.08	0.00
Vomiting	0.25	0.26	−0.01
Diarrhea	0.32	0.32	0.00
Upper abdominal pain	0.07	0.06	0.01
Urticaria	0.05	0.05	0.00
Swelling	0.00	0.01	0.00
Eczema	0.04	0.05	−0.01
Cough	0.23	0.24	−0.01
Nasopharyngitis	0.15	0.16	0.00
Laryngitis	0.01	0.01	0.00
Sinusitis	0.13	0.15	−0.02
Bronchitis	0.36	0.31	0.05
Asthma	0.24	0.30	−0.06
Fever (>39° C)	22.94	23.18	−0.24
Immune response	1.89	1.09	0.80
Number of full sinuses	0.07	0.20	0.13
Incremental cost-effectiveness (RMB/per full sinus case avoid)			1182.84

In the one-way sensitivity-analyses, we calculated the total cost of each treatment arm by varying drug cost to ±10% of the base-case cost. We also calculated effectiveness (the number of exacerbations) by varying rates of exacerbation to ±10% of the base-case rate. The results of our sensitivity analysis are summarized in tornado diagrams (Figures 2 and 3).

Figure 2. Changes in ICER in the sensitivity analyses on drug costs and rate of acute exacerbation of chronic bronchitis.

Figure 3. Changes in ICER in the sensitivity analyses on drug costs and rate of acute exacerbation of sinusitis.

Discussion

OM-85 is an effective approach with a good tolerability profile for the management of acute exacerbation of chronic bronchitis3 and acute infections in chronic purulent sinusitis5. It has been shown to be cost-saving in preventing recurrent rhinopharyngitis among children in a French setting13, and it has been shown to be cost-saving12 or cost-effective16 in preventing severe acute exacerbations in patients with chronic bronchitis in Italy and Canada. This study provides the first cost-effectiveness analysis on OM-85 in preventive treatments for patients with chronic bronchitis or rhinosinusitis in China.

Our study demonstrated that OM-85 is a cost-effective therapy. When compared with placebo (standard care), OM-85 can treat/prevent one additional full episode exacerbation of chronic bronchitis and one additional full episode exacerbation of rhinosinusitis with only additional costs of RMB 653 and RMB 1182, respectively. In comparison, each acute exacerbation of chronic bronchitis will cost RMB 4510.10 and each acute exacerbation of rhinosinuisitis will cost RMB 1807.21 in a Chinese clinical management setting.

It was noted that the incremental cost-effectiveness ratio of treating/preventing chronic bronchitis is more sensitive to the change in rate of acute exacerbation than to changes in drug cost. The incremental cost-effectiveness ratio of treating/preventing rhinosinuisitis is more sensitive to changes in drug cost than to the change in rate of full sinuses. Our findings in the Chinese setting are consistent with pharmacoeconomic studies in French, Italian, and Canadian settings5^,10^,13. Two limitations of the present study should be noted. As with similar studies, our conclusions depend on the cost of OM-85 and the cost of treatment of exacerbations and acute sinusitis. Second, some cost inputs are based on the opinions of the experts surveyed. Although these experts were balanced geographically, the generalizability of the cost estimate requires further investigation.

Conclusions

This study found that treatment with OM-85 reduces acute exacerbations among patients with chronic bronchitis and chronic rhinosinusitis when compared with Placebo (standard care). From a Chinese payer perspective, OM-85 is a cost effective therapy in the clinical management of both chronic bronchitis and rhinosinusitis in the adult population.

Transparency

Declaration of funding and financial relationships

This study was sponsored by Vifor Pharmaceuticals.

Declaration of financial relationships

No authors are employees of Vifor Pharmaceuticals. No authors own Vifor Pharmaceuticals stocks at the time the study was conceived and conducted. In addition, JME Peer Reviewers on this manuscript have no relevant financial relationships to disclose.