More Treatment Choices for Patients With COPD

Q: What are the newer options for patients with chronic obstructive pulmonary disease (COPD)?

A: Several new drugs are being introduced— and more are on the horizon.

Tiotropium. This long-acting anticholinergic bronchodilator, introduced earlier in Europe and elsewhere, is now approved for long-term, once-daily maintenance treatment of COPD in the United States. Tiotropium is delivered as a dry powder via a device known as the HandiHaler. It offers several advantages over the established anticholinergic, ipratropium, which is used extensively as a firstline short-acting bronchodilator for symptomatic relief. Tiotropium binds to M₃ muscarinic receptors responsible for bronchodilatation more firmly and for a longer time than ipratropium.^1,2 The duration of action of tiotropium is 24 hours or more, which makes it suitable for once-daily dosing.³ By comparison, ipratropium is usually administered 4 to 6 times per day. Recent controlled clinical trials show that tiotropium is superior to ipratropium for long-term bronchodilation and symptomatic improvement.^3,4

Ipratropium and albuterol have also been available for some time in a combination aerosol bronchodilator that is used 3 or 4 times a day for symptomatic relief.

Tiotropium offers sustained bronchodilation that exceeds that produced by the 2 long-acting β-agonists salmeterol and formoterol. When tested against salmeterol, tiotropium was more potent and longer-lasting.^5,6 No studies have thus far evaluated the effectiveness of tiotropium combined with a long-acting β-agonist.

Tiotropium may well become a “cornerstone drug” in the maintenance management of symptomatic stages of COPD. Unlike other widely used bronchodilators, tiotropium appears to elevate baseline lung function, as measured by forced expiratory volume in 1 second (FEV₁) over time.⁷ It may thus be useful in early stages of COPD, although it has not yet been evaluated in this clinical setting.

Fluticasone/salmeterol. The combination of fluticasone and salmeterol, which is delivered in a dry-powder inhaler (Diskus), was approved by the FDA as maintenance therapy for patients with COPD.^8,9 Although the role of inhaled corticosteroids remains controversial in moderate to severe COPD, their use is increasing.¹⁰ The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations specify that long-term use of inhaled and oral corticosteroids be reserved for patients who have a documented spirometric response to corticosteroids and those who have an FEV₁ of less than 50% of predicted and repeated exacerbations that require treatment with antibiotics and oral corticosteroids.¹¹

Future options. Drugs on the horizon include the phosphodiesterase-4 inhibitors, 2 of which—cilomilast and roflumilast—are in phase 3 clinical trials. Roflumilast is currently awaiting regulatory approval in Europe for the management of asthma and COPD. Results of early clinical trials appear to show that this agent, taken once daily, improves FEV₁ significantly more than placebo and reduces the number of COPD exacerbations in a dose-dependent manner. ¹² Other drugs, such as mucotropic agents, are being investigated.¹³