1. Background
Tiotropium bromide Soft Mist Inhaler (Spiriva Respimat; Tio R 5) is a long-acting muscarinic antagonist (LAMA) indicated as a long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema, and for the reduction of exacerbations.1 The manufacturer is requesting a listing in line with the indication. Tio R 5 is available as a multi-use cartridge containing 60 2.5 mcg actuations. As the recommended dose of Tio R 5 is two inhalations of 2.5 mcg (5 mcg) once daily, each cartridge provides a 30-day supply. At the confidentially submitted price of ▬ per cartridge, Tio R 5 costs ▬ daily.
2. Summary of the Economic Analysis Submitted by the Manufacturer
The manufacturer submitted a cost-comparison analysis2 considering Tio R 5 primarily with 18 mcg once-daily tiotropium bromide dry powder inhaler (Spiriva HandiHaler; Tio H 18) as well as with 50 mcg once-daily glycopyrronium (Seebri Breezhaler) and 400 mcg twice-daily aclidinium bromide (Tudorza Genuair), the other individual LAMA inhalers currently available in Canada. The perspective was that of a publicly funded Canadian drug plan with a time horizon of one year. Only drugs costs were included.
Ontario Drug Benefit (ODB) Formulary list prices (October 2014) were used to estimate comparator costs. Similar pharmacokinetic exposure, efficacy, and safety between Tio R 5 and Tio H 18 were assumed on the basis of two 4-week crossover trials3 and the long-term (2.3 years) TIOSPIR safety trial.4–6 No evidence was submitted regarding the clinical similarity between Tio R 5 and aclidinium bromide or between Tio R 5 and glycopyrronium.
The manufacturer concluded that Tio R 5 would lead to a savings of ▬ per patient annually when compared with Tio H 18 when an 8% markup was included, or ▬ without the markup. At the submitted price, Tio R 5 is ▬ compared with the current ODB or Alberta Health list prices for glycopyrronium and aclidinium bromide.
3. Key Limitations
3.1. Clinical Similarity to Some Comparators Uncertain
While head-to-head trials exist comparing the clinical efficacy7 and safety4–6 of Tio R 5 with Tio H 18, there are currently no trials available that compare Tio R 5 with glycopyrronium or aclidinium bromide. Mixed-treatment comparisons exist8,9 that compare Tio R 5 with other LAMAs as well as with long-acting beta-2 agonists (LABAs), inhaled corticosteroids (ICS)/LABA combinations, and placebo for outcomes of COPD exacerbations and mortality; however, limitations within these studies and the inconsistency of their results with those of the TIOSPIR trial suggest that the results should be interpreted with caution (see CADTH Common Drug Review [CDR] Clinical Report, Appendix 6). The clinical similarity of Tio R 5 to glycopyrronium and aclidinium bromide is uncertain; thus, whether Tio R 5 represents ▬ treatment is also uncertain.
3.2. Appropriate Comparators Omitted
While the other LAMA products are the most direct comparators to Tio R 5, current COPD guidelines10,11 also recommend LABAs or ICS/LABAs as appropriate alternatives to LAMA therapy for some patients within the approved indication for Tio R 5. CDR compared the annual cost per patient of Tio R 5 with that of the available LABA and ICS/LABA products. At the submitted confidential price, Tio R 5 is less expensive than all ICS/LABA fixed-dose combinations, but more expensive than some LABA-only products (Table 3).
4. Issues for Consideration
4.1. Patients Requiring Double Therapy
While Tio R 5 is ▬ ▬ ▬ compared with other single-drug LAMA inhalers for patients requiring10,11 a LAMA plus a LABA combination therapy, any combination of Tio R 5 with an individual LABA product is more expensive than the currently available LAMA/LABA combination inhalers (see Table 4).
4.2. Ease of Use/Device Preference
There is evidence that at least some patients using tiotropium bromide prefer the Respimat Soft Mist Inhaler to the HandiHaler dry powder device (see CDR Clinical Report, Appendix 7, for details).
4.3. Upcoming Comparators
While Tio R 5 is ▬ ▬ ▬ compared with currently marketed LAMA inhalers for COPD, new LAMA products (e.g., umeclidinium bromide) are currently under review by CDR and the prices are currently not disclosed. Consequently, the relative cost of Tio R 5 to newly approved LAMAs is unknown.
5. Results and Conclusions
At the submitted confidential daily cost of ▬, the use of Tio R 5 is less expensive per patient annually (▬ without markup) than the current list price of Tio H 18 and ▬ glycopyrronium and aclidinium bromide. Tio R 5 is also less expensive than available ICS/LABA combination products, but is more expensive than some individual LABA products. For patients requiring LAMA plus LABA therapy, currently available LAMA/LABA fixed-dose combinations ▬ ▬ ▬ possible combinations of Tio R 5 plus a LABA.
6. Cost-Comparison Table
Clinical experts have deemed the comparator treatments presented in to be appropriate. Comparators may be recommended (appropriate) practice versus actual practice. Comparators are not restricted to drugs, but may be devices or procedures. Costs are manufacturer list prices, unless otherwise specified. Additional drugs for COPD can be found in Appendix 2.
Cost-Comparison Table for LAMAs, LABAs, and Combinations for COPD.
