Bruce Jancin

ORLANDO – Effective oral therapy has been at the top of the wish list of many multiple sclerosis patients for a long time – and now, seemingly all of a sudden, three approved oral agents are available to choose from.

For patients, the obvious attractions of oral therapy are ease of administration and that it’s less of a reminder that they have a serious chronic illness. But which agent is the right fit for a given patient?

All three oral drugs – fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) – are "definitely" suitable as first-line therapy in selected newly diagnosed MS patients, Dr. Mariko Kita asserted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

But the three oral drugs are not interchangeable. Each has a different mechanism of action and its own side effect profile, emphasized Dr. Kita, director of the Virginia Mason MS Center, Seattle, and director of the MS clinical trials unit at Virginia Mason’s Benaroya Research Institute.

Today few neurologists – certainly less than 10% – are using any oral agent as first-line therapy. That’s in part due to cost and reimbursement issues, but to a much greater extent it’s because most physicians don’t yet feel comfortable that the safety profiles of the oral agents are fully known. The drugs are still too new, in the eyes of most practitioners. After all, both natalizumab (Tysabri) – considered the most effective of the injectable agents – and fingolimod – the first oral agent to receive marketing approval, back in October 2010 – had to have revisionary cautions added to their labeling shortly after they were introduced.

But provider experience with the orals is expected to grow quickly. And absent any late bombshells regarding side effects, it’s widely anticipated that the use of oral agents for MS will surge within the next few years, with a corresponding decline in popularity of injectable therapies.

Demand for oral therapy will be high all across the patient spectrum: in newly diagnosed patients, in individuals with a lengthy disease history who have tried all the available disease-modifying therapies with less than satisfactory results and have been awaiting something new, in patients intolerant to or experiencing breakthrough disease on a first-line injectable agent, as well as in patients who are stable on their current injectable disease-modifying therapy but are experiencing injection fatigue or growing more concerned about their parenteral therapy’s long-term risks, Dr. Kita predicted.

Choosing between the oral options appropriately requires a focus on patient-specific factors, including comorbid conditions, reproductive status, and consideration of how the oral drug will fit in to the big picture of a long-term, staged therapy plan, she added.

Here’s her personal clinical rundown on the approved oral drugs:

• Fingolimod: This is a drug best reserved for MS patients who are otherwise relatively healthy, in Dr. Kita’s view. Specifically, it’s a less favorable option for patients with diabetes, smokers, and others with reduced pulmonary function, and in individuals at increased risk of infection, including those with a high Expanded Disability Status Scale score.

Fingolimod is a sphingosine-1-phosphate agonist. It sequesters lymphocytes in the lymph nodes so they can’t participate in autoimmune activity. The required testing prior to starting the drug, the need for careful observation during the first dose, and the necessary ongoing monitoring as long as the patient is on fingolimod make this a labor-intensive drug.

Bearing those caveats in mind, she continued, fingolimod is "reasonable" to use as a first-line agent, or as a second-line agent in the setting of intolerance to or breakthrough disease while on prior therapy.

"But I would caution those who are reserving these oral agents as second-line that we need to think about what we can reasonably expect from them. If we’re moving to them as second-line because of tolerability issues with first-line agents, yes, I think that’s most reasonable. But if we’re moving because of breakthrough disease, our experience with these agents in cases of failure with standard first-line therapies is very, very limited. Sure, the differing mechanism of action offers a reasonable alternative option, but the expectation that the oral will be better than a failed injectable has not yet been proven," Dr. Kita said.

• Teriflunomide: This is the active metabolite of leflunomide, a treatment approved by the Food and Drug Administration for rheumatoid arthritis. It was approved for treating relapsing forms of MS last fall. Teriflunomide nonselectively inhibits rapidly dividing cell populations by curbing pyrimidine synthesis via bonding to the enzyme dihydroorotate dehydrogenase.

Who’s the right fit for teriflunomide? Because the drug is rated category X and has teratogenicity potential in both men and women, it’s a given that the candidate must be on effective contraception. Also, the patient should definitely not have comorbid liver disease. And in Dr. Kita’s view, an appropriate candidate for teriflunomide has mild MS. Otherwise, the physician can get backed into a corner. That’s because the drug is excreted very slowly and is not dialyzable. Indeed, it takes 8-24 months after drug discontinuation for plasma levels to become undetectable.

"Teriflunomide could definitely be used as first-line therapy. It can be used second-line in a patient intolerant to a prior agent. But I think the long half-life complicates its use as second-line therapy in patients who’ve had breakthrough disease on prior agents, because if we need to consider a switch from teriflunomide, that long half-life has to be taken into consideration. You’ll need to consider the elimination protocol," she advised.

Patients find the elimination protocol arduous. It entails swallowing 8 g of oral cholestyramine every 8 hours for 11 days, or 50 g of activated charcoal given orally every 12 hours for 11 days.

• Dimethyl fumarate: This twice-daily oral agent, which was approved last March, activates the nuclear factor transcriptional pathway, thereby defending against oxidative stress–induced neuronal death. Dimethyl fumarate also supports myelin integrity in the central nervous system.

The drug’s side effect profile, consisting mostly of short-term flushing and gastrointestinal complaints, is the most benign of the three oral agents. Thus, it could potentially see broader use both as a first-line drug in newly diagnosed patients and as second-line therapy in patients intolerant to or experiencing disease breakthrough on other agents.

That being said, it’s still unclear whether any of the available oral agents is the best choice after natalizumab discontinuation. A couple of studies of fingolimod showed a high relapse rate in this situation, and there are simply no data as yet on the two newer agents, according to Dr. Kita.

• Upcoming oral agents: The investigational oral agent furthest along in the developmental pipeline is laquinimod, a quinolone-3-carboxamide small molecule that has completed two phase III clinical trials and is now under review by the European Medicines Agency for possible marketing approval. Teva has not yet applied to the Food and Drug Administration for U.S. approval.

Several second-generation sphingosine-1-phosphate agonists are in development. They are believed to act more selectively and thus pose fewer potential immunocompromise issues than fingolimod. These include siponimod, ponesimod, and ONO-4641.

Dr. Kita reported receiving research support from Biogen Idec (which markets Tecfidera), Novartis (which markets Gilenya and is developing siponimod), Serono, and Acorda, as well as personal compensation from Biogen Idec, Bayer, and Genzyme (which markets Aubagio).

bjancin@frontlinemedcom.com

ORLANDO – Effective oral therapy has been at the top of the wish list of many multiple sclerosis patients for a long time – and now, seemingly all of a sudden, three approved oral agents are available to choose from.

For patients, the obvious attractions of oral therapy are ease of administration and that it’s less of a reminder that they have a serious chronic illness. But which agent is the right fit for a given patient?

All three oral drugs – fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) – are "definitely" suitable as first-line therapy in selected newly diagnosed MS patients, Dr. Mariko Kita asserted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

But the three oral drugs are not interchangeable. Each has a different mechanism of action and its own side effect profile, emphasized Dr. Kita, director of the Virginia Mason MS Center, Seattle, and director of the MS clinical trials unit at Virginia Mason’s Benaroya Research Institute.

Today few neurologists – certainly less than 10% – are using any oral agent as first-line therapy. That’s in part due to cost and reimbursement issues, but to a much greater extent it’s because most physicians don’t yet feel comfortable that the safety profiles of the oral agents are fully known. The drugs are still too new, in the eyes of most practitioners. After all, both natalizumab (Tysabri) – considered the most effective of the injectable agents – and fingolimod – the first oral agent to receive marketing approval, back in October 2010 – had to have revisionary cautions added to their labeling shortly after they were introduced.

But provider experience with the orals is expected to grow quickly. And absent any late bombshells regarding side effects, it’s widely anticipated that the use of oral agents for MS will surge within the next few years, with a corresponding decline in popularity of injectable therapies.

Demand for oral therapy will be high all across the patient spectrum: in newly diagnosed patients, in individuals with a lengthy disease history who have tried all the available disease-modifying therapies with less than satisfactory results and have been awaiting something new, in patients intolerant to or experiencing breakthrough disease on a first-line injectable agent, as well as in patients who are stable on their current injectable disease-modifying therapy but are experiencing injection fatigue or growing more concerned about their parenteral therapy’s long-term risks, Dr. Kita predicted.

Choosing between the oral options appropriately requires a focus on patient-specific factors, including comorbid conditions, reproductive status, and consideration of how the oral drug will fit in to the big picture of a long-term, staged therapy plan, she added.

Here’s her personal clinical rundown on the approved oral drugs:

• Fingolimod: This is a drug best reserved for MS patients who are otherwise relatively healthy, in Dr. Kita’s view. Specifically, it’s a less favorable option for patients with diabetes, smokers, and others with reduced pulmonary function, and in individuals at increased risk of infection, including those with a high Expanded Disability Status Scale score.

Fingolimod is a sphingosine-1-phosphate agonist. It sequesters lymphocytes in the lymph nodes so they can’t participate in autoimmune activity. The required testing prior to starting the drug, the need for careful observation during the first dose, and the necessary ongoing monitoring as long as the patient is on fingolimod make this a labor-intensive drug.

Bearing those caveats in mind, she continued, fingolimod is "reasonable" to use as a first-line agent, or as a second-line agent in the setting of intolerance to or breakthrough disease while on prior therapy.

"But I would caution those who are reserving these oral agents as second-line that we need to think about what we can reasonably expect from them. If we’re moving to them as second-line because of tolerability issues with first-line agents, yes, I think that’s most reasonable. But if we’re moving because of breakthrough disease, our experience with these agents in cases of failure with standard first-line therapies is very, very limited. Sure, the differing mechanism of action offers a reasonable alternative option, but the expectation that the oral will be better than a failed injectable has not yet been proven," Dr. Kita said.

• Teriflunomide: This is the active metabolite of leflunomide, a treatment approved by the Food and Drug Administration for rheumatoid arthritis. It was approved for treating relapsing forms of MS last fall. Teriflunomide nonselectively inhibits rapidly dividing cell populations by curbing pyrimidine synthesis via bonding to the enzyme dihydroorotate dehydrogenase.

Who’s the right fit for teriflunomide? Because the drug is rated category X and has teratogenicity potential in both men and women, it’s a given that the candidate must be on effective contraception. Also, the patient should definitely not have comorbid liver disease. And in Dr. Kita’s view, an appropriate candidate for teriflunomide has mild MS. Otherwise, the physician can get backed into a corner. That’s because the drug is excreted very slowly and is not dialyzable. Indeed, it takes 8-24 months after drug discontinuation for plasma levels to become undetectable.

"Teriflunomide could definitely be used as first-line therapy. It can be used second-line in a patient intolerant to a prior agent. But I think the long half-life complicates its use as second-line therapy in patients who’ve had breakthrough disease on prior agents, because if we need to consider a switch from teriflunomide, that long half-life has to be taken into consideration. You’ll need to consider the elimination protocol," she advised.

Patients find the elimination protocol arduous. It entails swallowing 8 g of oral cholestyramine every 8 hours for 11 days, or 50 g of activated charcoal given orally every 12 hours for 11 days.

• Dimethyl fumarate: This twice-daily oral agent, which was approved last March, activates the nuclear factor transcriptional pathway, thereby defending against oxidative stress–induced neuronal death. Dimethyl fumarate also supports myelin integrity in the central nervous system.

The drug’s side effect profile, consisting mostly of short-term flushing and gastrointestinal complaints, is the most benign of the three oral agents. Thus, it could potentially see broader use both as a first-line drug in newly diagnosed patients and as second-line therapy in patients intolerant to or experiencing disease breakthrough on other agents.

That being said, it’s still unclear whether any of the available oral agents is the best choice after natalizumab discontinuation. A couple of studies of fingolimod showed a high relapse rate in this situation, and there are simply no data as yet on the two newer agents, according to Dr. Kita.

• Upcoming oral agents: The investigational oral agent furthest along in the developmental pipeline is laquinimod, a quinolone-3-carboxamide small molecule that has completed two phase III clinical trials and is now under review by the European Medicines Agency for possible marketing approval. Teva has not yet applied to the Food and Drug Administration for U.S. approval.

Several second-generation sphingosine-1-phosphate agonists are in development. They are believed to act more selectively and thus pose fewer potential immunocompromise issues than fingolimod. These include siponimod, ponesimod, and ONO-4641.

Dr. Kita reported receiving research support from Biogen Idec (which markets Tecfidera), Novartis (which markets Gilenya and is developing siponimod), Serono, and Acorda, as well as personal compensation from Biogen Idec, Bayer, and Genzyme (which markets Aubagio).

bjancin@frontlinemedcom.com

ORLANDO – Effective oral therapy has been at the top of the wish list of many multiple sclerosis patients for a long time – and now, seemingly all of a sudden, three approved oral agents are available to choose from.

For patients, the obvious attractions of oral therapy are ease of administration and that it’s less of a reminder that they have a serious chronic illness. But which agent is the right fit for a given patient?

All three oral drugs – fingolimod (Gilenya), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera) – are "definitely" suitable as first-line therapy in selected newly diagnosed MS patients, Dr. Mariko Kita asserted at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

But the three oral drugs are not interchangeable. Each has a different mechanism of action and its own side effect profile, emphasized Dr. Kita, director of the Virginia Mason MS Center, Seattle, and director of the MS clinical trials unit at Virginia Mason’s Benaroya Research Institute.

Today few neurologists – certainly less than 10% – are using any oral agent as first-line therapy. That’s in part due to cost and reimbursement issues, but to a much greater extent it’s because most physicians don’t yet feel comfortable that the safety profiles of the oral agents are fully known. The drugs are still too new, in the eyes of most practitioners. After all, both natalizumab (Tysabri) – considered the most effective of the injectable agents – and fingolimod – the first oral agent to receive marketing approval, back in October 2010 – had to have revisionary cautions added to their labeling shortly after they were introduced.

But provider experience with the orals is expected to grow quickly. And absent any late bombshells regarding side effects, it’s widely anticipated that the use of oral agents for MS will surge within the next few years, with a corresponding decline in popularity of injectable therapies.

Demand for oral therapy will be high all across the patient spectrum: in newly diagnosed patients, in individuals with a lengthy disease history who have tried all the available disease-modifying therapies with less than satisfactory results and have been awaiting something new, in patients intolerant to or experiencing breakthrough disease on a first-line injectable agent, as well as in patients who are stable on their current injectable disease-modifying therapy but are experiencing injection fatigue or growing more concerned about their parenteral therapy’s long-term risks, Dr. Kita predicted.

Choosing between the oral options appropriately requires a focus on patient-specific factors, including comorbid conditions, reproductive status, and consideration of how the oral drug will fit in to the big picture of a long-term, staged therapy plan, she added.

Here’s her personal clinical rundown on the approved oral drugs:

• Fingolimod: This is a drug best reserved for MS patients who are otherwise relatively healthy, in Dr. Kita’s view. Specifically, it’s a less favorable option for patients with diabetes, smokers, and others with reduced pulmonary function, and in individuals at increased risk of infection, including those with a high Expanded Disability Status Scale score.

Fingolimod is a sphingosine-1-phosphate agonist. It sequesters lymphocytes in the lymph nodes so they can’t participate in autoimmune activity. The required testing prior to starting the drug, the need for careful observation during the first dose, and the necessary ongoing monitoring as long as the patient is on fingolimod make this a labor-intensive drug.

Bearing those caveats in mind, she continued, fingolimod is "reasonable" to use as a first-line agent, or as a second-line agent in the setting of intolerance to or breakthrough disease while on prior therapy.

"But I would caution those who are reserving these oral agents as second-line that we need to think about what we can reasonably expect from them. If we’re moving to them as second-line because of tolerability issues with first-line agents, yes, I think that’s most reasonable. But if we’re moving because of breakthrough disease, our experience with these agents in cases of failure with standard first-line therapies is very, very limited. Sure, the differing mechanism of action offers a reasonable alternative option, but the expectation that the oral will be better than a failed injectable has not yet been proven," Dr. Kita said.

• Teriflunomide: This is the active metabolite of leflunomide, a treatment approved by the Food and Drug Administration for rheumatoid arthritis. It was approved for treating relapsing forms of MS last fall. Teriflunomide nonselectively inhibits rapidly dividing cell populations by curbing pyrimidine synthesis via bonding to the enzyme dihydroorotate dehydrogenase.

Who’s the right fit for teriflunomide? Because the drug is rated category X and has teratogenicity potential in both men and women, it’s a given that the candidate must be on effective contraception. Also, the patient should definitely not have comorbid liver disease. And in Dr. Kita’s view, an appropriate candidate for teriflunomide has mild MS. Otherwise, the physician can get backed into a corner. That’s because the drug is excreted very slowly and is not dialyzable. Indeed, it takes 8-24 months after drug discontinuation for plasma levels to become undetectable.

"Teriflunomide could definitely be used as first-line therapy. It can be used second-line in a patient intolerant to a prior agent. But I think the long half-life complicates its use as second-line therapy in patients who’ve had breakthrough disease on prior agents, because if we need to consider a switch from teriflunomide, that long half-life has to be taken into consideration. You’ll need to consider the elimination protocol," she advised.

Patients find the elimination protocol arduous. It entails swallowing 8 g of oral cholestyramine every 8 hours for 11 days, or 50 g of activated charcoal given orally every 12 hours for 11 days.

• Dimethyl fumarate: This twice-daily oral agent, which was approved last March, activates the nuclear factor transcriptional pathway, thereby defending against oxidative stress–induced neuronal death. Dimethyl fumarate also supports myelin integrity in the central nervous system.

The drug’s side effect profile, consisting mostly of short-term flushing and gastrointestinal complaints, is the most benign of the three oral agents. Thus, it could potentially see broader use both as a first-line drug in newly diagnosed patients and as second-line therapy in patients intolerant to or experiencing disease breakthrough on other agents.

That being said, it’s still unclear whether any of the available oral agents is the best choice after natalizumab discontinuation. A couple of studies of fingolimod showed a high relapse rate in this situation, and there are simply no data as yet on the two newer agents, according to Dr. Kita.

• Upcoming oral agents: The investigational oral agent furthest along in the developmental pipeline is laquinimod, a quinolone-3-carboxamide small molecule that has completed two phase III clinical trials and is now under review by the European Medicines Agency for possible marketing approval. Teva has not yet applied to the Food and Drug Administration for U.S. approval.

Several second-generation sphingosine-1-phosphate agonists are in development. They are believed to act more selectively and thus pose fewer potential immunocompromise issues than fingolimod. These include siponimod, ponesimod, and ONO-4641.

Dr. Kita reported receiving research support from Biogen Idec (which markets Tecfidera), Novartis (which markets Gilenya and is developing siponimod), Serono, and Acorda, as well as personal compensation from Biogen Idec, Bayer, and Genzyme (which markets Aubagio).

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – Diabetes mellitus, osteoporosis, and hypertension are conditions that should boost the index of suspicion that a patient with some cushingoid features may in fact have endogenous Cushing’s syndrome, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

An estimated 1 in 20 patients with type 2 diabetes has endogenous Cushing’s syndrome. The prevalence of this form of hypercortisolism is even greater – estimated at up to 11% – among individuals with osteoporosis. In hypertensive patients, the figure is 1%. And among patients with an incidentally detected adrenal mass, it’s 6%-9%, according to Dr. McDermott, professor of medicine and director of endocrinology and diabetes at the University of Colorado.

"Endogenous Cushing’s syndrome is not rare. I suspect I’ve seen more cases than I’ve diagnosed," he observed. "I’ve probably missed a lot because I failed to screen people, not recognizing that they had cushingoid features. Not everyone looks classic."

There are three screening tests for endogenous Cushing’s syndrome that all primary care physicians ought to be familiar with: the 24-hour urine cortisol test, the bedtime salivary cortisol test, and the overnight 1-mg dexamethasone suppression test.

"I think if you have moderate or mild suspicion, you should use one of these tests. If you have more than moderate suspicion – if a patient really looks like he or she has Cushing’s syndrome – then I would use at least two screening tests to rule out endogenous Cushing’s syndrome," the endocrinologist continued.

The patient performs the bedtime salivary cortisol test at home, obtaining samples two nights in a row and mailing them to an outside laboratory. The overnight dexamethasone suppression test entails taking 1 mg of dexamethasone at bedtime, then measuring serum cortisol the next morning. A value greater than 1.8 mcg/dL is a positive result.

Pregnant women constitute a special population for whom the screening method recommended in Endocrine Society clinical practice guidelines (J. Clin. Endocrinol. Metab. 2008;93:1526-40) is the 24-hour urine cortisol test. That’s because pregnancy is a state featuring high levels of cortisol-binding globulins, which invalidates the other tests. In patients with renal failure, the recommended screening test is the 1-mg dexamethasone suppression test. In patients on antiepileptic drugs, the 24-hour urine cortisol or bedtime salivary cortisol test is advised, because antiseizure medications enhance the metabolism of dexamethasone.

Dr. McDermott said that "by far" the most discriminatory clinical features of endogenous Cushing’s syndrome are easy bruising, violaceous striae on the trunk, facial plethora, and proximal muscle weakness.

"They’re by no means specific. You’ll see these features in people who don’t have Cushing’s syndrome. But those are the four things that should make you really consider Cushing’s syndrome in your differential diagnosis," he stressed.

More widely recognized yet actually less discriminatory clinical features include facial fullness and the "buffalo hump," supraclavicular fullness, central obesity, hirsutism, reduced libido, edema, and thin or poorly healing skin.

Endogenous Cushing’s syndrome can have three causes. An adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma accounts for 80% of cases. A cortisol-secreting adrenal tumor is the cause of 10%. And another 10% are due to an ectopic ACTH-secreting tumor, most commonly a bronchial carcinoid tumor.

Once the primary care physician has a positive screening test in hand, it’s typical to refer the affected patient to an endocrinologist in order to differentiate which of the three causes is present. This is accomplished based upon the results of a large, 8-mg dexamethasone suppression test coupled with measurement of plasma ACTH levels.

Dr. McDermott recommended as a good read on the topic of evaluating a patient with endogenous Cushing’s syndrome a recent review article that included a useful algorithm (N. Engl. J. Med. 2013;368:2126-36).

He reported having no financial conflicts.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – The era of selective screening for hepatitis C infection based upon risk factors such as alcoholism or a history of illicit drug use or incarceration has come to an end.

The June 2013 U.S Preventive Services Task Force Grade B recommendation for one-time testing of all baby boomers for hepatitis C infection means that the birth cohort–based testing will be a covered benefit under the Affordable Care Act, Dr. Gregory T. Everson noted at a conference on internal medicine sponsored by the University of Colorado.

The task force’s action was an endorsement of an earlier Centers for Disease Control and Prevention recommendation that all adults born in 1945-1965 should receive one-time testing for HCV without prior assessment of HCV risk (MMWR Recomm. Rep. 2012;61(RR-4):1-32). This is sound policy for several reasons, said Dr. Everson, professor of medicine and director of hepatology at the University of Colorado, Denver.

First, baby boomers account for roughly 75% of all cases of chronic hepatitis C virus (HCV) infection in the United States. Most of these cases remain undiagnosed. The CDC estimates that one-time universal testing of baby boomers would identify 800,000 new cases and prevent more than 120,000 deaths. The prevalence of HCV in the United States isn’t expected to peak until the year 2020.

In addition, recent dramatic advances in the treatment of chronic HCV make it likely that the therapy will move from hepatology clinics to primary care physicians’ offices, where preventive medicine is a priority, Dr. Everson noted.

The screening entails a blood test for HCV antibody. If the results are positive, the next step is to confirm the diagnosis via a polymerase chain reaction–based test for HCV RNA quantification. There is roughly a 75% chance that an HCV antibody–positive patient will be HCV RNA positive, which indicates the patient has a chronic HCV infection. The natural history of HCV infection is roughly a 30-year timeline from acute infection to liver transplantation or death.

Dr. Everson said that for assessing the severity of hepatic fibrosis in patients with HCV, he still relies heavily on liver biopsy, which most experts consider the gold standard.

The Food and Drug Administration has approved ultrasound-based transient elastography via the FibroScan device as a noninvasive alternative. The device, which costs about $130,000, is good at identifying cirrhosis but less accurate in staging intermediate levels of fibrosis, Dr. Everson noted. The same is true of an FDA-approved serologic test for fibrosis, he said.

Dr. Everson is involved in developing new treatments for HCV. He reported that he receives research grants from, serves as a consultant to, or serves as an advisory board member for roughly two dozen pharmaceutical companies.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – The era of selective screening for hepatitis C infection based upon risk factors such as alcoholism or a history of illicit drug use or incarceration has come to an end.

The June 2013 U.S Preventive Services Task Force Grade B recommendation for one-time testing of all baby boomers for hepatitis C infection means that the birth cohort–based testing will be a covered benefit under the Affordable Care Act, Dr. Gregory T. Everson noted at a conference on internal medicine sponsored by the University of Colorado.

The task force’s action was an endorsement of an earlier Centers for Disease Control and Prevention recommendation that all adults born in 1945-1965 should receive one-time testing for HCV without prior assessment of HCV risk (MMWR Recomm. Rep. 2012;61(RR-4):1-32). This is sound policy for several reasons, said Dr. Everson, professor of medicine and director of hepatology at the University of Colorado, Denver.

First, baby boomers account for roughly 75% of all cases of chronic hepatitis C virus (HCV) infection in the United States. Most of these cases remain undiagnosed. The CDC estimates that one-time universal testing of baby boomers would identify 800,000 new cases and prevent more than 120,000 deaths. The prevalence of HCV in the United States isn’t expected to peak until the year 2020.

In addition, recent dramatic advances in the treatment of chronic HCV make it likely that the therapy will move from hepatology clinics to primary care physicians’ offices, where preventive medicine is a priority, Dr. Everson noted.

The screening entails a blood test for HCV antibody. If the results are positive, the next step is to confirm the diagnosis via a polymerase chain reaction–based test for HCV RNA quantification. There is roughly a 75% chance that an HCV antibody–positive patient will be HCV RNA positive, which indicates the patient has a chronic HCV infection. The natural history of HCV infection is roughly a 30-year timeline from acute infection to liver transplantation or death.

Dr. Everson said that for assessing the severity of hepatic fibrosis in patients with HCV, he still relies heavily on liver biopsy, which most experts consider the gold standard.

The Food and Drug Administration has approved ultrasound-based transient elastography via the FibroScan device as a noninvasive alternative. The device, which costs about $130,000, is good at identifying cirrhosis but less accurate in staging intermediate levels of fibrosis, Dr. Everson noted. The same is true of an FDA-approved serologic test for fibrosis, he said.

Dr. Everson is involved in developing new treatments for HCV. He reported that he receives research grants from, serves as a consultant to, or serves as an advisory board member for roughly two dozen pharmaceutical companies.

bjancin@frontlinemedcom.com

ESTES PARK, COLO. – The era of selective screening for hepatitis C infection based upon risk factors such as alcoholism or a history of illicit drug use or incarceration has come to an end.

The June 2013 U.S Preventive Services Task Force Grade B recommendation for one-time testing of all baby boomers for hepatitis C infection means that the birth cohort–based testing will be a covered benefit under the Affordable Care Act, Dr. Gregory T. Everson noted at a conference on internal medicine sponsored by the University of Colorado.

The task force’s action was an endorsement of an earlier Centers for Disease Control and Prevention recommendation that all adults born in 1945-1965 should receive one-time testing for HCV without prior assessment of HCV risk (MMWR Recomm. Rep. 2012;61(RR-4):1-32). This is sound policy for several reasons, said Dr. Everson, professor of medicine and director of hepatology at the University of Colorado, Denver.

First, baby boomers account for roughly 75% of all cases of chronic hepatitis C virus (HCV) infection in the United States. Most of these cases remain undiagnosed. The CDC estimates that one-time universal testing of baby boomers would identify 800,000 new cases and prevent more than 120,000 deaths. The prevalence of HCV in the United States isn’t expected to peak until the year 2020.

In addition, recent dramatic advances in the treatment of chronic HCV make it likely that the therapy will move from hepatology clinics to primary care physicians’ offices, where preventive medicine is a priority, Dr. Everson noted.

The screening entails a blood test for HCV antibody. If the results are positive, the next step is to confirm the diagnosis via a polymerase chain reaction–based test for HCV RNA quantification. There is roughly a 75% chance that an HCV antibody–positive patient will be HCV RNA positive, which indicates the patient has a chronic HCV infection. The natural history of HCV infection is roughly a 30-year timeline from acute infection to liver transplantation or death.

Dr. Everson said that for assessing the severity of hepatic fibrosis in patients with HCV, he still relies heavily on liver biopsy, which most experts consider the gold standard.

The Food and Drug Administration has approved ultrasound-based transient elastography via the FibroScan device as a noninvasive alternative. The device, which costs about $130,000, is good at identifying cirrhosis but less accurate in staging intermediate levels of fibrosis, Dr. Everson noted. The same is true of an FDA-approved serologic test for fibrosis, he said.

Dr. Everson is involved in developing new treatments for HCV. He reported that he receives research grants from, serves as a consultant to, or serves as an advisory board member for roughly two dozen pharmaceutical companies.

bjancin@frontlinemedcom.com

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

bjancin@frontlinemedcom.com

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

bjancin@frontlinemedcom.com

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

bjancin@frontlinemedcom.com

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

bjancin@frontlinemedcom.com

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

bjancin@frontlinemedcom.com

CHICAGO – Only 31% of patients with type 2 diabetes who were placed on a glucagonlike peptide-1 agonist persisted on the medication for at least 6 months in a very large national retrospective cohort study.

That’s significantly lower than the 39% rate of 6-month treatment persistence in patients placed on a dipeptidyl-peptidase-4 inhibitor, Carol E. Koro, Ph.D., reported at the annual scientific sessions of the American Diabetes Association.

The 12-month treatment discontinuation rate was 89% in patients placed on a GLP-1 agonist, compared with 82% for patients on a DPP-4 inhibitor and 84% among those placed on other antidiabetic agents, added Dr. Koro, an epidemiologist at GlaxoSmithKline in Research Triangle Park, N.C.

She presented a retrospective study examining treatment utilization patterns among 134,696 commercially insured type 2 diabetes patients placed on a GLP-1 agonist, 202,269 given a DPP-4 inhibitor, and 1,014,630 on other antidiabetic agents. The data source was the Truven Health Analytics MarketScan database for 2005-2011.

Nonadherence was defined by a prescription refill pattern indicating that less than 80% of a prescribed medication was being taken. The nonadherence rate was 9.6% in patients whose physicians prescribed a GLP-1 agonist, 5.4% in those placed on a DPP-4 inhibitor, and 4.4% in patients on other antidiabetic agents.

The median time to treatment discontinuation was 90 days in the GLP-1 agonist cohort, 120 days for the DPP-4 inhibitor cohort, and 90 days for patients assigned to other antidiabetic agents. The mean time to discontinuation was 178 days for the GLP-1 agonist group, 226 days for the DPP-4 inhibitor cohort, and 196 days for the group on other antidiabetic medications.

This was not a randomized trial, and the GLP-1 agonist cohort differed from the other two groups in important ways.

For example, they were more likely to be female: 57% of the GLP-1 agonist cohort were women, compared with 44% in the DPP-4 inhibitor cohort and 47% of patients on other antidiabetic agents. The GLP-1 agonist group also had a greater prevalence of obesity: 12%, compared with 8% in the DPP-4 inhibitor cohort and a similar figure among those on other antidiabetic agents. In addition, the GLP-1 agonist cohort had a higher baseline prevalence of microvascular complications.

Only 8% of patients placed on a GLP-1 agonist initiated the drug as new therapy; 78% started it as add-on therapy. In contrast, 17% of patients initiated a DPP-4 inhibitor as new therapy, while 59% employed the drug as add-on therapy.

The subgroup of the GLP-1 agonist cohort who initiated the drug as an add-on to basal insulin had a higher baseline prevalence of microvascular complications and greater use of antilipidemic drugs, antihypertensive agents, and antiplatelet agents than did those using the drug as an add-on to oral antidiabetic therapy. Nevertheless, the 6-month treatment persistence rates in the two subgroups were nearly identical.

The take-away message from this study is clear, Dr. Koro said: "These results demonstrate the need for improved persistence with GLP-1 agonist treatment."

She noted that other investigators have estimated that reducing the rate of nonadherence to antidiabetes medications could avoid 700,000 emergency department visits and 341,000 hospitalizations annually, with a resultant $4.7 billion annual savings in health care costs (Health Aff. [Millwood] 2012;31:1836-46).

GlaxoSmithKline funded Dr. Koro’s study. The company’s investigational GLP-1 agonist albiglutide is under review by the Food and Drug Administration.

bjancin@frontlinemedcom.com

HOLLYWOOD, FLA. – An immediate and abrupt switch to iloperidone from another atypical antipsychotic agent provides a markedly greater clinical response rate within the first 2 weeks than does a gradual switch with stepwise dose reduction of the drug being discontinued, according to data from the i-FANS trial.

This superior early clinical response rate comes at the price of a modest increase in dizziness. However, the rates of no other antipsychotic side effects in the Iloperidone Flexible-Dose Study Assessing Efficacy and Tolerability of Two Switch Approaches in Schizophrenia patients, or i-FANS trial, were affected by switching strategy, Dr. Leslie Citrome reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The i-FANS study was a multicenter, open-label trial involving 500 adults with schizophrenia randomized to a gradual or immediate switch from risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) to iloperidone (Fanapt). The switch was made because of inadequate efficacy and/or emergence of tolerability problems with the drug being discontinued.

In the gradual-switch group, the baseline dose of the first antipsychotic was reduced by 50% on day 1 and by 75% after 1 week, with a complete halt of the drug at the end of week 2. In contrast, current therapy was discontinued on day 0 in the immediate-switch group. Patients in both study arms received iloperidone at 1 mg b.i.d. on day 1, titrated over 4 days to 6 mg b.i.d., then further increasing by no more than 4 mg per day up to 12 mg b.i.d. as warranted, explained Dr. Citrome, professor of psychiatry at New York Medical College, Valhalla.

The primary outcome for this analysis was a rating of "much" or "very much" improved on the Integrated Clinical Global Impression of Change (I-CGI-C) at the end of week 2. This endpoint was achieved in 5.4% of the gradual switch and 11.1% of the immediate switch group at week 1, and by 17.5% and 26.1%, respectively, in the two groups at week 2. The significant advantage favoring the immediate switch strategy was similar in magnitude across the individual subgroups switching from risperidone, olanzapine, and aripiprazole.

The most common treatment emergent adverse event seen in i-FANS was dizziness. The incidence was significantly lower in the gradual-switch group during week 1, at 8.8% compared to 14.2% in the immediate-switch group. The rate during week 2 was 1.3% in the gradual- and 3.2% in the immediate switch group during week 2.

Iloperidone is a mixed dopamine D2, serotonin 5HT-2A, and alpha-adrenergic antagonist approved for the treatment of schizophrenia.

The i-FANS study was supported by Novartis. Dr. Citrome reported receiving research support and/or consulting fees from Novartis and 17 other pharmaceutical companies.

bjancin@frontlinemedcom.com

HOLLYWOOD, FLA. – An immediate and abrupt switch to iloperidone from another atypical antipsychotic agent provides a markedly greater clinical response rate within the first 2 weeks than does a gradual switch with stepwise dose reduction of the drug being discontinued, according to data from the i-FANS trial.

This superior early clinical response rate comes at the price of a modest increase in dizziness. However, the rates of no other antipsychotic side effects in the Iloperidone Flexible-Dose Study Assessing Efficacy and Tolerability of Two Switch Approaches in Schizophrenia patients, or i-FANS trial, were affected by switching strategy, Dr. Leslie Citrome reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The i-FANS study was a multicenter, open-label trial involving 500 adults with schizophrenia randomized to a gradual or immediate switch from risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) to iloperidone (Fanapt). The switch was made because of inadequate efficacy and/or emergence of tolerability problems with the drug being discontinued.

In the gradual-switch group, the baseline dose of the first antipsychotic was reduced by 50% on day 1 and by 75% after 1 week, with a complete halt of the drug at the end of week 2. In contrast, current therapy was discontinued on day 0 in the immediate-switch group. Patients in both study arms received iloperidone at 1 mg b.i.d. on day 1, titrated over 4 days to 6 mg b.i.d., then further increasing by no more than 4 mg per day up to 12 mg b.i.d. as warranted, explained Dr. Citrome, professor of psychiatry at New York Medical College, Valhalla.

The primary outcome for this analysis was a rating of "much" or "very much" improved on the Integrated Clinical Global Impression of Change (I-CGI-C) at the end of week 2. This endpoint was achieved in 5.4% of the gradual switch and 11.1% of the immediate switch group at week 1, and by 17.5% and 26.1%, respectively, in the two groups at week 2. The significant advantage favoring the immediate switch strategy was similar in magnitude across the individual subgroups switching from risperidone, olanzapine, and aripiprazole.

The most common treatment emergent adverse event seen in i-FANS was dizziness. The incidence was significantly lower in the gradual-switch group during week 1, at 8.8% compared to 14.2% in the immediate-switch group. The rate during week 2 was 1.3% in the gradual- and 3.2% in the immediate switch group during week 2.

Iloperidone is a mixed dopamine D2, serotonin 5HT-2A, and alpha-adrenergic antagonist approved for the treatment of schizophrenia.

The i-FANS study was supported by Novartis. Dr. Citrome reported receiving research support and/or consulting fees from Novartis and 17 other pharmaceutical companies.

bjancin@frontlinemedcom.com

HOLLYWOOD, FLA. – An immediate and abrupt switch to iloperidone from another atypical antipsychotic agent provides a markedly greater clinical response rate within the first 2 weeks than does a gradual switch with stepwise dose reduction of the drug being discontinued, according to data from the i-FANS trial.

This superior early clinical response rate comes at the price of a modest increase in dizziness. However, the rates of no other antipsychotic side effects in the Iloperidone Flexible-Dose Study Assessing Efficacy and Tolerability of Two Switch Approaches in Schizophrenia patients, or i-FANS trial, were affected by switching strategy, Dr. Leslie Citrome reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The i-FANS study was a multicenter, open-label trial involving 500 adults with schizophrenia randomized to a gradual or immediate switch from risperidone (Risperdal), olanzapine (Zyprexa), or aripiprazole (Abilify) to iloperidone (Fanapt). The switch was made because of inadequate efficacy and/or emergence of tolerability problems with the drug being discontinued.

In the gradual-switch group, the baseline dose of the first antipsychotic was reduced by 50% on day 1 and by 75% after 1 week, with a complete halt of the drug at the end of week 2. In contrast, current therapy was discontinued on day 0 in the immediate-switch group. Patients in both study arms received iloperidone at 1 mg b.i.d. on day 1, titrated over 4 days to 6 mg b.i.d., then further increasing by no more than 4 mg per day up to 12 mg b.i.d. as warranted, explained Dr. Citrome, professor of psychiatry at New York Medical College, Valhalla.

The primary outcome for this analysis was a rating of "much" or "very much" improved on the Integrated Clinical Global Impression of Change (I-CGI-C) at the end of week 2. This endpoint was achieved in 5.4% of the gradual switch and 11.1% of the immediate switch group at week 1, and by 17.5% and 26.1%, respectively, in the two groups at week 2. The significant advantage favoring the immediate switch strategy was similar in magnitude across the individual subgroups switching from risperidone, olanzapine, and aripiprazole.

The most common treatment emergent adverse event seen in i-FANS was dizziness. The incidence was significantly lower in the gradual-switch group during week 1, at 8.8% compared to 14.2% in the immediate-switch group. The rate during week 2 was 1.3% in the gradual- and 3.2% in the immediate switch group during week 2.

Iloperidone is a mixed dopamine D2, serotonin 5HT-2A, and alpha-adrenergic antagonist approved for the treatment of schizophrenia.

The i-FANS study was supported by Novartis. Dr. Citrome reported receiving research support and/or consulting fees from Novartis and 17 other pharmaceutical companies.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

CHICAGO – A low-cost lifestyle intervention program designed for real-world application in obese and overweight patients achieved sustained weight loss and a reduced risk of developing diabetes in a large 3-year observational study.

The MOVE! program (Managing Overweight and/or Obesity in Veterans Everywhere) was launched in 2005 in 130 hospitals and clinics in the Department of Veterans Affairs (VA) system, the nation’s largest integrated health care system. MOVE! is based upon principles proven effective in the National Institutes of Health’s landmark Diabetes Prevention Program (DPP), an intensive diet and exercise program that achieved a sustained 34% reduction in the incidence of diabetes at 10 years.

The problem, according to Sandra L. Jackson, is that the DPP and other successful research projects use patients who volunteer to participate and thus may be particularly highly motivated.

"We know little about the results that can be achieved in real-world health care settings, where participants are patients and their health care providers recommend a change in lifestyle," she noted in presenting the MOVE! results at the annual scientific sessions of the American Diabetes Association.

That was the impetus for her study of 3-year outcomes nationally in MOVE! The results were so impressive that MOVE! was named one of the five studies selected for an encore presentation at the ADA President’s Oral Session out of the more than 2,000 studies presented at the conference.

The MOVE! program consists of 8-12 weekly group sessions focused primarily on physical activity and nutrition. More than 400,000 veterans have participated in MOVE! since 2005. They signed up for one of two reasons: either they were obese, or they were overweight with a weight-related chronic health condition, such as osteoarthritis, coronary artery disease, diabetes, or sleep apnea. At their first MOVE! session, 38% of participants were known to have diabetes.

Ms. Jackson, a PhD candidate at Emory University, Atlanta, reported on the 135,686 MOVE! participants with 3-year follow-up data, comparing their outcomes with roughly 1.5 million VA patients who were MOVE! eligible but chose not to participate.

A total of 8.7% of participants were classified as intense and sustained in their involvement with the program based upon their having attended at least eight sessions within a 6-month period, with at least 129 days between the first and last session. Everyone else was categorized as "less involved."

Among the overall group of nearly 136,000 patients, mean body mass index dropped over the course of 3 years of follow-up from 36.3 kg/m² to 35.8 kg/m², representing a 1.3% loss in body weight. The intense and sustained participants lost an average of 2.5% of their initial body weight, compared with a 1% loss in the less-involved subjects.

The active participants typically experienced virtually all of their weight loss during the first 6 months, then maintained their new body weight for the next 2.5 years.

Overall, three-quarters of the intense and sustained participants lost any weight or maintained their baseline body weight over 3 years. In contrast, two-thirds of the less-active participants did so.

Diabetes risk moves down

In a multivariate analysis adjusted for baseline BMI, age, sex, and the use of medications that affect body weight, patients who lost any weight or remained weight stable over 3 years were 16% less likely to develop new-onset diabetes than those who gained weight.

The intense and sustained MOVE! participants were significantly more likely to experience a clinically meaningful weight loss of 5%. A total of 28% of them did so, compared with 16% of the less-active participants and 11% of MOVE!-eligible nonparticipants.

MOVE! enrollees with diabetes at baseline were more likely to become intense and sustained participants than those without baseline diabetes, by a margin of 9.6% to 7.8%. Overall, patients with diabetes also lost more weight: a mean of 1.7% body weight at 3 years, compared with a 0.9% drop in nondiabetic participants.

Among the 66,933 MOVE! participants without diabetes at baseline, the 3-year incidence of diabetes was 18.7%. A progressive relationship existed between weight change and diabetes incidence. At the extremes, participants who lost at least 10% of their initial body weight had a 3-year incidence of diabetes of 15%, while those with a 10% or greater weight gain had a 22% incidence of diabetes.

In a multivariate analysis, the intense and sustained participants in MOVE! had a 33% reduction in incident diabetes over 3 years, compared with the roughly 1.5 million VA patients who were MOVE! eligible but didn’t participate.

Ms. Jackson noted that a major limitation of the MOVE! program is that less than 10% of participants are actively involved. Those are the ones who reap the greatest benefits in terms of weight loss and reduced risk of diabetes.

"We need to learn how to encourage participation," she observed.

MOVE! to more health plans?

Ms. Jackson and her coinvestigators see MOVE! as well suited for adoption by other large national health care organizations.

MOVE! differs from the DPP in several key ways. It’s shorter, with 8-12 weekly group sessions largely devoted to nutrition and physical activity, compared with 16 sessions in DPP. The MOVE! classes can be taken in any order, while the DPP program requires sessions to be done in a specific sequence. MOVE! sessions can be run by exercise physiologists, nutritionists, diabetes educators, and other professionals; DPP uses a single coach.

Also, MOVE! is less structured than the DPP in that MOVE! emphasizes individualized, patient-determined goal setting developed through motivational interviewing techniques, while the DPP features fixed, generic goals.

For example, whereas the DPP set a target of 150 minutes of moderate exercise per week, MOVE! is more inclusive. It is open to veterans for whom that exercise goal may not be achievable.

Another important difference: Eligibility for MOVE! is based upon body weight, and many participants already have diabetes. In contrast, DPP participants had to be prediabetic, Ms. Jackson noted.

Future MOVE! analyses will explore the program’s impact upon participants’ health and resource utilization.

The originality of the MOVE! program is that it allows people with or without diabetes to participate, explained session chair Dr. Elbert S. Huang of the department of medicine at the University of Chicago. In contrast, most of the classic diabetes prevention studies had very narrow entry criteria. How is it possible, he asked, for such a wide range of patients in a given class to stay on the same page in terms of goal setting?

"As a practical matter," Ms. Jackson explained, "it’s much easier for the VA system to allow all comers who are obese or overweight with a weight-related health condition to participate. The goals are individualized. The program uses the principles of motivational interviewing to ask veterans, ‘How do you want to change your life?’ "

The Department of Veterans Affairs supported the study. Ms. Jackson reported having no conflicts of interest.

bjancin@frontlinemedcom.com

ORLANDO – The randomized trials evidence supporting a positive clinical effect for medical marijuana in relieving symptoms of multiple sclerosis is strongest for improvement of pain, patient-reported spasticity, and sleep disturbances.

That’s the clear message from an analysis of the 19 published, reasonable-quality randomized trials of cannabis use in patients with MS, Dr. Allen C. Bowling reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s consistent with my personal observation in a state where we’ve had medical marijuana for 12 years and where recreational marijuana was approved in last November’s election. The most consistent effect my patients report is on nocturnal pain and/or spasticity, which is consistent with the results of the clinical trials. The patients typically use a little bit at bedtime," according to Dr. Bowling, medical director of the MS service and director of the complementary and alternative medicine service at the Colorado Neurological Institute, Englewood.

The evidence that medical marijuana is of benefit for the bladder dysfunction associated with MS is weaker: Of 9 clinical trials that included bladder dysfunction as an endpoint, 4 were positive, 5 negative.

Occupying the bottom tier in terms of evidence-based therapy are objectively measured spasticity and tremor. Of 13 clinical trials that incorporated objective, clinician-assessed spasticity as an endpoint, only 2 were positive, with 11 negative. And none of the 5 decent-quality randomized trials that examined medical marijuana for relief of tremor in MS patients was positive.

In contrast, 9 of 11 studies that looked at pain as an endpoint reported a positive effect. Of 13 studies with patient-reported spasticity as an endpoint, 9 were positive, 4 negative. And of 6 randomized trials with sleep quality as an endpoint, 5 were positive, 1 negative, noted Dr. Bowling, who is clinical professor of neurology at the University of Colorado, Denver.

Medical marijuana is now legal in 18 states and the District of Columbia.

The largest and in Dr. Bowling’s view one of the best-conducted randomized trials in the field was the multicenter U.K. CAMS trial. The 15-week study included 630 MS patients who were randomized to oral tetrahydrocannabinol (Marinol); Cannador, an oral capsule containing a standardized amount of whole-plant extract; or placebo. The investigators found no significant difference between the cannabis-based therapies and placebo in improving spasticity as objectively measured using the Ashworth score, which was the primary study endpoint. However, the two active treatment arms did show significant benefit in terms of the secondary endpoints of improvement in pain, self-reported spasticity, and sleep (Lancet 2003;362:1517-26).

Another speaker at the session on prescribing medical marijuana underscored the beneficial effect on sleep disruption.

"In every single population – whether it’s Crohn’s disease, epilepsy, HIV, noncancer pain, cancer pain – improved sleep is always one of the most robust outcomes patients report. This is something that in clinical practice we tend to push to one side. We have some medications for pain management that we sometimes use for sleep, but cannabis use at nighttime seems to be a very powerful agent to improve sleep quality," observed Dr. Mark F. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit of McGill University in Montreal.

Dr. Bowling estimated that roughly 80% of his MS patients have little or no interest in medical marijuana. Those who are using it span a spectrum ranging from patients who were recreational users of pot before their MS diagnosis and who now seek beneficial MS effects or simply a license to use it recreationally, to elderly individuals with no history of marijuana use who have found cannabis is the only thing that effectively relieves some of their symptoms.

The neurologist noted two glaring paradoxes that emerged from his review of the clinical trials literature on medical marijuana for MS. One is that only 2 of the 19 studies utilized smoked marijuana, even though it’s far and away the most readily available form of the agent for U.S. patients. The most widely studied agent nabiximols (Sativex), an extract formulated as an oral spray – is approved as a prescription drug in Canada, the United Kingdom, and other countries, but not in the United States. And while Marinol and oral nabilone (Cesamet) are approved by the Food and Drug Administration, they’re not widely prescribed.

"I find it particularly challenging to apply the medical literature in this area to clinical situations. In our clinical practice, the way it seems to work out best is for patients to experiment on their own with marijuana as a prn add-on to their spasticity and/or pain medications, especially at bedtime or, if symptoms are worse, in the afternoon. But the dose, frequency, formulation, quality control ... it’s a real challenge. It’s like there are parallel universes of care, where we’re prescribing the conventional medications, and then we find out that the patients are also using marijuana," Dr. Bowling said.

The other paradox is the huge disconnect between the generally quite favorable subjective patient self-reports of improvement in spasticity and the largely negative objective results. The explanation may lie in part in the inadequacy of the Ashworth score as an outcome measure. It has come under frequent criticism, since some approved antispasticity medications have shown only modest or no improvement in Ashworth scores. But the limitations of the Ashworth score are probably only part of the story, in Dr. Bowling’s view.

"Patients’ assessments are 24/7; ours is a brief clinical visit at a prespecified time. Also, there is a pain component to spasticity, so for some patients who feel their spasticity is improving with the use of marijuana it may just be the pain aspect of the spasticity, or a euphoric view of the world that’s changing their perception of how severe the spasticity is. But for some patients, maybe it doesn’t matter whether it’s a subjective or objective assessment that’s improving, especially for those who don’t have high physical or cognitive demands during the day," he said.

Dr. Bowling reported having no conflicts of interest. Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.

bjancin@frontlinemedcom.com

ORLANDO – The randomized trials evidence supporting a positive clinical effect for medical marijuana in relieving symptoms of multiple sclerosis is strongest for improvement of pain, patient-reported spasticity, and sleep disturbances.

That’s the clear message from an analysis of the 19 published, reasonable-quality randomized trials of cannabis use in patients with MS, Dr. Allen C. Bowling reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s consistent with my personal observation in a state where we’ve had medical marijuana for 12 years and where recreational marijuana was approved in last November’s election. The most consistent effect my patients report is on nocturnal pain and/or spasticity, which is consistent with the results of the clinical trials. The patients typically use a little bit at bedtime," according to Dr. Bowling, medical director of the MS service and director of the complementary and alternative medicine service at the Colorado Neurological Institute, Englewood.

The evidence that medical marijuana is of benefit for the bladder dysfunction associated with MS is weaker: Of 9 clinical trials that included bladder dysfunction as an endpoint, 4 were positive, 5 negative.

Occupying the bottom tier in terms of evidence-based therapy are objectively measured spasticity and tremor. Of 13 clinical trials that incorporated objective, clinician-assessed spasticity as an endpoint, only 2 were positive, with 11 negative. And none of the 5 decent-quality randomized trials that examined medical marijuana for relief of tremor in MS patients was positive.

In contrast, 9 of 11 studies that looked at pain as an endpoint reported a positive effect. Of 13 studies with patient-reported spasticity as an endpoint, 9 were positive, 4 negative. And of 6 randomized trials with sleep quality as an endpoint, 5 were positive, 1 negative, noted Dr. Bowling, who is clinical professor of neurology at the University of Colorado, Denver.

Medical marijuana is now legal in 18 states and the District of Columbia.

The largest and in Dr. Bowling’s view one of the best-conducted randomized trials in the field was the multicenter U.K. CAMS trial. The 15-week study included 630 MS patients who were randomized to oral tetrahydrocannabinol (Marinol); Cannador, an oral capsule containing a standardized amount of whole-plant extract; or placebo. The investigators found no significant difference between the cannabis-based therapies and placebo in improving spasticity as objectively measured using the Ashworth score, which was the primary study endpoint. However, the two active treatment arms did show significant benefit in terms of the secondary endpoints of improvement in pain, self-reported spasticity, and sleep (Lancet 2003;362:1517-26).

Another speaker at the session on prescribing medical marijuana underscored the beneficial effect on sleep disruption.

"In every single population – whether it’s Crohn’s disease, epilepsy, HIV, noncancer pain, cancer pain – improved sleep is always one of the most robust outcomes patients report. This is something that in clinical practice we tend to push to one side. We have some medications for pain management that we sometimes use for sleep, but cannabis use at nighttime seems to be a very powerful agent to improve sleep quality," observed Dr. Mark F. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit of McGill University in Montreal.

Dr. Bowling estimated that roughly 80% of his MS patients have little or no interest in medical marijuana. Those who are using it span a spectrum ranging from patients who were recreational users of pot before their MS diagnosis and who now seek beneficial MS effects or simply a license to use it recreationally, to elderly individuals with no history of marijuana use who have found cannabis is the only thing that effectively relieves some of their symptoms.

The neurologist noted two glaring paradoxes that emerged from his review of the clinical trials literature on medical marijuana for MS. One is that only 2 of the 19 studies utilized smoked marijuana, even though it’s far and away the most readily available form of the agent for U.S. patients. The most widely studied agent nabiximols (Sativex), an extract formulated as an oral spray – is approved as a prescription drug in Canada, the United Kingdom, and other countries, but not in the United States. And while Marinol and oral nabilone (Cesamet) are approved by the Food and Drug Administration, they’re not widely prescribed.

"I find it particularly challenging to apply the medical literature in this area to clinical situations. In our clinical practice, the way it seems to work out best is for patients to experiment on their own with marijuana as a prn add-on to their spasticity and/or pain medications, especially at bedtime or, if symptoms are worse, in the afternoon. But the dose, frequency, formulation, quality control ... it’s a real challenge. It’s like there are parallel universes of care, where we’re prescribing the conventional medications, and then we find out that the patients are also using marijuana," Dr. Bowling said.

The other paradox is the huge disconnect between the generally quite favorable subjective patient self-reports of improvement in spasticity and the largely negative objective results. The explanation may lie in part in the inadequacy of the Ashworth score as an outcome measure. It has come under frequent criticism, since some approved antispasticity medications have shown only modest or no improvement in Ashworth scores. But the limitations of the Ashworth score are probably only part of the story, in Dr. Bowling’s view.

"Patients’ assessments are 24/7; ours is a brief clinical visit at a prespecified time. Also, there is a pain component to spasticity, so for some patients who feel their spasticity is improving with the use of marijuana it may just be the pain aspect of the spasticity, or a euphoric view of the world that’s changing their perception of how severe the spasticity is. But for some patients, maybe it doesn’t matter whether it’s a subjective or objective assessment that’s improving, especially for those who don’t have high physical or cognitive demands during the day," he said.

Dr. Bowling reported having no conflicts of interest. Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.

bjancin@frontlinemedcom.com

ORLANDO – The randomized trials evidence supporting a positive clinical effect for medical marijuana in relieving symptoms of multiple sclerosis is strongest for improvement of pain, patient-reported spasticity, and sleep disturbances.

That’s the clear message from an analysis of the 19 published, reasonable-quality randomized trials of cannabis use in patients with MS, Dr. Allen C. Bowling reported at the fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

"That’s consistent with my personal observation in a state where we’ve had medical marijuana for 12 years and where recreational marijuana was approved in last November’s election. The most consistent effect my patients report is on nocturnal pain and/or spasticity, which is consistent with the results of the clinical trials. The patients typically use a little bit at bedtime," according to Dr. Bowling, medical director of the MS service and director of the complementary and alternative medicine service at the Colorado Neurological Institute, Englewood.

The evidence that medical marijuana is of benefit for the bladder dysfunction associated with MS is weaker: Of 9 clinical trials that included bladder dysfunction as an endpoint, 4 were positive, 5 negative.

Occupying the bottom tier in terms of evidence-based therapy are objectively measured spasticity and tremor. Of 13 clinical trials that incorporated objective, clinician-assessed spasticity as an endpoint, only 2 were positive, with 11 negative. And none of the 5 decent-quality randomized trials that examined medical marijuana for relief of tremor in MS patients was positive.

In contrast, 9 of 11 studies that looked at pain as an endpoint reported a positive effect. Of 13 studies with patient-reported spasticity as an endpoint, 9 were positive, 4 negative. And of 6 randomized trials with sleep quality as an endpoint, 5 were positive, 1 negative, noted Dr. Bowling, who is clinical professor of neurology at the University of Colorado, Denver.

Medical marijuana is now legal in 18 states and the District of Columbia.

The largest and in Dr. Bowling’s view one of the best-conducted randomized trials in the field was the multicenter U.K. CAMS trial. The 15-week study included 630 MS patients who were randomized to oral tetrahydrocannabinol (Marinol); Cannador, an oral capsule containing a standardized amount of whole-plant extract; or placebo. The investigators found no significant difference between the cannabis-based therapies and placebo in improving spasticity as objectively measured using the Ashworth score, which was the primary study endpoint. However, the two active treatment arms did show significant benefit in terms of the secondary endpoints of improvement in pain, self-reported spasticity, and sleep (Lancet 2003;362:1517-26).

Another speaker at the session on prescribing medical marijuana underscored the beneficial effect on sleep disruption.

"In every single population – whether it’s Crohn’s disease, epilepsy, HIV, noncancer pain, cancer pain – improved sleep is always one of the most robust outcomes patients report. This is something that in clinical practice we tend to push to one side. We have some medications for pain management that we sometimes use for sleep, but cannabis use at nighttime seems to be a very powerful agent to improve sleep quality," observed Dr. Mark F. Ware, a family physician and anesthesiologist who is director of clinical research at the Alan Edwards Pain Management Unit of McGill University in Montreal.

Dr. Bowling estimated that roughly 80% of his MS patients have little or no interest in medical marijuana. Those who are using it span a spectrum ranging from patients who were recreational users of pot before their MS diagnosis and who now seek beneficial MS effects or simply a license to use it recreationally, to elderly individuals with no history of marijuana use who have found cannabis is the only thing that effectively relieves some of their symptoms.

The neurologist noted two glaring paradoxes that emerged from his review of the clinical trials literature on medical marijuana for MS. One is that only 2 of the 19 studies utilized smoked marijuana, even though it’s far and away the most readily available form of the agent for U.S. patients. The most widely studied agent nabiximols (Sativex), an extract formulated as an oral spray – is approved as a prescription drug in Canada, the United Kingdom, and other countries, but not in the United States. And while Marinol and oral nabilone (Cesamet) are approved by the Food and Drug Administration, they’re not widely prescribed.

"I find it particularly challenging to apply the medical literature in this area to clinical situations. In our clinical practice, the way it seems to work out best is for patients to experiment on their own with marijuana as a prn add-on to their spasticity and/or pain medications, especially at bedtime or, if symptoms are worse, in the afternoon. But the dose, frequency, formulation, quality control ... it’s a real challenge. It’s like there are parallel universes of care, where we’re prescribing the conventional medications, and then we find out that the patients are also using marijuana," Dr. Bowling said.

The other paradox is the huge disconnect between the generally quite favorable subjective patient self-reports of improvement in spasticity and the largely negative objective results. The explanation may lie in part in the inadequacy of the Ashworth score as an outcome measure. It has come under frequent criticism, since some approved antispasticity medications have shown only modest or no improvement in Ashworth scores. But the limitations of the Ashworth score are probably only part of the story, in Dr. Bowling’s view.

"Patients’ assessments are 24/7; ours is a brief clinical visit at a prespecified time. Also, there is a pain component to spasticity, so for some patients who feel their spasticity is improving with the use of marijuana it may just be the pain aspect of the spasticity, or a euphoric view of the world that’s changing their perception of how severe the spasticity is. But for some patients, maybe it doesn’t matter whether it’s a subjective or objective assessment that’s improving, especially for those who don’t have high physical or cognitive demands during the day," he said.

Dr. Bowling reported having no conflicts of interest. Dr. Ware has received lecture fees from the Canadian Consortium for the Investigation of the Cannabinoids and a research grant and honoraria from Valeant for conducting a randomized trial of nabilone in fibromyalgia patients.

bjancin@frontlinemedcom.com