Mary Ann Moon

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

For patients newly diagnosed with ulcerative colitis and receiving their first systemic corticosteroids, their endoscopic response to treatment is a better predictor of future clinical course than is their clinical response, Dr. Sandro Ardizzone and his colleagues reported in the June issue of Clinical Gastroenterology and Hepatology.

In a study of 157 such patients, those who improved clinically but did not show a complete endoscopic response after 3 months of therapy had a much higher rate of negative outcomes (49%) during the ensuing 5 years than did patients who initially showed both clinical improvement and a complete endoscopic response (27%).

For this reason, clinical assessment of treatment response may not be sufficient for many patients. Instead, the degree of mucosal healing seen on endoscopy should be used to predict outcomes such as the patient’s needs for hospitalization, immunosuppressants, and even colectomy in the near future, said Dr. Ardizzone, head of the inflammatory bowel disease unit and chair of gastroenterology at "L. Sacco" University Hospital, Milan, and his associates.

Few studies have evaluated the role of mucosal healing in relation to long-term disease outcomes, and some of the studies were poorly designed in that they had heterogeneous patient populations, treatments, and durations of follow-up. Dr. Ardizzone and his colleagues performed a chart review of 157 patients seen at their hospital, a tertiary-care IBD center, between 1981 and 2006 (Clin. Gastroenterol. Hepatol. 2011 June [doi:10.1016/j.cgh.2010.12.028]).

All the study subjects had newly diagnosed moderate to severe ulcerative colitis and presented as emergencies, needing their first systemic corticosteroid treatment. They were given either oral prednisone or parenteral methylprednisolone, which was tapered over a standard period of 3 months.

A total of 68% of the subjects were men, and 12% had a family history of IBD. The median age was 34 years (range, 23-48 years). All the patients were assessed at 3 and 6 months, then at 6-month intervals for up to 5 years, or until they underwent colectomy.

Within 1 year, 65% of patients had at least one relapse, 30% required hospitalization for ulcerative colitis, 19% required immunosuppressants, and 5% required colectomy.

Within 5 years, 92% relapsed, including 38% with multiple systemic relapses. In addition, 73% required at least one new course of systemic corticosteroids; 45% required hospitalization; 28% required immunosuppressants; and 12% required colectomy.

A total of 63% of patients achieved clinical remission at 3 months, which was defined as a score of 0-1 on a modified Powell-Tuck index of clinical signs and symptoms. However, less than half of them – 38% of the entire study population – achieved endoscopic remission at 3 months, which was defined as a score of 0 on a modified Baron scale of erythema, edema, granularity, bleeding in response to touch, spontaneous bleeding, erosion, or ulceration of the gastrointestinal mucosa.

Early (3-month) treatment response on endoscopy was the only factor that correlated with the primary combined end point of need for immunosuppressants, hospitalization, and colectomy. Failure to achieve complete remission on endoscopy after the first course of steroids predicted a more aggressive course of disease.

"Our data clearly show that despite clinical improvement, endoscopic nonresponders have a significantly higher rate of combined negative end points (49%) than complete responders (27%)," the researchers said.

This suggests that physicians might want to consider ordering routine endoscopic monitoring after the initial course of corticosteroid therapy.

The study findings further suggest that in patients who do not achieve complete endoscopic healing at that time, the early introduction of more aggressive treatments, such as immunosuppressants, may be warranted. However, "this approach requires validation in prospective trials," the investigators noted.

Dr. Ardizzone and his associates are now conducting a randomized, controlled trial to determine whether such monitoring and intervention improve patient outcomes.

One of Dr. Ardizzone’s associates was supported by Fondazione Romeo ed Enrica Invernizzi. No other conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Use of aspirin and NSAIDs raises the risk for both diverticulitis and diverticular bleeding, Dr. Lisa L. Strate and her colleagues reported in the May issue of Gastroenterology.

"These findings have important clinical and public health implications, given the prevalence of diverticular disease and NSAID use, particularly in the elderly," said Dr. Strate of the University of Washington and Harborview Medical Center, Seattle, and her associates from Harvard Medical School and Harvard School of Public Health.

Photo credit: ©jimdeli/Fotolia.com

Previous case-control studies and one cohort study have reported similar associations, but have focused on very severe disease or have combined the findings on diverticulitis and diverticular bleeding. Differentiating between the two is crucial because they likely have distinct biological mechanisms, the researchers said.

Previous studies also have neither been large enough nor have had extensive enough follow-up to tease out the specific effects of dosage, frequency, duration, and timing of medication use in relation to diverticular complications, as well as to account for important confounders such as diet, body mass index, and physical activity level.

To address these issues, Dr. Strate and her colleagues analyzed data from the Health Professionals Follow-Up Study, a cohort of more than 47,210 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists in the United States who were aged 40-75 years at baseline in 1986 and have been followed biennially for 22 years. The data include detailed information on diet, medication use, and diverticular symptoms and treatments.

A total of 29% of the participants reported regular aspirin use (defined as two or more times per week), and 5% reported regular NSAID use. The participants said they used aspirin to treat existing cardiovascular disease (25%), to prevent CVD (58%), to treat headaches (25%), to treat joint or musculoskeletal pain (33%), or for other reasons (7%).

There were 939 incident cases of diverticulitis and 256 incident cases of diverticular bleeding during 859,164 person-years of follow-up.

Compared with men who did not use aspirin or NSAIDs regularly, those who did showed a significantly higher risk of developing diverticulitis (hazard ratio, 1.25 for aspirin and 1.72 for NSAIDs). The associations were similar for diverticular bleeding (HR, 1.70 for aspirin and 1.74 for NSAIDs).

NSAIDs were more strongly associated with complicated diverticulitis than with uncomplicated diverticulitis, whereas aspirin was equally associated with both subtypes of diverticulitis.

"The highest risk of diverticular bleeding was observed in men who used aspirin with moderately high frequency [defined as 4-6 days per week] and in moderately high doses [defined as two to six standard tablets per week]. For diverticulitis, the risk appeared somewhat greater for regular NSAID users than for regular aspirin users, and the risk increased with frequency of aspirin use but not with higher doses," the investigators said.

"To address the possibility of confounding by comorbid illness, we additionally adjusted our analyses for CVD and osteoarthritis, the two most common indications for aspirin use in this cohort. In this analysis, the relationships between aspirin/NSAID use and diverticulitis remained largely unchanged."

"For diverticular bleeding, the association with aspirin use was not materially altered, but the association with NSAIDs was somewhat attenuated," they said.

"There are several possible mechanisms by which aspirin and NSAIDs might promote diverticular complications," the researchers added.

Both medications are thought to damage the colon directly by topical injury, and to do so indirectly by impairing prostaglandin synthesis, which in turn compromises mucosal integrity and increases mucosal permeability, allowing the influx of bacteria and other toxins.

Both also are likely to promote blood loss from mucosal lesions by inhibiting platelet aggregation.

This study was limited in that it involved only well-educated men, so the results may not be generalizable to other populations.

In conclusion, given the significantly elevated risks of diverticulitis and diverticular bleeding in users of aspirin or NSAIDs, analgesic medications should be selected carefully in patients known to have these disorders, particularly in those who have already had complications, Dr. Strate and her associates said.

This study was supported by the National Institutes of Health. Two of the authors received support from the Damon Runyon Cancer Research Foundation and the American Gastroenterological Association, respectively. No conflicts of interest were reported.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Two "pragmatic" studies of leukotriene receptor antagonists in real-world asthma patients fell just short of demonstrating the drugs’ equivalence with inhaled glucocorticoids as first-line therapy and with beta-agonists as add-on therapy for exacerbations, according to a report in the May 5 issue of the New England Journal of Medicine.

Leukotriene receptor antagonists (LTRAs) met the criteria for equivalence to the other medications at 2-month follow-up, a time point that "represents a standard efficacy period" in most clinical trials. But LTRAs fell just shy of meeting the criteria for equivalence at 2-year follow-up, and that was the primary outcome measure for both studies, said Dr. David Price of the University of Aberdeen (Scotland) and his associates.

Despite this negative finding, "our [results] suggest that there is little difference in real-world effectiveness between an LTRA and an inhaled glucocorticoid as first-line controller therapy and between an LTRA and a long-acting beta-agonist as an add-on to an inhaled glucocorticoid," they said.

"Caution is needed in interpreting the results of these pragmatic trials," they noted.

In a perspective piece accompanying Dr. Price’s report, James H. Ware, Ph.D., and Dr. Mary Beth Hamel agreed, citing the "many challenges" involved in conducting pragmatic trials and interpreting their findings (N. Engl. J. Med. 2011;364:1685-7).

But "despite the trials’ limitations, the data provide encouraging evidence of equivalence or near-equivalence of the treatment strategies over the course of 2 years. Though imperfect, they provide helpful guidance for clinical care," said Dr. Ware, professor of biostatistics at Harvard School of Public Health, Boston, and a statistical consultant to the New England Journal of Medicine, and Dr. Hamel, also of Harvard and a deputy editor of the journal.

The two studies, conducted in parallel at 53 primary care practices throughout the United Kingdom, were funded primarily by the U.K. Health Technology Assessment Programme "for the explicit purpose of informing guidelines for asthma management in the British National Health Service," Dr. Ware and Dr. Hamel noted.

Both studies were unblinded and sought to enroll a broad spectrum of asthma patients aged 12-80 years, so as to reflect the complexity and diversity of routine clinical practice. However, because the studies ended up with very few subjects younger than 25 years of age, "our findings apply only to adults," Dr. Price and his colleagues said.

In the first study, 306 patients were randomly assigned to open-label treatment with either an LTRA (montelukast or zafirlukast) or an inhaled glucocorticoid (beclomethasone, budesonide, or fluticasone) as first-line therapy. Mean scores on the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) were equivalent between the two groups at 2 months, as were secondary end points of the frequency of exacerbations and mean scores on the Asthma Control Questionnaire, the Royal College of Physicians three-item questionnaire (RCP3), and the Mini Rhinoconjunctivitis Quality of Life Questionnaire.

All these secondary end points also were equivalent at 2-year follow-up. But mean scores on the MiniAQLQ did not meet the prespecified criteria for equivalence at 2 years.

In the second study, 352 patients whose asthma was not well controlled with inhaled glucocorticoids were randomly assigned to open-label add-on treatment with either an LTRA or a long-acting beta-agonist. Again, mean scores on the MiniAQLQ demonstrated equivalence of the two medications at 2 months, as did all the secondary end points at both 2 months and 2 years.

But again, the primary end point of mean scores on the MiniAQLQ at 2 years fell just outside the prespecified criteria for equivalence.

These results "suggest that an LTRA is equivalent to both comparison drugs with regard to the effect on asthma-related quality of life at 2 months in a diverse patient population with asthma," the investigators said (N. Engl. J. Med. 2011;364:1695-707).

However, they also "suggest that caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."

In both of these trials, leukotriene receptor antagonists were "essentially equivalent" in efficacy – findings that challenge current guidelines that favor inhaled glucocorticoids, according to Dr. Sven-Erik Dahlen and Dr. Barbro Dahlen of the Karolinska Institutet, Stockholm, and Dr. Jeffrey M. Drazen, editor in chief of the New England Journal of Medicine.

"The data reported by Price et al. send an important message to both the family doctor and the hospital specialist," they said in an editorial (N. Engl. J. Med. 2011;364:1769-70) accompanying Dr. Price’s report.

"Oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do."

They added, "We think this alternative approach works in the real-world setting primarily because it is easier to take a pill once or twice a day than to use an inhaler. The data from the two studies support this view, since the rates of adherence to the oral LTRAs were 65% and 74% in the first-line controller and add-on therapy trials, respectively, compared with only 41% and 46% for the inhaled glucocorticoid."

This study was supported primarily by the U.K. Health Technology Assessment Programme. Additional funding for the study was provided by Clement Clarke International, Merck Sharp & Dohme, AstraZeneca, and Research in Real Life. Dr. Price and his associates reported numerous ties to industry sources. Dr. Ware and Dr. Hamel reported no conflicts of interest. Dr. Sven-Erik Dahlen reported ties to Regeneron Pharmaceuticals and GlaxoSmithKline, and Dr. Barbro Dahlen reported ties to Actelion and Genentech.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.

Among men who undergo radical prostatectomy for early prostate cancer, "there continues to be a significant reduction in the rate of death from any cause, the rate of death from prostate cancer, and the risk of metastases" 15 years after surgery, compared with "watchful waiting," according to a report in the May 5 issue of the New England Journal of Medicine.

The benefit of radical prostatectomy is even seen in men with low-risk tumors. "Our findings show that some tumors that are considered to be low risk at diagnosis do pose a threat to life, especially if they are not surgically removed," said Dr. Anna Bill-Axelson of University Hospital, Uppsala, Sweden, and her associates.

The researchers previously reported their findings from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after 9 years of follow-up, and now report estimated results at the 15-year mark in a population followed for a median of 12.8 years.

The study subjects were 695 men in Sweden, Finland, and Iceland who had newly diagnosed localized prostate cancer in 1989-1999, and were randomly assigned to either radical prostatectomy (347 patients) or watchful waiting (348 patients). The tumors were moderately well differentiated to well differentiated, and bone scan results were negative at baseline.

The subjects’ mean age at baseline was 65 years, and their mean prostate-specific antigen level was approximately 13 ng/mL.

At long-term follow-up, 55 men in the prostatectomy group and 81 in the watchful waiting group had died of prostate cancer. The cumulative incidence of death at 15 years was significantly lower – 15% – with surgery than with watchful waiting (21%). This corresponds to a relative risk of death in the radical prostatectomy group of 0.62.

Similarly, the cumulative incidence of distant metastases was significantly lower, at 22%, in the radical prostatectomy group, compared with 33% in the watchful waiting group. And the cumulative incidence of local progression was significantly lower, at 22%, with surgery, compared with 49% in the watchful waiting group.

The benefit with radical prostatectomy persisted across several subgroups. It was consistent regardless of Gleason score and prostate-specific antigen level at diagnosis. Surprisingly, even men with low-risk tumors showed rates of death due to prostate cancer and of metastases that were similar to rates in the entire study cohort, she said.

These findings "contradict the notion that there is only a distinct subpopulation that responds to radical surgery with an early reduction in risk," Dr. Bill-Axelson and her colleagues said (N. Engl. J. Med. 2011;364:1708-17).

The mortality and disease progression benefits were "obvious" among men younger than 65 years of age, "but it is still unclear whether the benefit extends to older men." In the overall cohort, the number needed to treat with radical surgery to avert one death was 15, but it was only 7 among men younger than 65.

In this study, "the apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," the investigators noted.

One other subgroup of patients – those found to have extracapsular tumor growth on histopathologic analysis – had poor outcomes regardless of treatment assignment. "The risk of death from prostate cancer after radical prostatectomy among men who had tumors with extracapsular growth, as compared with men who had tumors without extracapsular growth, was increased by a factor of 7," they said.

"Although extracapsular growth is not a perfect predictor of lethal disease, our findings indicate that these men could be a group for which adjuvant local or systemic therapy would be beneficial," the investigators added.

"With continued follow-up, data from the SPCG-4 study may allow us to identify prognostic markers in men assigned to watchful waiting that can serve as trigger points for active treatment." Dr. Bill-Axelson and her associates wrote.

This study was supported by the Swedish Cancer Society and the National Institutes of Health. One coauthor reported ties to Pfizer and Astellas.