How Effective Is Cytisine for Smoking Cessation?
How Effective Is Cytisine for Smoking Cessation?
This is Andy Shorr from Washington, DC, with a pulmonary and critical care literature update. I would like to point out an article that was in the September 29 issue of The New England Journal of Medicine by West and colleagues. These authors focused on smoking cessation, an important topic for pulmonologists.
As all of you are aware, tobacco exposure is the leading cause of COPD (chronic obstructive pulmonary disease) and leads to billions of deaths globally each year. For every year that a patient does not quit smoking after his or her mid-30s, life expectancy [is reduced] by about 3 months. Smoking has multiple harmful effects beyond the lung, and you are all aware of what they are. We have a number of options for smoking cessation in the United States, ranging from nicotine replacement to varenicline, and all of them are associated with rather marginal quit rates. However, they are certainly better than placebo. Unfortunately, all of them tend to be expensive.
Of course, the burden of smoking extends beyond just the United States. Tobacco use is a global problem, and the prices that are charged for compounds that are commercially available in the United States could never be afforded outside of the United States. In many cases, they are not necessarily affordable inside the United States, either.
These authors looked at a compound that has been available in parts of Europe called cytisine and decided to do what had never been done for this molecule -- a randomized controlled trial. This drug works at similar receptors that varenicline does, such as those that are responsible for cravings related to nicotine, the nicotinic acetylcholine receptors in the brain. Historically, it was thought that this drug could never really be that effective because it does not cross the blood-brain barrier. However, all of those data about the blood-brain barrier and penetration are from nonhuman studies. These authors went against the weight of those nonhuman studies because they have a lot of observational experience in parts of Europe that suggests that the drug does have some benefit. This is what prompted them to do a double-blind randomized controlled trial.
This was a small study that included only about 1400 patients and it was a single-center study, not a multicenter effort. The study certainly had limitations. The study design was very simple. They [randomly assigned] patients to the molecule or placebo [groups] and followed them over 12 months, with the primary endpoint being quit rates at 12 months. The group of patients was similar to those whom we would have difficulty getting to quit smoking. The population was somewhat older, nearly 50 years of age, and they had tried to quit at least once before. Nearly 80% of patients had tried to quit once before, and many of them had been smoking for more than 30 years. This was a pretty challenging population.
As part of the study design, psychosocial interventions were limited, so there were not a lot of phone calls for support groups. There was no mandatory counseling like you have seen in a lot of studies done in the United States because the authors wanted to reflect the real-world use of the molecule. Then they used standardized measures for assessing abstinence that have been validated in a number of clinical trials. At the end of the study, 12 months later, patients assigned to the molecule had significantly higher quit rates than patients who [received placebo]. Quit rates were about 8.4% in patients assigned to the active drug vs about 2.4% in patients assigned to placebo. When they looked at any effort for abstinence or any period of abstinence during the 12 months, the numbers were higher compared with those for sustained abstinence.
The drug was very well tolerated in terms of safety and its safety profile. There were very few adverse events. The most common adverse events were related to GI (gastrointestinal) symptoms and GI upset, but that very rarely led to drug discontinuation. There was no suggestion of suicidal ideation, which had been related to varenicline. Of course, the study was never powered to look at that because the case reports for varenicline did not emerge until after the drug was commercially available, when its use was much more extensive and in a broader population. However, the authors of this article counter that this drug has been commercially available in parts of Europe for a long time and that suicidal ideation has not been reported, suggesting that this may not be an issue.
A 6% absolute difference in quit rates does not sound impressive, especially when you are starting with quit rates or sustained abstinence rates that are very low, but that is historically what we have seen in other trials of smoking cessation. Remember that this study did not include other types of behavioral counseling or support, which may also explain the lower absolute quit rates and the relative differences. Clearly, there is signal that this molecule was efficacious for the purpose in which it was employed.
This drug is much less expensive than currently available options. I think that what we all need to see are follow-up studies that are multicenter, that enroll broader types of patients, and that look at this molecule head-to-head vs other treatments we have available, perhaps in combination with or in addition to other treatments , whether they are antidepressants such as bupropion or nicotine replacement or varenicline.
Getting our patients to quit smoking is perhaps the hardest thing we face in pulmonary and critical care medicine. It is something that is very challenging and very frustrating, not only for our patients but also for us. However, of all the things we do in clinic, it is certainly the one that is going to reap the biggest health rewards in the future.
I think we are going to be seeing a lot more about this molecule in the next couple of years as broader clinical trials are done and as there might be an effort to bring it to the United States. I want you to be aware of this article because it is putting out there that we can do randomized controlled trials with these types of molecules, hold them to a high standard of evidence, and get some very interesting conclusions. This is Andy Shorr from Washington, DC. Thank you.
This is Andy Shorr from Washington, DC, with a pulmonary and critical care literature update. I would like to point out an article that was in the September 29 issue of The New England Journal of Medicine by West and colleagues. These authors focused on smoking cessation, an important topic for pulmonologists.
As all of you are aware, tobacco exposure is the leading cause of COPD (chronic obstructive pulmonary disease) and leads to billions of deaths globally each year. For every year that a patient does not quit smoking after his or her mid-30s, life expectancy [is reduced] by about 3 months. Smoking has multiple harmful effects beyond the lung, and you are all aware of what they are. We have a number of options for smoking cessation in the United States, ranging from nicotine replacement to varenicline, and all of them are associated with rather marginal quit rates. However, they are certainly better than placebo. Unfortunately, all of them tend to be expensive.
Of course, the burden of smoking extends beyond just the United States. Tobacco use is a global problem, and the prices that are charged for compounds that are commercially available in the United States could never be afforded outside of the United States. In many cases, they are not necessarily affordable inside the United States, either.
These authors looked at a compound that has been available in parts of Europe called cytisine and decided to do what had never been done for this molecule -- a randomized controlled trial. This drug works at similar receptors that varenicline does, such as those that are responsible for cravings related to nicotine, the nicotinic acetylcholine receptors in the brain. Historically, it was thought that this drug could never really be that effective because it does not cross the blood-brain barrier. However, all of those data about the blood-brain barrier and penetration are from nonhuman studies. These authors went against the weight of those nonhuman studies because they have a lot of observational experience in parts of Europe that suggests that the drug does have some benefit. This is what prompted them to do a double-blind randomized controlled trial.
This was a small study that included only about 1400 patients and it was a single-center study, not a multicenter effort. The study certainly had limitations. The study design was very simple. They [randomly assigned] patients to the molecule or placebo [groups] and followed them over 12 months, with the primary endpoint being quit rates at 12 months. The group of patients was similar to those whom we would have difficulty getting to quit smoking. The population was somewhat older, nearly 50 years of age, and they had tried to quit at least once before. Nearly 80% of patients had tried to quit once before, and many of them had been smoking for more than 30 years. This was a pretty challenging population.
As part of the study design, psychosocial interventions were limited, so there were not a lot of phone calls for support groups. There was no mandatory counseling like you have seen in a lot of studies done in the United States because the authors wanted to reflect the real-world use of the molecule. Then they used standardized measures for assessing abstinence that have been validated in a number of clinical trials. At the end of the study, 12 months later, patients assigned to the molecule had significantly higher quit rates than patients who [received placebo]. Quit rates were about 8.4% in patients assigned to the active drug vs about 2.4% in patients assigned to placebo. When they looked at any effort for abstinence or any period of abstinence during the 12 months, the numbers were higher compared with those for sustained abstinence.
The drug was very well tolerated in terms of safety and its safety profile. There were very few adverse events. The most common adverse events were related to GI (gastrointestinal) symptoms and GI upset, but that very rarely led to drug discontinuation. There was no suggestion of suicidal ideation, which had been related to varenicline. Of course, the study was never powered to look at that because the case reports for varenicline did not emerge until after the drug was commercially available, when its use was much more extensive and in a broader population. However, the authors of this article counter that this drug has been commercially available in parts of Europe for a long time and that suicidal ideation has not been reported, suggesting that this may not be an issue.
A 6% absolute difference in quit rates does not sound impressive, especially when you are starting with quit rates or sustained abstinence rates that are very low, but that is historically what we have seen in other trials of smoking cessation. Remember that this study did not include other types of behavioral counseling or support, which may also explain the lower absolute quit rates and the relative differences. Clearly, there is signal that this molecule was efficacious for the purpose in which it was employed.
This drug is much less expensive than currently available options. I think that what we all need to see are follow-up studies that are multicenter, that enroll broader types of patients, and that look at this molecule head-to-head vs other treatments we have available, perhaps in combination with or in addition to other treatments , whether they are antidepressants such as bupropion or nicotine replacement or varenicline.
Getting our patients to quit smoking is perhaps the hardest thing we face in pulmonary and critical care medicine. It is something that is very challenging and very frustrating, not only for our patients but also for us. However, of all the things we do in clinic, it is certainly the one that is going to reap the biggest health rewards in the future.
I think we are going to be seeing a lot more about this molecule in the next couple of years as broader clinical trials are done and as there might be an effort to bring it to the United States. I want you to be aware of this article because it is putting out there that we can do randomized controlled trials with these types of molecules, hold them to a high standard of evidence, and get some very interesting conclusions. This is Andy Shorr from Washington, DC. Thank you.