Fixed-Dose Combination Therapy for COPD: Why One Size Does Not Fit All?

 In COPD

Fixed-dose combination therapy offers convenient dosing and improves compliance; however, their place in hospice therapy is limited and these novel inhalers are expensive. This article will discuss new fixed-dose combination therapies, their limitation and the cost-effective alternative for hospice patients.

LAMA/LABA combination

Inhaled bronchodilators are the cornerstone of treatment in COPD. Both long-acting muscarinic antagonists (LAMAs) and long- acting beta 2-adrenergic agonists (LABAs) are used as long-term maintenance treatment of airflow obstruction in patients with COPD. The fixed-dose combination inhalers are designed to provide extra bronchodilation compared with either therapy alone. Currently, Anoro Ellipta (umeclidinium-vilanterol) and Stiolto Respimat (tiotropium-olodaterol) are the only FDA approved LAMA/LABA combinations available on the market that may be given in a convenient once daily dosing.

Two new LAMA/LABA combination inhalers received FDA approvals but not yet available on the market. Utibron Neohaler (glycopyrrolate-indacaterol) and Bevespi Aerosphere (glycopyrrolate-formoterol), approved in Oct 2015 and April 2016, respectively, offer another option of LAMA/LABA dual combination bronchodilator to patients with COPD. Both inhalers contain the same long-acting muscarinic antagonist, glycopyrrolate, with the different LABAs (indicaterol versus formoterol). Both of these new inhalers are given twice daily.

One of the notable differences between all of these products is the type of inhalation device used. Anoro Ellipta and Utibron Neohaler deliver medication via a dry powder inhaler whereas Stiolto Respimat and Bevespi Aerosphere use a metered-dose inhaler. Both of these devices are breath-actuated, that is, requiring effective positive respiratory effort to inhale medication.

ICS/LABA combination

Inhaled corticosteroid (ICS) therapy is recommended as combination treatment with LABA for patients with a history of frequent acute exacerbations of their COPD. Breo Ellipta, approved in April 2015, combines the new LABA vilanterol with an inhaled corticosteroid already on the market, fluticasone. Vilanterol allows this product to be dosed once daily compared with existing ICS/LABA combination products that are dosed twice daily including Advair Diskus (fluticasone-salmeterol), Symbicort (budesonide-formoterol) and Dulera (mometasone-formoterol).

Long-term ICS treatment is associated with multiple adverse effects including fractures, oral fungal overgrowth and respiratory infections. Therefore, treatment with ICS in patients with COPD should be carefully evaluated when assessing the risk/benefit ratio due to the risk of pneumonia. Their benefit in patients at low risk of exacerbations is questionable1.

Place in hospice therapy

The major disadvantage of these combination therapies for the hospice patient is the method in which the medication is delivered via a metered-dose inhaler or a dry powder inhaler. In patients with advanced disease, who may not have enough positive inhalation, nebulized therapies may be more efficacious than inhalers. Therefore, the combination treatment of short-acting muscarinic antagonist (SAMAs) and short-acting beta 2- adrenergic agonist (SABAs), such as DuoNeb (ipratropium-albuterol) is usually recommended as an alternative. Routine use of DuoNeb should provide an equivalent coverage compared to LAMA/LABA combination products. Although the dosing frequency (four times daily) may be considered as a drawback compared to the long-acting combination products, the short-acting combination therapy may also be used on as-needed basis for acute management of dyspnea in addition to the scheduled dosing. Since the newer combination products are generally cost prohibitive, DuoNeb also serves a cost-effective alternative for hospice patients. In cases where a patient has high risk of exacerbation, a low dose oral corticosteroid may be considered and they are inexpensive compared to inhaled corticosteroids.

 

Cost Comparison Chart.  (costs based on average wholesale pricing)

 

Reference

  1. Magnussen, Disse, Rodriguea-Roisin, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD.
    N. Engl. J. Med. 2014;371:1285-4.

 

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