Tiotropium bromide for Uncontrolled Asthma
Hi, this is Andy Shorr, from the Washington Hospital Center with a Pulmonary and Critical Care literature update. I'd like to talk to you today about an article that was published recently in The New England Journal of Medicine by Peters and colleagues. This article focused on a very unique approach to the patient with uncontrolled asthma. Traditionally, when we find someone who is not well-controlled on moderate-dose inhaled steroids, our approach has been to evaluate either increasing to high-dose corticosteroids or, alternatively, adding a long-acting beta agonist.
For some time, that was not a difficult decision; however, over the past several years, a number of safety issues have arisen about the use of long-acting beta agonists, particularly in patients with asthma, and so efforts have been made to find alternative strategies to the dilemma of exposing the patient to a long-acting beta agonist, or to even higher doses of corticosteroids.
In this study by Peters and colleagues, which was a National Institutes of Health, multicenter, randomized controlled trial, they took patients (n = 210) with uncontrolled asthma, who were on moderate-dose inhaled corticosteroids, and randomly assigned them to 1 of 3 interventions: (1) higher dose corticosteroids; (2) addition of a long-acting beta agonist (in this case, salmeterol); or (3) addition of tiotropium. This represented the novel aspect of the study.
This was a 3-way crossover study, so patients were exposed to each of the 3 arms, and multiple dummies were included in each arm. When they looked at the primary endpoint, which was asthma control and peak flow, and compared the addition of tiotropium arm with the high-dose corticosteroid arm, the investigators found that tiotropium was in fact superior, on the basis of the predefined endpoints. Asthma control days were better with tiotropium than with the higher dose of inhaled steroid, as were peak flow and other measures of asthma disease severity.
When the investigators looked at the comparison of tiotropium added to moderate-dose inhaled corticosteroids, or to salmeterol added to moderate-dose inhaled corticosteroids, they found that, in general, the 2 approaches were equivalent, but for peak flow, which was the only surrogate considered in the study, in terms of asthma control, the use of tiotropium was superior to the use of salmeterol in addition to the moderate-dose inhaled corticosteroid.
This was a very short-term study, without substantial long-term follow-up, so it's unclear what would have happened if these drugs were continued for some period of time, if a tachyphylaxis syndrome might have occurred, if other safety issues might have arisen, but it's certainly a very thought-provoking approach to our patients with asthma. As pulmonologists, poorly controlled patients on moderate-dose inhaled corticosteroids are often referred to us, as are patients with severe asthma who are not controlled at all, and we often struggle with what to do for these patients.
These preliminary data suggest a possible role for a long-acting anticholinergic, such as tiotropium, in patients with asthma. We need larger studies, because, again this study had only 210 patients, and we need longer periods of observation. However, this is quite thought-provoking, in that it may actually create a paradigm shift in our approach to asthma. I'm not advocating the use of tiotropium in the asthmatic population yet -- I think we need better studies, we need more data from follow-up, and we also need better information about biologic plausibility because other studies with anticholinergics have not been so successful in asthma, so we need to see all of those things to "thread the needle." However, this is truly novel, in that it would create a new paradigm on which to focus when it comes to our approach to the patient with moderately severe asthma that isn't adequately controlled on moderate doses of inhaled corticosteroids.
The article was by Peters and colleagues in the October, 2010 issue of The New England Journal of Medicine. This is Andy Shorr from the Washington Hospital Center.
Hi, this is Andy Shorr, from the Washington Hospital Center with a Pulmonary and Critical Care literature update. I'd like to talk to you today about an article that was published recently in The New England Journal of Medicine by Peters and colleagues. This article focused on a very unique approach to the patient with uncontrolled asthma. Traditionally, when we find someone who is not well-controlled on moderate-dose inhaled steroids, our approach has been to evaluate either increasing to high-dose corticosteroids or, alternatively, adding a long-acting beta agonist.
For some time, that was not a difficult decision; however, over the past several years, a number of safety issues have arisen about the use of long-acting beta agonists, particularly in patients with asthma, and so efforts have been made to find alternative strategies to the dilemma of exposing the patient to a long-acting beta agonist, or to even higher doses of corticosteroids.
In this study by Peters and colleagues, which was a National Institutes of Health, multicenter, randomized controlled trial, they took patients (n = 210) with uncontrolled asthma, who were on moderate-dose inhaled corticosteroids, and randomly assigned them to 1 of 3 interventions: (1) higher dose corticosteroids; (2) addition of a long-acting beta agonist (in this case, salmeterol); or (3) addition of tiotropium. This represented the novel aspect of the study.
This was a 3-way crossover study, so patients were exposed to each of the 3 arms, and multiple dummies were included in each arm. When they looked at the primary endpoint, which was asthma control and peak flow, and compared the addition of tiotropium arm with the high-dose corticosteroid arm, the investigators found that tiotropium was in fact superior, on the basis of the predefined endpoints. Asthma control days were better with tiotropium than with the higher dose of inhaled steroid, as were peak flow and other measures of asthma disease severity.
When the investigators looked at the comparison of tiotropium added to moderate-dose inhaled corticosteroids, or to salmeterol added to moderate-dose inhaled corticosteroids, they found that, in general, the 2 approaches were equivalent, but for peak flow, which was the only surrogate considered in the study, in terms of asthma control, the use of tiotropium was superior to the use of salmeterol in addition to the moderate-dose inhaled corticosteroid.
This was a very short-term study, without substantial long-term follow-up, so it's unclear what would have happened if these drugs were continued for some period of time, if a tachyphylaxis syndrome might have occurred, if other safety issues might have arisen, but it's certainly a very thought-provoking approach to our patients with asthma. As pulmonologists, poorly controlled patients on moderate-dose inhaled corticosteroids are often referred to us, as are patients with severe asthma who are not controlled at all, and we often struggle with what to do for these patients.
These preliminary data suggest a possible role for a long-acting anticholinergic, such as tiotropium, in patients with asthma. We need larger studies, because, again this study had only 210 patients, and we need longer periods of observation. However, this is quite thought-provoking, in that it may actually create a paradigm shift in our approach to asthma. I'm not advocating the use of tiotropium in the asthmatic population yet -- I think we need better studies, we need more data from follow-up, and we also need better information about biologic plausibility because other studies with anticholinergics have not been so successful in asthma, so we need to see all of those things to "thread the needle." However, this is truly novel, in that it would create a new paradigm on which to focus when it comes to our approach to the patient with moderately severe asthma that isn't adequately controlled on moderate doses of inhaled corticosteroids.
The article was by Peters and colleagues in the October, 2010 issue of The New England Journal of Medicine. This is Andy Shorr from the Washington Hospital Center.
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