Pulmonary Q&A: More Treatment Choices for Patients With COPD

July 2, 2004

Several new drugs are being introduced-and more are on thehorizon.

Q:What are the newer optionsfor patients with chronicobstructive pulmonary disease(COPD)?

A: Several new drugs are being introduced--and more are on thehorizon.

Tiotropium. This long-acting anticholinergicbronchodilator, introducedearlier in Europe and elsewhere,is now approved for long-term,once-daily maintenance treatment ofCOPD in the United States. Tiotropiumis delivered as a dry powder via adevice known as the HandiHaler. It offersseveral advantages over the establishedanticholinergic, ipratropium,which is used extensively as a firstlineshort-acting bronchodilator forsymptomatic relief. Tiotropium binds to M3 muscarinic receptors responsiblefor bronchodilatation more firmly and for a longer time than ipratropium.1,2 Theduration of action of tiotropium is 24 hours or more, which makes it suitable foronce-daily dosing.3 By comparison, ipratropium is usually administered 4 to 6times per day. Recent controlled clinical trials show that tiotropium is superiorto ipratropium for long-term bronchodilation and symptomatic improvement.3,4

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

Tiotropium offers sustained bronchodilation that exceeds that producedby the 2 long-acting β-agonists salmeterol and formoterol. When tested againstsalmeterol, tiotropium was more potent and longer-lasting.5,6 No studies havethus far evaluated the effectiveness of tiotropium combined with a long-actingβ-agonist.

Tiotropium may well become a “cornerstone drug” in the maintenancemanagement of symptomatic stages of COPD. Unlike other widely used bronchodilators,tiotropium appears to elevate baseline lung function, as measuredby 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 thisclinical setting.

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

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

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