Sharon Worcester

Major Finding: Ten factors that were found to be associated with stroke risk were self-reported hypertension, current smoking, abdominal obesity, diet, regular physical activity, diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1.

Data Source: Phase I of INTERSTROKE, a large, multinational, case-control study of 3,000 patients and 3,000 controls.

Disclosures: This study was funded with unrestricted grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Networks, Pfizer Cardiovascular Award, Merck & Co., AstraZeneca, and Boehringer Ingelheim. Multiple authors reported receiving grant/research support, honoraria, expenses, and/or fees from numerous pharmaceutical companies (including those also listed as funding sources for this study), and from other sources, and/or being associated with the American Heart Association as a board member and officer.

Ten distinct risk factors account for about 90% of global stroke risk, according to findings from the first phase of INTERSTROKE, a multinational, case-control study that has enrolled 6,000 patients and controls thus far.

The findings, which suggest that the stroke burden could be substantially reduced by targeted interventions to address the identified risk factors, were published online in the Lancet, and were reported simultaneously at the World Congress of Cardiology in Beijing.

Five of the risk factors that were found to be significantly associated with stroke risk accounted for about 80% of the population-attributable risk for all stroke; these were self-reported hypertension, current smoking, abdominal obesity (highest vs. lowest tertile of waist:hip ratio), diet (highest vs. lowest diet risk score), and regular physical activity. These comparisons yielded odds ratios of 2.64, 2.09, 1.65, 1.35, and 0.69, respectively.

The addition of another five significant risk factors that were identified in this study further increased the population-attributable risk for all stroke associated with these risk factors to 90%. These additional risk factors (diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1) generally increased the odds of stroke by a smaller amount than did the other five risk factors that accounted for a greater proportion of the population-attributable risk. The comparisons yielded odds ratios of 1.36, 1.51, 1.30/1.35, 2.38, and 1.89, respectively.

All risk factors identified in this study were significantly associated with ischemic stroke, whereas hypertension, smoking, waist:hip ratio, diet, and alcohol intake also were significantly associated with intracerebral hemorrhagic stroke, Dr. Martin J. O'Donnell of McMaster University, Hamilton, Ont., and his colleagues reported (Lancet 2010 June 18 [doi:10.1016/S0140-6736(10)60834-3

In an effort to establish the association of conventional and emerging risk factors with stroke, the INTERSTROKE researchers set out to perform a study similar to the INTERHEART study published in 2004, which identified nine modifiable risk factors that explained the majority of myocardial infarctions worldwide.

Between March 1, 2007, and April 23, 2010, the investigators studied 3,000 patients from 22 countries, and 3,000 sex- and age-matched controls with no stroke history. Case patients (2,337 with ischemic stroke and 663 with intracerebral hemorrhagic stroke) presented with acute first stroke, and were enrolled within 5 days of symptom onset and 72 hours of hospital admission. A structured questionnaire and physical examination, including routine neuroimaging, were performed in all patients.

“Our study provides essential information on the importance of common, potentially modifiable vascular risk factors, and builds on previous epidemiological studies,” they wrote, noting that although the risk factors are similar to those identified as being associated with MI in INTERHEART, hypertension, apolipoproteins, physical activity, and alcohol intake appear to have different relative importance for stroke vs. myocardial infarction.

“These findings are important to help guide optimum selection of risk-factor targets for population-based programs to prevent all cardiovascular diseases,” they concluded.

View on the news

Data May Spur Prevention Strategies

Stroke is the second-leading cause of death globally, and the cause of more than 85% of deaths in developing countries. Therefore, research on risk factors for stroke around the world is imperative for addressing the problem.

The INTERSTROKE investigators confirmed that hypertension is the leading risk factor for stroke not only in high-income countries, but also in developing countries.

This finding is especially relevant because it highlights the need for regional health authorities to develop strategies to screen the general population for high blood pressure and offer affordable treatment to reduce the burden of stroke.

The INTERSTROKE study – although limited by its matched case-control design vs. a prospective cohort approach – nonetheless represents an efficient approach to obtaining useful information about stroke risk. The important findings of this study should help inform worldwide stroke prevention strategies and reduce the global burden of stroke.

JACK V. TU, M.D., is with the Institute for Clinical Evaluative Sciences, the Sunnybrook Health Sciences Centre, and the University of Toronto. His comments were originally published in the Lancet (2010 June 18 [

doi:10.1016/S0140-6736(10)60975-0

Major Finding: Ten factors that were found to be associated with stroke risk were self-reported hypertension, current smoking, abdominal obesity, diet, regular physical activity, diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1.

Data Source: Phase I of INTERSTROKE, a large, multinational, case-control study of 3,000 patients and 3,000 controls.

Disclosures: This study was funded with unrestricted grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Networks, Pfizer Cardiovascular Award, Merck & Co., AstraZeneca, and Boehringer Ingelheim. Multiple authors reported receiving grant/research support, honoraria, expenses, and/or fees from numerous pharmaceutical companies (including those also listed as funding sources for this study), and from other sources, and/or being associated with the American Heart Association as a board member and officer.

Ten distinct risk factors account for about 90% of global stroke risk, according to findings from the first phase of INTERSTROKE, a multinational, case-control study that has enrolled 6,000 patients and controls thus far.

The findings, which suggest that the stroke burden could be substantially reduced by targeted interventions to address the identified risk factors, were published online in the Lancet, and were reported simultaneously at the World Congress of Cardiology in Beijing.

Five of the risk factors that were found to be significantly associated with stroke risk accounted for about 80% of the population-attributable risk for all stroke; these were self-reported hypertension, current smoking, abdominal obesity (highest vs. lowest tertile of waist:hip ratio), diet (highest vs. lowest diet risk score), and regular physical activity. These comparisons yielded odds ratios of 2.64, 2.09, 1.65, 1.35, and 0.69, respectively.

The addition of another five significant risk factors that were identified in this study further increased the population-attributable risk for all stroke associated with these risk factors to 90%. These additional risk factors (diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1) generally increased the odds of stroke by a smaller amount than did the other five risk factors that accounted for a greater proportion of the population-attributable risk. The comparisons yielded odds ratios of 1.36, 1.51, 1.30/1.35, 2.38, and 1.89, respectively.

All risk factors identified in this study were significantly associated with ischemic stroke, whereas hypertension, smoking, waist:hip ratio, diet, and alcohol intake also were significantly associated with intracerebral hemorrhagic stroke, Dr. Martin J. O'Donnell of McMaster University, Hamilton, Ont., and his colleagues reported (Lancet 2010 June 18 [doi:10.1016/S0140-6736(10)60834-3

In an effort to establish the association of conventional and emerging risk factors with stroke, the INTERSTROKE researchers set out to perform a study similar to the INTERHEART study published in 2004, which identified nine modifiable risk factors that explained the majority of myocardial infarctions worldwide.

Between March 1, 2007, and April 23, 2010, the investigators studied 3,000 patients from 22 countries, and 3,000 sex- and age-matched controls with no stroke history. Case patients (2,337 with ischemic stroke and 663 with intracerebral hemorrhagic stroke) presented with acute first stroke, and were enrolled within 5 days of symptom onset and 72 hours of hospital admission. A structured questionnaire and physical examination, including routine neuroimaging, were performed in all patients.

“Our study provides essential information on the importance of common, potentially modifiable vascular risk factors, and builds on previous epidemiological studies,” they wrote, noting that although the risk factors are similar to those identified as being associated with MI in INTERHEART, hypertension, apolipoproteins, physical activity, and alcohol intake appear to have different relative importance for stroke vs. myocardial infarction.

“These findings are important to help guide optimum selection of risk-factor targets for population-based programs to prevent all cardiovascular diseases,” they concluded.

View on the news

Data May Spur Prevention Strategies

Stroke is the second-leading cause of death globally, and the cause of more than 85% of deaths in developing countries. Therefore, research on risk factors for stroke around the world is imperative for addressing the problem.

The INTERSTROKE investigators confirmed that hypertension is the leading risk factor for stroke not only in high-income countries, but also in developing countries.

This finding is especially relevant because it highlights the need for regional health authorities to develop strategies to screen the general population for high blood pressure and offer affordable treatment to reduce the burden of stroke.

The INTERSTROKE study – although limited by its matched case-control design vs. a prospective cohort approach – nonetheless represents an efficient approach to obtaining useful information about stroke risk. The important findings of this study should help inform worldwide stroke prevention strategies and reduce the global burden of stroke.

JACK V. TU, M.D., is with the Institute for Clinical Evaluative Sciences, the Sunnybrook Health Sciences Centre, and the University of Toronto. His comments were originally published in the Lancet (2010 June 18 [

doi:10.1016/S0140-6736(10)60975-0

Major Finding: Ten factors that were found to be associated with stroke risk were self-reported hypertension, current smoking, abdominal obesity, diet, regular physical activity, diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1.

Data Source: Phase I of INTERSTROKE, a large, multinational, case-control study of 3,000 patients and 3,000 controls.

Disclosures: This study was funded with unrestricted grants from the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Networks, Pfizer Cardiovascular Award, Merck & Co., AstraZeneca, and Boehringer Ingelheim. Multiple authors reported receiving grant/research support, honoraria, expenses, and/or fees from numerous pharmaceutical companies (including those also listed as funding sources for this study), and from other sources, and/or being associated with the American Heart Association as a board member and officer.

Ten distinct risk factors account for about 90% of global stroke risk, according to findings from the first phase of INTERSTROKE, a multinational, case-control study that has enrolled 6,000 patients and controls thus far.

The findings, which suggest that the stroke burden could be substantially reduced by targeted interventions to address the identified risk factors, were published online in the Lancet, and were reported simultaneously at the World Congress of Cardiology in Beijing.

Five of the risk factors that were found to be significantly associated with stroke risk accounted for about 80% of the population-attributable risk for all stroke; these were self-reported hypertension, current smoking, abdominal obesity (highest vs. lowest tertile of waist:hip ratio), diet (highest vs. lowest diet risk score), and regular physical activity. These comparisons yielded odds ratios of 2.64, 2.09, 1.65, 1.35, and 0.69, respectively.

The addition of another five significant risk factors that were identified in this study further increased the population-attributable risk for all stroke associated with these risk factors to 90%. These additional risk factors (diabetes, alcohol intake of more than 30 drinks per month/binge drinking, psychosocial stress/depression, cardiac causes, and highest vs. lowest tertile of the ratio of apolipoproteins B to A1) generally increased the odds of stroke by a smaller amount than did the other five risk factors that accounted for a greater proportion of the population-attributable risk. The comparisons yielded odds ratios of 1.36, 1.51, 1.30/1.35, 2.38, and 1.89, respectively.

All risk factors identified in this study were significantly associated with ischemic stroke, whereas hypertension, smoking, waist:hip ratio, diet, and alcohol intake also were significantly associated with intracerebral hemorrhagic stroke, Dr. Martin J. O'Donnell of McMaster University, Hamilton, Ont., and his colleagues reported (Lancet 2010 June 18 [doi:10.1016/S0140-6736(10)60834-3

In an effort to establish the association of conventional and emerging risk factors with stroke, the INTERSTROKE researchers set out to perform a study similar to the INTERHEART study published in 2004, which identified nine modifiable risk factors that explained the majority of myocardial infarctions worldwide.

Between March 1, 2007, and April 23, 2010, the investigators studied 3,000 patients from 22 countries, and 3,000 sex- and age-matched controls with no stroke history. Case patients (2,337 with ischemic stroke and 663 with intracerebral hemorrhagic stroke) presented with acute first stroke, and were enrolled within 5 days of symptom onset and 72 hours of hospital admission. A structured questionnaire and physical examination, including routine neuroimaging, were performed in all patients.

“Our study provides essential information on the importance of common, potentially modifiable vascular risk factors, and builds on previous epidemiological studies,” they wrote, noting that although the risk factors are similar to those identified as being associated with MI in INTERHEART, hypertension, apolipoproteins, physical activity, and alcohol intake appear to have different relative importance for stroke vs. myocardial infarction.

“These findings are important to help guide optimum selection of risk-factor targets for population-based programs to prevent all cardiovascular diseases,” they concluded.

View on the news

Data May Spur Prevention Strategies

Stroke is the second-leading cause of death globally, and the cause of more than 85% of deaths in developing countries. Therefore, research on risk factors for stroke around the world is imperative for addressing the problem.

The INTERSTROKE investigators confirmed that hypertension is the leading risk factor for stroke not only in high-income countries, but also in developing countries.

This finding is especially relevant because it highlights the need for regional health authorities to develop strategies to screen the general population for high blood pressure and offer affordable treatment to reduce the burden of stroke.

The INTERSTROKE study – although limited by its matched case-control design vs. a prospective cohort approach – nonetheless represents an efficient approach to obtaining useful information about stroke risk. The important findings of this study should help inform worldwide stroke prevention strategies and reduce the global burden of stroke.

JACK V. TU, M.D., is with the Institute for Clinical Evaluative Sciences, the Sunnybrook Health Sciences Centre, and the University of Toronto. His comments were originally published in the Lancet (2010 June 18 [

doi:10.1016/S0140-6736(10)60975-0

Major Finding: Women had significantly higher mean scores than men on the specific measure of “drive for thinness” (mean of 4.3 vs. 1.8 and 4.0 vs. 2.2 for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean of 10.2 vs. 5.0 and 10.9 vs. 5.5 for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

Data Source: An analysis of data from a clinical trial examining a combined pharmacologic and behavioral intervention for smoking cessation.

Disclosures: The main investigator reported that neither she nor her colleagues had relevant conflicts to disclose.

General and smoking-specific weight concerns were more common among white women than among white men and black men and women preparing to quit smoking, but weight concerns were prevalent in all of the groups, according to a study of 301 individuals enrolled in the Chicago STOP Smoking trial.

For example, black women had the highest scores for “body dissatisfaction,” and their scores in regard to smoking-specific weight concerns were statistically similar to those of white women. Men also had substantial smoking-specific weight concerns, which were defined as the belief that smoking can be used for weight control and that quitting smoking leads to weight gain, Lisa A.P. Sánchez-Johnsen, Ph.D., and her colleagues in the department of psychiatry and behavioral neuroscience at the University of Chicago reported online in Addictive Behaviors.

The findings, some of which contradict conventional wisdom about cultural differences in weight and body image between black and white adults, suggest that both groups have specific concerns about weight and body image that could be important in the development of smoking-cessation programs, the investigators said.

Participants were 73 black women, 46 black men, 90 white women, and 92 white men. Overall, general weight concerns (defined by summated scores on the drive for thinness and body dissatisfaction subscales of the Eating Disorders Inventory–2, and the restraint factor of the Three-Factor Eating Questionnaire) were more common in white vs. black participants, and female vs. male participants, but no race by sex interactions were found, the investigators reported (Addict. Behav. 2010 Aug. 6 [doi:10.1016/j.addbeh.2010.08.001

Women had significantly higher mean scores (after controlling for age, body mass index, socioeconomic status, and cigarettes smoked per day) than did men on the specific measure of “drive for thinness” (mean, 4.3 vs. 1.8 and 4.0 vs. 2.2 on a 1-6 scale for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean, 10.2 vs. 5.0 and 10.9 vs. 5.5 on a 0-21 scale for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

White women did, however, have significantly higher scores on the measure of “cognitive restraint,” which refers to the degree to which people consciously monitor and control their food intake (9.5 vs. 5.6, 6.7, and 5.4 on a 0-21 scale for white men, black women, and black men, respectively). This measure might include a cognitive and behavioral component, unlike other dimensions of weight concerns measured in the study, the investigators reported.

Smoking-specific weight concerns also were highest in white women, but the differences were significant only between white women and white and black men (respective scores, 7.7, 6.0, and 6.3). Black women had substantial smoking-specific weight concerns (score, 6.8).

The findings could be key to the development of smoking-cessation programs that address weight concerns for black and white men and women, the researchers concluded.

Major Finding: Women had significantly higher mean scores than men on the specific measure of “drive for thinness” (mean of 4.3 vs. 1.8 and 4.0 vs. 2.2 for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean of 10.2 vs. 5.0 and 10.9 vs. 5.5 for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

Data Source: An analysis of data from a clinical trial examining a combined pharmacologic and behavioral intervention for smoking cessation.

Disclosures: The main investigator reported that neither she nor her colleagues had relevant conflicts to disclose.

General and smoking-specific weight concerns were more common among white women than among white men and black men and women preparing to quit smoking, but weight concerns were prevalent in all of the groups, according to a study of 301 individuals enrolled in the Chicago STOP Smoking trial.

For example, black women had the highest scores for “body dissatisfaction,” and their scores in regard to smoking-specific weight concerns were statistically similar to those of white women. Men also had substantial smoking-specific weight concerns, which were defined as the belief that smoking can be used for weight control and that quitting smoking leads to weight gain, Lisa A.P. Sánchez-Johnsen, Ph.D., and her colleagues in the department of psychiatry and behavioral neuroscience at the University of Chicago reported online in Addictive Behaviors.

The findings, some of which contradict conventional wisdom about cultural differences in weight and body image between black and white adults, suggest that both groups have specific concerns about weight and body image that could be important in the development of smoking-cessation programs, the investigators said.

Participants were 73 black women, 46 black men, 90 white women, and 92 white men. Overall, general weight concerns (defined by summated scores on the drive for thinness and body dissatisfaction subscales of the Eating Disorders Inventory–2, and the restraint factor of the Three-Factor Eating Questionnaire) were more common in white vs. black participants, and female vs. male participants, but no race by sex interactions were found, the investigators reported (Addict. Behav. 2010 Aug. 6 [doi:10.1016/j.addbeh.2010.08.001

Women had significantly higher mean scores (after controlling for age, body mass index, socioeconomic status, and cigarettes smoked per day) than did men on the specific measure of “drive for thinness” (mean, 4.3 vs. 1.8 and 4.0 vs. 2.2 on a 1-6 scale for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean, 10.2 vs. 5.0 and 10.9 vs. 5.5 on a 0-21 scale for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

White women did, however, have significantly higher scores on the measure of “cognitive restraint,” which refers to the degree to which people consciously monitor and control their food intake (9.5 vs. 5.6, 6.7, and 5.4 on a 0-21 scale for white men, black women, and black men, respectively). This measure might include a cognitive and behavioral component, unlike other dimensions of weight concerns measured in the study, the investigators reported.

Smoking-specific weight concerns also were highest in white women, but the differences were significant only between white women and white and black men (respective scores, 7.7, 6.0, and 6.3). Black women had substantial smoking-specific weight concerns (score, 6.8).

The findings could be key to the development of smoking-cessation programs that address weight concerns for black and white men and women, the researchers concluded.

Major Finding: Women had significantly higher mean scores than men on the specific measure of “drive for thinness” (mean of 4.3 vs. 1.8 and 4.0 vs. 2.2 for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean of 10.2 vs. 5.0 and 10.9 vs. 5.5 for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

Data Source: An analysis of data from a clinical trial examining a combined pharmacologic and behavioral intervention for smoking cessation.

Disclosures: The main investigator reported that neither she nor her colleagues had relevant conflicts to disclose.

General and smoking-specific weight concerns were more common among white women than among white men and black men and women preparing to quit smoking, but weight concerns were prevalent in all of the groups, according to a study of 301 individuals enrolled in the Chicago STOP Smoking trial.

For example, black women had the highest scores for “body dissatisfaction,” and their scores in regard to smoking-specific weight concerns were statistically similar to those of white women. Men also had substantial smoking-specific weight concerns, which were defined as the belief that smoking can be used for weight control and that quitting smoking leads to weight gain, Lisa A.P. Sánchez-Johnsen, Ph.D., and her colleagues in the department of psychiatry and behavioral neuroscience at the University of Chicago reported online in Addictive Behaviors.

The findings, some of which contradict conventional wisdom about cultural differences in weight and body image between black and white adults, suggest that both groups have specific concerns about weight and body image that could be important in the development of smoking-cessation programs, the investigators said.

Participants were 73 black women, 46 black men, 90 white women, and 92 white men. Overall, general weight concerns (defined by summated scores on the drive for thinness and body dissatisfaction subscales of the Eating Disorders Inventory–2, and the restraint factor of the Three-Factor Eating Questionnaire) were more common in white vs. black participants, and female vs. male participants, but no race by sex interactions were found, the investigators reported (Addict. Behav. 2010 Aug. 6 [doi:10.1016/j.addbeh.2010.08.001

Women had significantly higher mean scores (after controlling for age, body mass index, socioeconomic status, and cigarettes smoked per day) than did men on the specific measure of “drive for thinness” (mean, 4.3 vs. 1.8 and 4.0 vs. 2.2 on a 1-6 scale for white and black participants, respectively), and on the specific measure of “body dissatisfaction” (mean, 10.2 vs. 5.0 and 10.9 vs. 5.5 on a 0-21 scale for white and black participants, respectively), but the scores did not differ significantly between whites and blacks.

White women did, however, have significantly higher scores on the measure of “cognitive restraint,” which refers to the degree to which people consciously monitor and control their food intake (9.5 vs. 5.6, 6.7, and 5.4 on a 0-21 scale for white men, black women, and black men, respectively). This measure might include a cognitive and behavioral component, unlike other dimensions of weight concerns measured in the study, the investigators reported.

Smoking-specific weight concerns also were highest in white women, but the differences were significant only between white women and white and black men (respective scores, 7.7, 6.0, and 6.3). Black women had substantial smoking-specific weight concerns (score, 6.8).

The findings could be key to the development of smoking-cessation programs that address weight concerns for black and white men and women, the researchers concluded.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

Statins can inhibit the beneficial effects of rituximab on disease activity in rheumatoid arthritis patients, according to the findings of a study of 187 patients from the Dutch Rheumatoid Arthritis Monitoring registry.

After 6 months of treatment, the mean reduction in disease activity score using 28 joint counts (DAS28) was lower in 23 of 187 RA patients who were treated with both statins and rituximab (RTX) than in 164 patients treated with RTX alone (mean reduction of 0.5 vs. 1.0 point). The difference was of borderline statistical significance after adjustment for age, sex, baseline DAS28 score, and rheumatoid factor positivity, Dr. E.E.A. Arts of Radboud University Nijmegen (the Netherlands) Medical Center and colleagues reported online in the Oct. 18 issue of Annals of the Rheumatic Diseases.

Compared with the RTX-only patients, those exposed to statins also had a shorter effective period following RTX treatment (median of 7 months vs. 9 months), and were more likely to experience a failure event (hazard ratio, 2.3), after adjustment for the same confounders, the investigators said (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.136093]).

All patients in the DREAM registry were included in the prospective cohort study, and all received 50 mg of prednisone with the first RTX infusion. Patients in both the RTX plus statin and the RTX-only groups had similar DAS28 scores at baseline. The statin group was older (mean age, 66 vs. 58 years) and included a greater proportion of men than the RTX-only group (48% vs. 20%), but the groups were otherwise similar.

Although the study had a small sample size, it was sufficiently powered and showed a clinically relevant difference in DAS28 score changes over the 6-month study period, the investigators noted, adding that lack of randomization was another limitation of little concern, because "confounding by indication is unlikely."

More studies to replicate these findings and measure the magnitude of the effect are needed, they said.

"Significant interactions of statins with RTX in RA have not previously been shown. A critical review of common practice regarding concomitant use of statins in RTX-treated patients with RA is needed," they concluded.

The DREAM registry is funded by the Dutch affiliations of Wyeth Pharmaceuticals, Abbott Laboratories, Schering-Plough Corp., Roche Pharmaceuticals, UCB Pharma Inc., and Bristol-Myers Squibb Co.

The recent headway of two treatments for addiction to heroin and other opiates represents a major advancement and has the potential to put opioid addiction therapy within the purview of primary care providers, according to several experts.

National Institute on Drug Abuse

The approval in October of a new indication for an injectable, extended-release formulation of the opioid receptor antagonist naltrexone, marketed as Vivitrol (Alkermes Inc.), now allows for its use as a treatment for preventing relapses in people who have undergone opioid detoxification. Moreover, an implantable form of the opiate agonist buprenorphine, that delivers a continuous dose of medication for up to 6 months, showed promise in a recently published phase III study.

Both advances have the potential for broadening access to care and improving treatment compliance, according to Dr. Nora D. Volkow, a psychiatrist and the director of the National Institute on Drug Abuse (NIDA).

Ultimately, the treatment options could help improve outcomes for the more than 800,000 people in the United States who are believed to be addicted to heroin, and the 1.85 million who abuse or are dependent on opioid pain relievers, such as Oxycontin and Vicodin, Dr. Volkow said in an interview.

Dr. Volkow said that she envisions an expanded role not just for psychiatrists and addiction medicine specialists, who have traditionally managed opioid-dependent patients, but also for primary care doctors and infectious disease specialists who could provide integrated care for heroin-addicted HIV patients.

Access to care for all people with opioid dependence would be improved if more physicians adopt these new treatment options. Compliance also would improve, largely because both treatments involve extended dosing, Dr. Volkow pointed out

Older treatment options such as methadone and daily sublingual buprenorphine can be effective, particularly when combined with counseling. However, they require more frequent dosing, a daunting hurdle for patients whose ability to be compliant is easily derailed by the forces of craving and the risk of relapse. Furthermore, diversion is an issue with sublingual buprenorphine. And many treatment centers reject the idea of using opiates, even synthetic ones, to treat opioid addiction.

Vivitrol, which was approved in 2006 for the treatment of alcohol dependence, is the first non-narcotic, nonaddictive extended-release medication approved to treat opioid dependence. In a 6-month study of 250 patients, monthly intramuscular injection with the drug proved significantly more effective than placebo for preventing relapses: 36% of treated patients, compared with 23% of those on placebo, used no opioids between the 5th week and the end of the study, according to a statement released by the Food and Drug Administration following its approval of this new indication.

Importantly, all the patients in the trial were completing or had recently completed detoxification and were no longer physically dependent on opioids at baseline.

Despite concerns that patients wouldn’t return for repeat injections, Dr. Volkow said she was particularly encouraged to learn that patients did return routinely in the Russian studies on which the new Vivitrol approval was based.

“Patients were very compliant, which was not necessarily predictable,” she explained. “That made me very excited about this particular medication.”

NIDA is funding a study to replicate and expand upon the Russian studies, to verify that U.S. patients would respond similarly. Investigators also plan to compare outcomes associated with Vivitrol vs. buprenorphine, she said.

In a phase III, randomized controlled study of 108 opioid addicts, implantable buprenorphine was associated with a 6-month significant reduction in drug use among 40% of patients, compared with 20% of those taking placebo.

About 60% of the treated participants completed the study without experiencing withdrawal symptoms or cravings that compelled them to drop out. By comparison, studies of the daily sublingual dose of buprenorphine currently available for use showed a median adherence of only 40 days in clinical settings, and retention rates in 6-month clinical trials were only 35%-38% (JAMA 2010;14:1576-83).

Dr. Volkow said that she hopes implantable buprenorphine will soon become part of the arsenal of weapons against the crippling effects of opioid addiction.

But will more primary care physicians and other specialists start to provide addiction care?

“It’s going to be very interesting to watch,” said Dr. Peter D. Friedmann, professor of medicine and community health at Brown University, Providence, R.I.

“Traditionally, primary care doctors have not been very proactive in taking on the care of these patients,” he said.

However, he suggested that opioid dependence could be the new depression. That is, until the advent of relatively safe and easy-to-use depression medications in the early 1980s, the care of depressed patients was not seen as the purview of primary care doctors, but now they are routinely treating depression in their practices. It remains unclear whether that will be the case now, however, given that Vivitrol has been available for years for the treatment of alcohol abuse and primary care doctors have not exactly “flocked to take that on,” he said.

These are complicated patients who at times are difficult to manage, and there is still a lot of stigma and unease among doctors about how to care for them, he explained.

“It’s clearly a positive for the field. It’s going to improve things, but is it going to be a panacea? I doubt it,” he said, adding: “I’m cautiously optimistic.”

Dr. Thomas Kosten, former director of the U.S. National Buprenorphine Implementation Program and currently a professor in the psychiatry and neuroscience departments at Baylor College of Medicine, Houston, also expressed cautious optimism about expanded access to care for opioid-dependent patients.

“I can’t imagine psychiatrists performing the minor surgical procedure involved with buprenorphine implants, but it is certainly within the purview of many internists and general practitioners,” he said, noting that in many cases in primary care, the machinery is already set up for providing such office procedures, and – in the case of Vivitrol – for providing injections.

“In fact, they would be more comfortable and better equipped to do this,” said Dr. Kosten, who also is research director of the Veterans Health Administration’s National Substance Use Disorders Quality Enhancement Research Initiative, based in Houston.

A challenge might be in ensuring that patients receive counseling as needed, but research is increasingly indicating that patients can do well on medications alone if they remain compliant, so concern may be moot, he added.

Another deterrent for many providers has been the requirement of government-sponsored training and oversight of physicians who wish to prescribe buprenorphine.

Dr. H. Berryman Edwards, a psychiatrist in private practice in Bellevue, Wash., and an outspoken critic of the U.S. Drug Enforcement Administration’s “disruptive” approach to the oversight of physicians who do prescribe buprenorphine, agreed that psychiatrists aren’t likely to use the implantable formulation. But he acknowledged that for primary care doctors and others who embrace this new formulation, it eliminates many of the concerns about diversion and compliance that have deterred physicians from using the treatment in the past.

It will take a certain level of commitment from those who have a desire to use these treatments in the primary care office setting, said Dr. Andrew J. Saxon, a professor of psychiatry and behavioral sciences at the University of Washington, Seattle, and one of the site investigators for the implantable buprenorphine study.

While most primary care doctors probably won’t have an interest, those who are willing to learn the implantation procedure – which can be a bit time consuming – and who undergo the required training, will certainly be able to provide this treatment in the office setting. In some cases, it may be that the implants are done elsewhere but patients are followed by their primary care physician, he said.

Vivitrol, on the other hand, could quite easily be provided in the primary care setting. He described Vivitrol as “a pharmacological treatment that is almost perfection,” largely because of the requirement that patients be off opioids before they can receive it.

Vivitrol is safe, he said, with one exception: Patients receiving it will have a decreased tolerance for opioids, and may be at an increased risk of overdose. The overdose risk must be closely monitored, but overall, the treatment has the potential to be a tremendous advantage, Dr. Saxon said.

Dr. Volkow and Dr. Edwards reported having no conflicts of interest. Dr. Friedmann has studied Vivitrol and has received in-kind donations of the medication for his research. He is on the speakers bureau for Reckitt Benckiser Pharmaceuticals, the maker of the sublingual formulation of buprenorphine. Dr. Kosten has served as a consultant to Reckitt Benckiser and to Alkermes. He has served on the data safety monitoring board for Titan Pharmaceuticals, which makes the implantable buprenorphine. Dr. Saxon has served as a consultant to Reckitt Benckiser, and was a site investigator for the Titan-sponsored buprenorphine implant study.

The recent headway of two treatments for addiction to heroin and other opiates represents a major advancement and has the potential to put opioid addiction therapy within the purview of primary care providers, according to several experts.

National Institute on Drug Abuse

The approval in October of a new indication for an injectable, extended-release formulation of the opioid receptor antagonist naltrexone, marketed as Vivitrol (Alkermes Inc.), now allows for its use as a treatment for preventing relapses in people who have undergone opioid detoxification. Moreover, an implantable form of the opiate agonist buprenorphine, that delivers a continuous dose of medication for up to 6 months, showed promise in a recently published phase III study.

Both advances have the potential for broadening access to care and improving treatment compliance, according to Dr. Nora D. Volkow, a psychiatrist and the director of the National Institute on Drug Abuse (NIDA).

Ultimately, the treatment options could help improve outcomes for the more than 800,000 people in the United States who are believed to be addicted to heroin, and the 1.85 million who abuse or are dependent on opioid pain relievers, such as Oxycontin and Vicodin, Dr. Volkow said in an interview.

Dr. Volkow said that she envisions an expanded role not just for psychiatrists and addiction medicine specialists, who have traditionally managed opioid-dependent patients, but also for primary care doctors and infectious disease specialists who could provide integrated care for heroin-addicted HIV patients.

Access to care for all people with opioid dependence would be improved if more physicians adopt these new treatment options. Compliance also would improve, largely because both treatments involve extended dosing, Dr. Volkow pointed out

Older treatment options such as methadone and daily sublingual buprenorphine can be effective, particularly when combined with counseling. However, they require more frequent dosing, a daunting hurdle for patients whose ability to be compliant is easily derailed by the forces of craving and the risk of relapse. Furthermore, diversion is an issue with sublingual buprenorphine. And many treatment centers reject the idea of using opiates, even synthetic ones, to treat opioid addiction.

Vivitrol, which was approved in 2006 for the treatment of alcohol dependence, is the first non-narcotic, nonaddictive extended-release medication approved to treat opioid dependence. In a 6-month study of 250 patients, monthly intramuscular injection with the drug proved significantly more effective than placebo for preventing relapses: 36% of treated patients, compared with 23% of those on placebo, used no opioids between the 5th week and the end of the study, according to a statement released by the Food and Drug Administration following its approval of this new indication.

Importantly, all the patients in the trial were completing or had recently completed detoxification and were no longer physically dependent on opioids at baseline.

Despite concerns that patients wouldn’t return for repeat injections, Dr. Volkow said she was particularly encouraged to learn that patients did return routinely in the Russian studies on which the new Vivitrol approval was based.

“Patients were very compliant, which was not necessarily predictable,” she explained. “That made me very excited about this particular medication.”

NIDA is funding a study to replicate and expand upon the Russian studies, to verify that U.S. patients would respond similarly. Investigators also plan to compare outcomes associated with Vivitrol vs. buprenorphine, she said.

In a phase III, randomized controlled study of 108 opioid addicts, implantable buprenorphine was associated with a 6-month significant reduction in drug use among 40% of patients, compared with 20% of those taking placebo.

About 60% of the treated participants completed the study without experiencing withdrawal symptoms or cravings that compelled them to drop out. By comparison, studies of the daily sublingual dose of buprenorphine currently available for use showed a median adherence of only 40 days in clinical settings, and retention rates in 6-month clinical trials were only 35%-38% (JAMA 2010;14:1576-83).

Dr. Volkow said that she hopes implantable buprenorphine will soon become part of the arsenal of weapons against the crippling effects of opioid addiction.

But will more primary care physicians and other specialists start to provide addiction care?

“It’s going to be very interesting to watch,” said Dr. Peter D. Friedmann, professor of medicine and community health at Brown University, Providence, R.I.

“Traditionally, primary care doctors have not been very proactive in taking on the care of these patients,” he said.

However, he suggested that opioid dependence could be the new depression. That is, until the advent of relatively safe and easy-to-use depression medications in the early 1980s, the care of depressed patients was not seen as the purview of primary care doctors, but now they are routinely treating depression in their practices. It remains unclear whether that will be the case now, however, given that Vivitrol has been available for years for the treatment of alcohol abuse and primary care doctors have not exactly “flocked to take that on,” he said.

These are complicated patients who at times are difficult to manage, and there is still a lot of stigma and unease among doctors about how to care for them, he explained.

“It’s clearly a positive for the field. It’s going to improve things, but is it going to be a panacea? I doubt it,” he said, adding: “I’m cautiously optimistic.”

Dr. Thomas Kosten, former director of the U.S. National Buprenorphine Implementation Program and currently a professor in the psychiatry and neuroscience departments at Baylor College of Medicine, Houston, also expressed cautious optimism about expanded access to care for opioid-dependent patients.

“I can’t imagine psychiatrists performing the minor surgical procedure involved with buprenorphine implants, but it is certainly within the purview of many internists and general practitioners,” he said, noting that in many cases in primary care, the machinery is already set up for providing such office procedures, and – in the case of Vivitrol – for providing injections.

“In fact, they would be more comfortable and better equipped to do this,” said Dr. Kosten, who also is research director of the Veterans Health Administration’s National Substance Use Disorders Quality Enhancement Research Initiative, based in Houston.

A challenge might be in ensuring that patients receive counseling as needed, but research is increasingly indicating that patients can do well on medications alone if they remain compliant, so concern may be moot, he added.

Another deterrent for many providers has been the requirement of government-sponsored training and oversight of physicians who wish to prescribe buprenorphine.

Dr. H. Berryman Edwards, a psychiatrist in private practice in Bellevue, Wash., and an outspoken critic of the U.S. Drug Enforcement Administration’s “disruptive” approach to the oversight of physicians who do prescribe buprenorphine, agreed that psychiatrists aren’t likely to use the implantable formulation. But he acknowledged that for primary care doctors and others who embrace this new formulation, it eliminates many of the concerns about diversion and compliance that have deterred physicians from using the treatment in the past.

It will take a certain level of commitment from those who have a desire to use these treatments in the primary care office setting, said Dr. Andrew J. Saxon, a professor of psychiatry and behavioral sciences at the University of Washington, Seattle, and one of the site investigators for the implantable buprenorphine study.

While most primary care doctors probably won’t have an interest, those who are willing to learn the implantation procedure – which can be a bit time consuming – and who undergo the required training, will certainly be able to provide this treatment in the office setting. In some cases, it may be that the implants are done elsewhere but patients are followed by their primary care physician, he said.

Vivitrol, on the other hand, could quite easily be provided in the primary care setting. He described Vivitrol as “a pharmacological treatment that is almost perfection,” largely because of the requirement that patients be off opioids before they can receive it.

Vivitrol is safe, he said, with one exception: Patients receiving it will have a decreased tolerance for opioids, and may be at an increased risk of overdose. The overdose risk must be closely monitored, but overall, the treatment has the potential to be a tremendous advantage, Dr. Saxon said.

Dr. Volkow and Dr. Edwards reported having no conflicts of interest. Dr. Friedmann has studied Vivitrol and has received in-kind donations of the medication for his research. He is on the speakers bureau for Reckitt Benckiser Pharmaceuticals, the maker of the sublingual formulation of buprenorphine. Dr. Kosten has served as a consultant to Reckitt Benckiser and to Alkermes. He has served on the data safety monitoring board for Titan Pharmaceuticals, which makes the implantable buprenorphine. Dr. Saxon has served as a consultant to Reckitt Benckiser, and was a site investigator for the Titan-sponsored buprenorphine implant study.

The recent headway of two treatments for addiction to heroin and other opiates represents a major advancement and has the potential to put opioid addiction therapy within the purview of primary care providers, according to several experts.

National Institute on Drug Abuse

The approval in October of a new indication for an injectable, extended-release formulation of the opioid receptor antagonist naltrexone, marketed as Vivitrol (Alkermes Inc.), now allows for its use as a treatment for preventing relapses in people who have undergone opioid detoxification. Moreover, an implantable form of the opiate agonist buprenorphine, that delivers a continuous dose of medication for up to 6 months, showed promise in a recently published phase III study.

Both advances have the potential for broadening access to care and improving treatment compliance, according to Dr. Nora D. Volkow, a psychiatrist and the director of the National Institute on Drug Abuse (NIDA).

Ultimately, the treatment options could help improve outcomes for the more than 800,000 people in the United States who are believed to be addicted to heroin, and the 1.85 million who abuse or are dependent on opioid pain relievers, such as Oxycontin and Vicodin, Dr. Volkow said in an interview.

Dr. Volkow said that she envisions an expanded role not just for psychiatrists and addiction medicine specialists, who have traditionally managed opioid-dependent patients, but also for primary care doctors and infectious disease specialists who could provide integrated care for heroin-addicted HIV patients.

Access to care for all people with opioid dependence would be improved if more physicians adopt these new treatment options. Compliance also would improve, largely because both treatments involve extended dosing, Dr. Volkow pointed out

Older treatment options such as methadone and daily sublingual buprenorphine can be effective, particularly when combined with counseling. However, they require more frequent dosing, a daunting hurdle for patients whose ability to be compliant is easily derailed by the forces of craving and the risk of relapse. Furthermore, diversion is an issue with sublingual buprenorphine. And many treatment centers reject the idea of using opiates, even synthetic ones, to treat opioid addiction.

Vivitrol, which was approved in 2006 for the treatment of alcohol dependence, is the first non-narcotic, nonaddictive extended-release medication approved to treat opioid dependence. In a 6-month study of 250 patients, monthly intramuscular injection with the drug proved significantly more effective than placebo for preventing relapses: 36% of treated patients, compared with 23% of those on placebo, used no opioids between the 5th week and the end of the study, according to a statement released by the Food and Drug Administration following its approval of this new indication.

Importantly, all the patients in the trial were completing or had recently completed detoxification and were no longer physically dependent on opioids at baseline.

Despite concerns that patients wouldn’t return for repeat injections, Dr. Volkow said she was particularly encouraged to learn that patients did return routinely in the Russian studies on which the new Vivitrol approval was based.

“Patients were very compliant, which was not necessarily predictable,” she explained. “That made me very excited about this particular medication.”

NIDA is funding a study to replicate and expand upon the Russian studies, to verify that U.S. patients would respond similarly. Investigators also plan to compare outcomes associated with Vivitrol vs. buprenorphine, she said.

In a phase III, randomized controlled study of 108 opioid addicts, implantable buprenorphine was associated with a 6-month significant reduction in drug use among 40% of patients, compared with 20% of those taking placebo.

About 60% of the treated participants completed the study without experiencing withdrawal symptoms or cravings that compelled them to drop out. By comparison, studies of the daily sublingual dose of buprenorphine currently available for use showed a median adherence of only 40 days in clinical settings, and retention rates in 6-month clinical trials were only 35%-38% (JAMA 2010;14:1576-83).

Dr. Volkow said that she hopes implantable buprenorphine will soon become part of the arsenal of weapons against the crippling effects of opioid addiction.

But will more primary care physicians and other specialists start to provide addiction care?

“It’s going to be very interesting to watch,” said Dr. Peter D. Friedmann, professor of medicine and community health at Brown University, Providence, R.I.

“Traditionally, primary care doctors have not been very proactive in taking on the care of these patients,” he said.

However, he suggested that opioid dependence could be the new depression. That is, until the advent of relatively safe and easy-to-use depression medications in the early 1980s, the care of depressed patients was not seen as the purview of primary care doctors, but now they are routinely treating depression in their practices. It remains unclear whether that will be the case now, however, given that Vivitrol has been available for years for the treatment of alcohol abuse and primary care doctors have not exactly “flocked to take that on,” he said.

These are complicated patients who at times are difficult to manage, and there is still a lot of stigma and unease among doctors about how to care for them, he explained.

“It’s clearly a positive for the field. It’s going to improve things, but is it going to be a panacea? I doubt it,” he said, adding: “I’m cautiously optimistic.”

Dr. Thomas Kosten, former director of the U.S. National Buprenorphine Implementation Program and currently a professor in the psychiatry and neuroscience departments at Baylor College of Medicine, Houston, also expressed cautious optimism about expanded access to care for opioid-dependent patients.

“I can’t imagine psychiatrists performing the minor surgical procedure involved with buprenorphine implants, but it is certainly within the purview of many internists and general practitioners,” he said, noting that in many cases in primary care, the machinery is already set up for providing such office procedures, and – in the case of Vivitrol – for providing injections.

“In fact, they would be more comfortable and better equipped to do this,” said Dr. Kosten, who also is research director of the Veterans Health Administration’s National Substance Use Disorders Quality Enhancement Research Initiative, based in Houston.

A challenge might be in ensuring that patients receive counseling as needed, but research is increasingly indicating that patients can do well on medications alone if they remain compliant, so concern may be moot, he added.

Another deterrent for many providers has been the requirement of government-sponsored training and oversight of physicians who wish to prescribe buprenorphine.

Dr. H. Berryman Edwards, a psychiatrist in private practice in Bellevue, Wash., and an outspoken critic of the U.S. Drug Enforcement Administration’s “disruptive” approach to the oversight of physicians who do prescribe buprenorphine, agreed that psychiatrists aren’t likely to use the implantable formulation. But he acknowledged that for primary care doctors and others who embrace this new formulation, it eliminates many of the concerns about diversion and compliance that have deterred physicians from using the treatment in the past.

It will take a certain level of commitment from those who have a desire to use these treatments in the primary care office setting, said Dr. Andrew J. Saxon, a professor of psychiatry and behavioral sciences at the University of Washington, Seattle, and one of the site investigators for the implantable buprenorphine study.

While most primary care doctors probably won’t have an interest, those who are willing to learn the implantation procedure – which can be a bit time consuming – and who undergo the required training, will certainly be able to provide this treatment in the office setting. In some cases, it may be that the implants are done elsewhere but patients are followed by their primary care physician, he said.

Vivitrol, on the other hand, could quite easily be provided in the primary care setting. He described Vivitrol as “a pharmacological treatment that is almost perfection,” largely because of the requirement that patients be off opioids before they can receive it.

Vivitrol is safe, he said, with one exception: Patients receiving it will have a decreased tolerance for opioids, and may be at an increased risk of overdose. The overdose risk must be closely monitored, but overall, the treatment has the potential to be a tremendous advantage, Dr. Saxon said.

Dr. Volkow and Dr. Edwards reported having no conflicts of interest. Dr. Friedmann has studied Vivitrol and has received in-kind donations of the medication for his research. He is on the speakers bureau for Reckitt Benckiser Pharmaceuticals, the maker of the sublingual formulation of buprenorphine. Dr. Kosten has served as a consultant to Reckitt Benckiser and to Alkermes. He has served on the data safety monitoring board for Titan Pharmaceuticals, which makes the implantable buprenorphine. Dr. Saxon has served as a consultant to Reckitt Benckiser, and was a site investigator for the Titan-sponsored buprenorphine implant study.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries Ltd. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in disability progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset when compared with placebo in the randomized phase of the trial but also was associated in the open-label extension phase with a delay of nearly 3 years in the time to conversion to CDMS when compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent brain volume change was also significantly lower over the entire study period in patients who received early treatment with GA (-0.99% vs. -1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable for delaying full conversion.

“Hopefully in the near future there will be tools to determine if the patients with CIS should be treated with GA or interferon-beta,” he said.

In a study published earlier this year, Dr. Raman and his colleagues found that interferon-beta was effective in mice with experimental autoimmune encephalomyelitis, the animal model of MS, that was initiated by T helper type 1 cells. However, interferon-beta worsened disease that had been initiated by T helper type 17 cells (Nat. Med. 2010;16:406-12).

The findings were replicated in serum from human patients with relapsing-remitting MS, and if verified in an expanded human trial, a simple blood test could be developed to determine which type of T helper cell is predominantly responsible for the disease in a patient, and therefore whether – and, perhaps, which – treatment would be of benefit.

The clinical results from PreCISe were significant, but modest, and Dr. Raman said that he is confident that the benefits of early treatment would have been even greater if the patients could have been stratified by disease type and treated accordingly.

“The findings that we reported in the Nature Medicine paper, when validated and commercialized, would achieve that objective,” he said.

Dr. Comi reported that he has received personal compensation for advisory board and consulting activities from Teva Pharmaceuticals, Novartis, Sanofi-Aventis, Merck-Serono, and Bayer Schering. He has also received honoraria for speaking activities from these companies, as well as from Biogen-Dompé. Dr. Filippi also reported financial relationship with many of these companies, including Teva. Dr. Raman reported that his research was supported by grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries Ltd. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in disability progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset when compared with placebo in the randomized phase of the trial but also was associated in the open-label extension phase with a delay of nearly 3 years in the time to conversion to CDMS when compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent brain volume change was also significantly lower over the entire study period in patients who received early treatment with GA (-0.99% vs. -1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable for delaying full conversion.

“Hopefully in the near future there will be tools to determine if the patients with CIS should be treated with GA or interferon-beta,” he said.

In a study published earlier this year, Dr. Raman and his colleagues found that interferon-beta was effective in mice with experimental autoimmune encephalomyelitis, the animal model of MS, that was initiated by T helper type 1 cells. However, interferon-beta worsened disease that had been initiated by T helper type 17 cells (Nat. Med. 2010;16:406-12).

The findings were replicated in serum from human patients with relapsing-remitting MS, and if verified in an expanded human trial, a simple blood test could be developed to determine which type of T helper cell is predominantly responsible for the disease in a patient, and therefore whether – and, perhaps, which – treatment would be of benefit.

The clinical results from PreCISe were significant, but modest, and Dr. Raman said that he is confident that the benefits of early treatment would have been even greater if the patients could have been stratified by disease type and treated accordingly.

“The findings that we reported in the Nature Medicine paper, when validated and commercialized, would achieve that objective,” he said.

Dr. Comi reported that he has received personal compensation for advisory board and consulting activities from Teva Pharmaceuticals, Novartis, Sanofi-Aventis, Merck-Serono, and Bayer Schering. He has also received honoraria for speaking activities from these companies, as well as from Biogen-Dompé. Dr. Filippi also reported financial relationship with many of these companies, including Teva. Dr. Raman reported that his research was supported by grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Patients with clinically isolated syndrome who receive early treatment with glatiramer acetate have more than a 40% reduction in the risk of developing multiple sclerosis, compared with those whose treatment is delayed, according to findings from a prospectively planned 5-year follow-up of patient in the phase III PreCISe study.

After a 2-year extension phase of the 3-year double-blind, placebo-controlled study, 33% of 80 patients who had received early treatment with glatiramer acetate (GA) developed clinically definite multiple sclerosis (CDMS), compared with 50% of 118 patients who began treatment at the end of the initial 3-year double-blind phase. Each patient received 20 mg of GA daily by subcutaneous injection.

GA is marketed as Copaxone by Teva Pharmaceutical Industries Ltd. It is approved in 51 countries, including the United States, and is indicated for reducing the frequency of relapses in relapsing-remitting MS, including those who have experienced a first clinical episode and who have MS features on MRI.

In the Teva-sponsored study, disability progression, as measured by the Expanded Disability Status Scale, occurred in only 21% of patients over 5 years. No differences in disability progression were noted between the early and delayed treatment groups, according to the principal investigator, Dr. Giancarlo Comi, director of the department of neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy.

“The long-term study results support the benefit of early GA treatment in delaying conversion to CDMS and in reducing MRI burden, including less accumulation of irreversible brain damage,” Dr. Comi said in an interview.

Patients in this 2-year extension phase were initially enrolled in the double-blind phase of PreCISe, and were randomized to receive active early treatment with GA or placebo. Findings from a planned interim analysis showed that treatment reduced the risk of CDMS by 44% versus placebo, and delayed disease progression by 722 days vs. 336 days. That phase was stopped after a mean exposure of 2.32 years, and patients were offered the opportunity to enter the open-label extension phase, during which all patients received treatment.

Early treatment reduced the risk of CDMS and delayed its onset when compared with placebo in the randomized phase of the trial but also was associated in the open-label extension phase with a delay of nearly 3 years in the time to conversion to CDMS when compared with delayed treatment.

MRI findings from the PreCISe study, which were presented in a separate session at ECTRIMS, also confirmed the importance of early treatment, according to the principal investigator for that portion of the study, Dr. Massimo Filippi, director of the Neuroimaging Research Unit and professor of clinical neurology at the Scientific Institute and University Ospedale San Raffaele, Milan, and his colleagues.

Early initiation of treatment with GA reduced disease activity and slowed the accumulation of brain atrophy over 5 years as demonstrated by MRI. The early treatment group had significantly fewer new T2 lesions – an indicator of disease activity – and lower T2 lesion volume – a predictor of disease progression – than did the delayed treatment group, the investigators found.

Percent brain volume change was also significantly lower over the entire study period in patients who received early treatment with GA (-0.99% vs. -1.27%), they said.

The drop-out rate in the 5 years of the PreCISe study was 33% among treated patients, which attests to the established long-term safety profile in patients with relapsing-remitting disease, Dr. Comi said.

“It is very difficult to compare Copaxone to other interferons studied in CIS due to the differences in the type of patients included in each study, but basically the results are comparable, although only Copaxone showed an effect on brain atrophy after 5 years,” Dr. Comi said. He added that the efficacy and safety results of this study establish the importance of early treatment with this drug in CIS patients presenting with positive brain MRI.

Chander Raman, Ph.D., an MS researcher and associate professor of clinical immunology and rheumatology at the University of Alabama at Birmingham, said the PreCISe findings confirm what neurologists have started to believe about managing CIS in adults – that treatment at the first clinical diagnosis of CIS is preferable for delaying full conversion.

“Hopefully in the near future there will be tools to determine if the patients with CIS should be treated with GA or interferon-beta,” he said.

In a study published earlier this year, Dr. Raman and his colleagues found that interferon-beta was effective in mice with experimental autoimmune encephalomyelitis, the animal model of MS, that was initiated by T helper type 1 cells. However, interferon-beta worsened disease that had been initiated by T helper type 17 cells (Nat. Med. 2010;16:406-12).

The findings were replicated in serum from human patients with relapsing-remitting MS, and if verified in an expanded human trial, a simple blood test could be developed to determine which type of T helper cell is predominantly responsible for the disease in a patient, and therefore whether – and, perhaps, which – treatment would be of benefit.

The clinical results from PreCISe were significant, but modest, and Dr. Raman said that he is confident that the benefits of early treatment would have been even greater if the patients could have been stratified by disease type and treated accordingly.

“The findings that we reported in the Nature Medicine paper, when validated and commercialized, would achieve that objective,” he said.

Dr. Comi reported that he has received personal compensation for advisory board and consulting activities from Teva Pharmaceuticals, Novartis, Sanofi-Aventis, Merck-Serono, and Bayer Schering. He has also received honoraria for speaking activities from these companies, as well as from Biogen-Dompé. Dr. Filippi also reported financial relationship with many of these companies, including Teva. Dr. Raman reported that his research was supported by grants from the National Multiple Sclerosis Society and the National Institutes of Health.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Taking at least 75 mg of aspirin daily for several years reduces significantly the long-term risks of developing colorectal cancer and of dying from the disease, according to an analysis of five randomized trials involving more than 14,000 patients.

© Darren Hester/Fotolia.com

The 20-year incidence of colon cancer was reduced by 24% (hazard ratio 0.76) and 20-year mortality by 35% (HR 0.65) in patients who took aspirin and were compared with a control group in pooled data from four of the trials, reported Dr. Peter M. Rothwell, a professor of clinical neurology and founder of the stroke prevention research unit at the University of Oxford, U.K., and his colleagues.

Allocation to aspirin in those trials did not, however, reduce the overall risk of developing rectal cancer (HR 0.90), according to findings published online in the Oct. 22 issue of The Lancet.

All of the trials were designed to look at prevention of vascular events, not colorectal cancer specifically. The four pooled trials compared aspirin with either placebo or no treatment. The new analysis shows that 391 of 14,033 patients (2.8%) developed colon cancer after a median of 6 years of scheduled treatment and at a median follow-up of 18.3 years.

Of note was a finding that in studies for which data were available, patients allocated to receive aspirin had a significantly reduced risk of cancer of the proximal colon (HR 0.45), but not the distal colon (HR 1.10). Similarly, patients on aspirin had a significantly reduced risk of fatal proximal colon cancers (HR 0.34), but not fatal distal colon cancers (HR 1.21), the investigators said (Lancet 2010 Oct. 22 [doi:10.1016/S0140-6736(10)61543-7]).

The risk reduction increased with scheduled duration of treatment; patients allocated to take aspirin for at least 5 years had a highly significant reduction of about 70% in the risk of proximal colon cancer (HR 0.35). They also had a significantly reduced incidence of rectal cancer but not distal colon cancer.

Furthermore, no increase in benefit was seen with doses above 75 mg daily, according to an analysis of data from the fifth study and one of the four controlled studies, both of which compared various doses of aspirin. An absolute reduction of 1.76% in 20-year risk of any fatal colorectal cancer was seen with doses ranging from 75 mg daily to 300 mg daily; it persisted when the analysis was limited to patients allocated to 75 mg daily. In one study, which compared a 30 mg and 283 mg daily dose, however, mortality was significantly higher with the 30 mg dose (odds ratio 2.02).

In a previous report of data from two of the trials in the current analysis, the investigators showed that the 20-year incidence of colorectal cancer was reduced by 30% in patients who used high-dose aspirin for 5 years. The current findings are important in that they show a similar effect with doses as low as 75 mg daily, they said.

The study has some potential limitations, including the possibility that trial participants had more investigations because adverse treatment effects, and therefore may have had an earlier diagnosis of colorectal adenoma or cancer than they would have had otherwise. Also, the number of cancers in the study that compared 30-mg and 283-mg doses was small, which limits the certainty of the effect.

Nonetheless, the finding of an approximately 1.5% reduction in absolute long-term risk of colorectal cancer does have implications for clinical practice, the investigators said. “In patients with an established indication for long-term antiplatelet treatment, such as in secondary prevention of vascular disease, this additional benefit will favor treatment with aspirin over other antiplatelet drugs, assuming that other drugs do not afford similar benefit,” they wrote.

Also, in light of the recently “finely balanced” risk-benefit debate over long-term benefits vs. major bleeding risk with aspirin therapy to reduce the risk of ischemic vascular events, the current findings might “tip the balance” back to favoring treatment, they argued.

“The five trials we studied all predated endoscopic screening for adenomas, which also reduced colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumors might allow less frequent screening, and the prevention of proximal colonic cancer by aspirin, which would not be identified by sigmoidoscopy screening and for which colonoscopy screening is only partly effective, is clearly important,” they wrote.

Since the “very substantial” reduction in proximal colon cancers in patients on aspirin therapy in this study might be a result of an effect on aggressive non-polypoid or de novo cancers, which are often flat and can be easily missed on colonoscopy, it is probable that screening and aspirin therapy for preventing colorectal cancer will be synergistic, they concluded.

Dr. Rothwell and coauthor, Dr. Bo Norrving, reported receiving honoraria for giving talks and serving on advisory boards and clinical trial committees for AstraZeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, and Servier – all of which have an interest in antiplatelet agents. Dr. Ale Agra reported receiving honoraria for serving on advisory boards and research funding from Boehringer Ingelheim. The remaining study authors reported having no disclosures.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31%, compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O’Connor reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so?are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O’Connor of St. Michael’s Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course ... we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

All three sources disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31%, compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O’Connor reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so?are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O’Connor of St. Michael’s Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course ... we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

All three sources disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

Teriflunomide, a novel oral disease-modifying drug, significantly reduced the annualized relapse rate and the risk of disability progression in relapsing multiple sclerosis by about 30% in a 2-year, phase III trial.

The study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients with Multiple Sclerosis (TEMSO), which was sponsored by Sanofi-Aventis, randomized 1,088 patients to receive a single daily dose of 7 mg or 14 mg of teriflunomide or placebo.

The primary end point – the annualized relapse rate – was significantly lower among the 7-mg and 14-mg groups (0.370 and 0.369, respectively) than it was in placebo-treated patients (0.539). These rates represented a statistically significant reduction of 31%, compared with placebo. Patients in the 14-mg group also experienced a significant 30% reduction in the risk of disability progression, Dr. Paul O’Connor reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Teriflunomide is the active metabolite of leflunomide, a synthetic, low-molecular-weight drug that was approved by the Food and Drug Administration in 1998 for the treatment of rheumatoid arthritis. The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so?are not yet completely understood. Inhibition of pyrimidine biosynthesis (via suppression of DHODH) and interference with tyrosine kinase activity both appear to be involved.

The treatment groups also experienced a significant reduction in brain disease activity as measured by magnetic resonance imaging (MRI). The burden of disease as determined by total lesion volume, for example, was reduced by 39% and 67% in the 7-mg and 14-mg dose groups, respectively, compared with placebo, said Dr. O’Connor of St. Michael’s Hospital, Toronto. He is the principal investigator for TEMSO.

“In my view, teriflunomide is a safe and effective new monotherapy, and it represents a potential first-line treatment for patients with relapsing MS,” he said during a press briefing on the TEMSO findings.

The safety profile of teriflunomide in this study was a particularly strong, positive point, he added. The overall adverse event rates were the same in the placebo and treatment groups, as were the rates of adverse events leading to permanent discontinuation of treatment. Patients in the teriflunomide group experienced more nausea, diarrhea, increases in alanine transferase, and hair thinning than did those in the placebo group, but these effects were mild. Treatment was generally very well tolerated, and no opportunistic infections occurred, he said.

TEMSO participants were adults aged 18-55 years with relapsing MS and a score of 5.5 or lower on the Expanded Disability Status Scale, and had experienced at least one relapse in the year prior to enrollment, or two relapses in the prior 2 years.

The availability of an oral agent for the treatment of this complex and progressively disabling disease is very good news for MS patients, Dr. Giancarlo Comi said during the press briefing.

“Of course it is central in the management of these patients to have available drugs to modify the disease course ... we are literally entering a period where we can provide patients with much better support than ever before,” said Dr. Comi of Clinica Neurologica, Ospedale San Raffaele, Milan, Italy.

Indeed, other ongoing research is also demonstrating the safety and efficacy of teriflunomide, both as monotherapy and in combination with other treatments, said Dr. Mark Freedman of the Multiple Sclerosis Research Clinic at Ottawa (Canada) Hospital. Dr. Freedman and Dr. Comi are investigators in the TEMSO trial.

For example, an open-label extension of a phase II trial of teriflunomide, which was also reported at the ECTRIMS congress, showed that teriflunomide was well tolerated during 8 years of continuous use following a 36-week double-blind portion of the study. Also, teriflunomide in combination with subcutaneous injection of interferon beta-1a has been shown to improve MRI outcomes in MS patients to a significantly greater extent than does interferon beta-1a and placebo.

Dr. Freedman said that the results from a second phase III study of teriflunomide are expected to be reported in 2012.

All three sources disclosed financial relationships with many companies that manufacture drugs for MS, including Sanofi-Aventis.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1-3 days), 2 (4-7 days), 3 (8-14 days), 4 (15-21 days), and 5 (22-31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate to severe sleep disturbance at baseline because of underlying pain associated with ankylosing spondylitis (AS), were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Men made up most of the patients in the placebo and treatment groups. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 9.9 for the placebo group, 10.3 for the 50-mg group, and 11.1 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (–3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (–3.0 vs. –1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported in the September issue of Arthritis Care & Research.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care & Research 2010:62:1266-71).

Sleep disturbance resulting from axial pain and stiffness is characteristic of the inflammatory back pain in patients with AS, and it contributes to daytime fatigue. The findings of this study – which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores. This finding is consistent with those from prior studies showing that sleep disturbance is predicted by pain at bedtime and during the night, the investigators noted.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

The European Medicines Agency has approved the use of golimumab for treatment of moderate to severe active RA in combination with methotrexate in patients who have not responded adequately to other treatments, including methotrexate. EMEA has also approved golimumab for the treatment of active and progressive psoriatic arthritis in patients who have not responded adequately to other treatments; it can be used alone or in combination with methotrexate. Finally, EMEA has approved it to treat severely active ankylosing spondylitis. Golimumab is used in patients who have not responded adequately to other treatments.

This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from Centocor, Schering-Plough, Wyeth , Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Chugai, Pfizer, MSD, and/or Sanofi-Aventis, and/or owning stock or options in Johnson & Johnson.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1-3 days), 2 (4-7 days), 3 (8-14 days), 4 (15-21 days), and 5 (22-31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate to severe sleep disturbance at baseline because of underlying pain associated with ankylosing spondylitis (AS), were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Men made up most of the patients in the placebo and treatment groups. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 9.9 for the placebo group, 10.3 for the 50-mg group, and 11.1 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (–3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (–3.0 vs. –1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported in the September issue of Arthritis Care & Research.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care & Research 2010:62:1266-71).

Sleep disturbance resulting from axial pain and stiffness is characteristic of the inflammatory back pain in patients with AS, and it contributes to daytime fatigue. The findings of this study – which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores. This finding is consistent with those from prior studies showing that sleep disturbance is predicted by pain at bedtime and during the night, the investigators noted.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

The European Medicines Agency has approved the use of golimumab for treatment of moderate to severe active RA in combination with methotrexate in patients who have not responded adequately to other treatments, including methotrexate. EMEA has also approved golimumab for the treatment of active and progressive psoriatic arthritis in patients who have not responded adequately to other treatments; it can be used alone or in combination with methotrexate. Finally, EMEA has approved it to treat severely active ankylosing spondylitis. Golimumab is used in patients who have not responded adequately to other treatments.

This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from Centocor, Schering-Plough, Wyeth , Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Chugai, Pfizer, MSD, and/or Sanofi-Aventis, and/or owning stock or options in Johnson & Johnson.

The anti–tumor necrosis factor–alpha agent golimumab significantly reduced sleep disturbance and improved health-related quality of life in a randomized placebo-controlled trial of 356 patients with ankylosing spondylitis.

The investigators assessed sleep disturbance using the Jenkins Sleep Evaluation Questionnaire (JSEQ), which asks patients how many times in the past month they have had trouble falling asleep, awakened several times per night, had trouble staying asleep (including waking far too early), and/or awakened after their usual amount of sleep feeling tired and worn out. On the scale, the possible answers for each question were 0 (not at all), 1 (1-3 days), 2 (4-7 days), 3 (8-14 days), 4 (15-21 days), and 5 (22-31 days). Thus, the total JSEQ score ranges from 0 to 20, with higher scores indicating greater sleep disturbance.

Study participants, who had moderate to severe sleep disturbance at baseline because of underlying pain associated with ankylosing spondylitis (AS), were randomized to receive either placebo or treatment with 50 mg or 100 mg of golimumab subcutaneously every 4 weeks.

Men made up most of the patients in the placebo and treatment groups. Their mean time since AS diagnosis was 11 years for the placebo group and 8 years for each golimumab group. The mean baseline JSEQ score was 9.9 for the placebo group, 10.3 for the 50-mg group, and 11.1 for the 100-mg group.

Compared with those in the placebo group, those in the golimumab groups had significantly greater median improvement from baseline on the 0- to 20-point JSEQ at the 14-week follow-up (–3.0 vs. 0.0 point change), and the improvement was sustained at 24-week follow-up (–3.0 vs. –1.0 point change), Dr. Atul Deodhar, medical director of the rheumatology clinic at the Oregon Health & Science University, Portland, and colleagues reported in the September issue of Arthritis Care & Research.

The effect was similar with both the 50- and 100-mg golimumab dose, the investigators noted (Arthritis Care & Research 2010:62:1266-71).

Sleep disturbance resulting from axial pain and stiffness is characteristic of the inflammatory back pain in patients with AS, and it contributes to daytime fatigue. The findings of this study – which is a secondary analysis of the previously reported GO-RAISE study that evaluated golimumab in AS patients – also showed that changes in the JSEQ scores during the course of the study significantly correlated with changes from baseline on Short Form–36 Health Survey summary scores, Bath AS Functional Index scores, Bath AS Disease Activity Index, inflammation assessments, and total and night back-pain scores.

Improvements in the night back-pain scores were the strongest predictor of improvement in sleep disturbance as measured by JSEQ scores. This finding is consistent with those from prior studies showing that sleep disturbance is predicted by pain at bedtime and during the night, the investigators noted.

Golimumab (Simponi) has Food and Drug Administration approval for treatment – with methotrexate – of moderately to severely active rheumatoid arthritis in adults; in the treatment of active psoriatic arthritis, in which it can be given with or without methotrexate; and in the treatment of active ankylosing spondylitis.

The European Medicines Agency has approved the use of golimumab for treatment of moderate to severe active RA in combination with methotrexate in patients who have not responded adequately to other treatments, including methotrexate. EMEA has also approved golimumab for the treatment of active and progressive psoriatic arthritis in patients who have not responded adequately to other treatments; it can be used alone or in combination with methotrexate. Finally, EMEA has approved it to treat severely active ankylosing spondylitis. Golimumab is used in patients who have not responded adequately to other treatments.

This study was funded by Centocor Research and Development and the Schering-Plough Research Institute. Dr. Deodhar disclosed that he has received payments from, and served on the advisory board for Centocor. Other authors on the study disclosed receiving consultancy fees, speaking fees, and/or honoraria from Centocor, Schering-Plough, Wyeth , Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Chugai, Pfizer, MSD, and/or Sanofi-Aventis, and/or owning stock or options in Johnson & Johnson.