Kerri Wachter

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

NATIONAL HARBOR, MD. – Pharmaceutical companies are stepping up to address increasing opioid abuse and misuse by developing innovative abuse-deterrent formulations and drug delivery systems, Dr. Lynn R. Webster said at the annual meeting of the American Academy of Pain Medicine.

Dr. Webster discussed several new opioid formulations that are currently available and some promising technologies in the pipeline. Dr. Webster is board certified in anesthesiology and pain medicine and is certified in addiction medicine. He is also the medical director and founder of the Lifetree Clinical Research and Pain Clinic in Salt Lake City.

New Opioids. In January 2011, the Food and Drug Administration approved Abstral (Prostrakan), a fentanyl transmucosal tablet indicated for the management of breakthrough cancer pain in adults. As an alternative to oral tablets or injections of fentanyl pain medications, the quick-dissolving tablet is placed under the tongue, providing very fast relief for cancer-related pain in patients already receiving opioids for pain treatment.

Approved in 2010, Exalgo is an extended-release formulation of hydromorphone indicated for once-daily administration for the management of moderate to severe pain in opioid-tolerant patients who require continuous, around-the-clock opioid analgesia for an extended period. Exalgo (Mallinckrodt) is not intended for use as an as-needed analgesic. The formulation utilizes a new osmotic, controlled-release oral delivery system in which osmosis attracts water in the body to the inside of the capsule to trigger release of hydromorphone. It takes about 6 hours for effective levels of hydromorphone to be released and 4-5 days for drug levels to reach a steady state in the body, Dr. Webster said.

There has been a resurgence of interest in buprenorphine. This drug has been around for several decades, but is now being used to treat chronic pain. Buprenorphine is a partial mu-opioid agonist, an antagonist at the kappa-opioid receptor, and a partial agonist at the ORL1/nociceptin and delta-opioid receptors. "There is a little bit of complexity with how the pharmacology of this drug works. We probably don’t understand clinically what all of that means yet," Dr. Webster said. Buprenorphine is the only opioid classified as a schedule III drug, making it an attractive choice for pain management. Buprenorphine also is associated with fewer of the side effects typical of opioids, such as respiratory depression.

In 2010, the FDA approved Butrans, an extended-release buprenorphine patch (Purdue Pharma), in 5-, 10- and 20-mcg/hour doses. The drug is indicated for the management of moderate to severe chronic pain in patients requiring continuous, around-the-clock opioid treatment for an extended period.

Notably, Subutex (buprenorphine monotherapy) and Suboxone (a buprenorphine/naloxone combination product) are approved for use in opioid addiction treatment, though other forms of the drug are not. However, other forms of buprenorphine are commonly used off-label for the management of addiction disorders, Dr. Webster said. Because buprenorphine is an opioid partial agonist, its maximal effects are less than those of full agonists (like heroin and methadone). At low doses, buprenorphine is thought to produce enough of an agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine has poor oral bioavailability and only moderate sublingual bioavailability.

In the Pipeline. Acurox (Acura Pharmaceuticals and King Pharmaceuticals [now part of Pfizer]) is an oral immediate-release oxycodone tablet with a proposed indication for the relief of moderate to severe pain. Acurox is formulated so that if the tablets are dissolved in an attempt to extract the opioid for intravenous injection, the tablets turn into a viscous gel mixture with the active drug trapped in the gel. The Aversion technology used also causes burning and irritation of the nasal passages if the drug is crushed and snorted.

Last year, the FDA rejected an application for a version of the drug containing niacin, which was formulated so that the uncomfortable "niacin flush" would deter overuse of the drug. In February 2011, the FDA accepted a new drug application for Acurox (oxycodone) tablets without niacin.

MoxDuo (QRxPharma) is an immediate-release dual opioid intended for the acute management of moderate to severe pain. The drug is a combination of morphine and oxycodone that has been clinically shown to have a synergistic effect on pain with a significant reduction of total opioid dose and side effects.

"This formulation is built upon that thought that there are different receptor selectivities to an opioid," Dr. Webster said. Because opioid receptors differ, "you can get enhanced analgesia with using overall less morphine equivalents, or you could get fewer side effects with the same level of analgesia, when you combine two different opioids."

Collegium Pharmaceuticals is developing an abuse-deterrent, sustained-release oral oxycodone formulation (COL-003). The DETERx delivery technology consists of a multiparticulate matrix formulation in a capsule that is designed to be less susceptible to common methods of tampering, such as crushing or chewing prior to ingestion. Company studies showed that the plasma profile for the new-formulation pill was bioequivalent whether it was chewed or taken whole as intended. "It’s an abuse-resistant formulation in that they can’t extract more than is intended for its delivery," Dr. Webster said.

Remoxy (Pain Therapeutics and King Pharmaceuticals) is a long-acting oral oxycodone for the treatment of moderate to severe chronic pain. "This is what I consider an opioid-resistant formulation, meaning it’s got a barrier that is hard to crush, hard to manipulate; and it’s hard to extract" the oxycodone, Dr. Webster said. "It can’t be chewed, snorted, or injected very easily."

A new transmucosal buprenorphine patch is also in the trial phase. According to PharmacoFore, the delivery system’s developer, the novel Bio-Activated Molecular Delivery (Bio-MD) technology deters prescription drug abuse at a molecular level.

"This technology does not involve the reformulation of existing opioid drugs in physical matrices that are easily circumvented by simple extraction methods. Our opioid Bio-MD systems are ‘activated’ to release clinically effective opioid drugs only when exposed to the correct physiologic conditions (i.e., ingested)," the company noted on its Web site.

Essentially, an opioid molecule – any opioid – is attached to the delivery compound. "It’s kind of like a clock. The intrinsic trypsin in our GI tract will activate that clock, which will ... allow that drug to be released," Dr. Webster said. The clock determines how much time it will take for the active compound to be released.

"It’s very early on," he cautioned. The delivery system is in phase I trials. Still, "it looks very interesting that they have the technology now to address multipill abuse. There are ways to design the same technologies so that the triggering system will only allow a certain number of pills or milligrams of medication to be absorbed." Thus, regardless of how many pills an individual takes, no more than the prescribed dose is bioavailable.

Dr. Webster reported that he has significant financial relationships with a number of pharmaceutical companies, including King Pharmaceuticals and Collegium Pharmaceutical.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We're in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization's new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It's estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year's World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes's concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we're facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x '20 initiative).

• Recalibrating and better communicating the FDA's requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services' Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies' efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We're in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization's new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It's estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year's World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes's concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we're facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x '20 initiative).

• Recalibrating and better communicating the FDA's requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services' Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies' efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We're in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization's new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It's estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year's World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes's concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we're facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x '20 initiative).

• Recalibrating and better communicating the FDA's requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services' Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies' efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

Growing antimicrobial resistance from indiscriminate use of existing antibiotics and a lack of new ones in development could mean a return to the preantibiotic era of medicine with disastrous consequences.

"We’re in a time of increasing antibiotic resistance and decreasing introduction of new antibiotic drugs ... [this] sets us up for the possibility of returning to the preantibiotic era ... you know historically the devastating consequences that people faced at that time," Dr. James Hughes, president of the Infectious Diseases Society of America, said during a press conference on April 7.

The press conference, sponsored by IDSA, was held to announce the release of the organization’s new policy paper, "Combating Antimicrobial Resistance: Policy Recommendations to Save Lives." The paper is also published in the journal Clinical Infectious Diseases (Clin. Infect. Dis. 2011;52[suppl 5] [doi:10.1093/cid/cir154]).

The incidence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Klebsiella, and others has soared in the past 2 decades. It’s estimated that each year, these infections kill nearly 100,000 U.S. hospital patients. At the same time, while 16 new antibiotics were approved between 1983 and 1987, only 2 have been approved since 2008.

One-third of Acinetobacter and 7% of Klebsiella infections reported to the National Healthcare Safety Network between 2006 and 2008 were resistant to all commonly used antibiotics.

The crisis is so alarming that the World Health Organization has made antibiotic resistance the central focus of this year’s World Health Day, the goal of which is to highlight a global public health issue of critical concern.

FDA Commissioner Margaret Hamburg echoed Dr. Hughes’s concern about the alarming situation posed by antimicrobial resistance. "The problem of antimicrobial resistance is one in which we all have a stake. ... We worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs available for clinical use," she said. "It is more than just hypothetical when people like Dr. Hughes talk about a return to the pre-antibiotic era, in which we no longer have effective tools to treat serious infectious disease."

In particular, the IDSA stresses the need for better stewardship of existing antibiotic drugs and to increase incentives for research and development of new antibiotic drugs by drug companies. "We must take action now ... the sad irony is that we’re facing a situation in which tried-and-true drugs are losing their value at the same time that the pipeline of new drugs to treat these diseases is distressingly devoid of innovative drugs," said Dr. Hamburg.

At the national level, two bills already have been introduced to address both of these problems—the Strategies to Address Antimicrobial Resistance (STAAR) Act and the Generating Antibiotic Incentives Now (GAIN) Act.

In the new policy paper, the IDSA also recommends:

• Creating incentives – and removing economic and regulatory disincentives – to encourage drug companies to develop new antibiotics (IDSA has proposed a goal of developing 10 new systemic antibiotics by 2020 – the 10 x ’20 initiative).

• Recalibrating and better communicating the FDA’s requirements for new antibiotic approvals.

• Funding antibiotic research and development efforts under the Department of Health and Human Services’ Biomedical Advanced Research and Development Authority and proposed independent strategic investment firm.

• Supporting research and development for rapid diagnostic tests for use at the point of care to identify the cause of infections more quickly, in order to better use existing antibiotics.

• Designating a leader within HHS to facilitate coordination of federal agencies’ efforts and better utilize outside experts.

• Promoting the judicious use of available antibiotics in all settings – both in humans and in food animals – through better stewardship programs and infection control practices.

• Creating an antimicrobial innovation and conservation fee – charged against the wholesale purchase of antibiotics used in humans, animals, plants, and aquaculture – to help pay for drug development and stewardship.

• Strengthening public health measures – such as surveillance, data collection, and immunization – and research that leads to new interventions to limit the spread of resistant organisms.

• Establishing nonprofit public-private partnerships to invest in bringing new antibiotics to market even though the market may be a small one.

For more information, visit IDSA.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.

An international panel has revised the McDonald criteria for the diagnosis of multiple sclerosis to simplify the use of imaging in determining the dissemination of central nervous system lesions both in space and time, while preserving sensitivity and specificity.

The new revisions also address the applicability of the criteria in non-Western Caucasian populations – specifically Asian and Latin American populations – and children and adolescents.

The changes update the 2005 version of the criteria based on new evidence and consensus, which "pointed to the need for their simplification to improve their comprehension and utility and for evaluating their appropriateness in populations that differ from the largely Western Caucasian adult population from which the criteria were derived," wrote lead author Dr. Chris H. Polman and his coauthors (Ann. Neurol. 2011;69:292-302).

In an accompanying editorial, Dr. Richard A. Rudick agreed (Ann. Neurol. 2011;69:234-6). "The McDonald criteria were not just for clinical trials, but for neurologists in practice. However, some neurologists found the McDonald criteria complex and difficult to use in the clinic, and even experienced MS specialists were uncertain about some aspects of the criteria." Dr. Rudick is the director of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic.

The 2010 revisions to the McDonald criteria are intended to allow a more rapid diagnosis of MS in some instances, with equivalent or improved specificity or sensitivity, and will clarify and simplify the diagnostic process with fewer required MRI examinations, according to Dr. Polman of the neurology department at the Free University in Amsterdam, and his coauthors.

The International Panel on Diagnosis of MS reviewed published research related to the diagnosis of MS and to the original and revised McDonald criteria, gathered from literature searches of English-language publications.

The panel stressed that the updated criteria should only be applied to patients who present with a typical clinically isolated syndrome (CIS) suggestive of MS or symptoms consistent with a central nervous system (CNS) inflammatory demyelinating disease, because the development and validation of the criteria have been limited to patients with such presentations. It also remains imperative that alternative diagnoses be considered and excluded.

Neuromyelitis Optica and Spectrum Disorders. The panel focused on the differential diagnosis for MS of neuromyelitis optica (NMO) and NMO spectrum disorders, because "there is increasing evidence of relapsing CNS demyelinating disease characterized by involvement of optic nerves (unilateral or bilateral optic neuritis), often severe myelopathy with MRI evidence of longitudinally extensive spinal cord lesions, often normal brain MRI (or with abnormalities atypical for MS), and serum aquaporin-4 (AQP4) autoantibodies."

The panel agreed that this phenotype should be separated out because the clinical course, prognosis, and underlying pathophysiology are different from those of typical MS. The response of patients with NMO and its spectrum disorders to some available MS disease-modifying therapies is often poor.

The panel recommended that this disorder should be carefully considered in the differential diagnosis of all patients presenting with clinical and MRI features that are strongly suggestive of NMO or NMO spectrum disorder, especially if:

• myelopathy is associated with MRI-detected spinal cord lesions longer than three spinal segments and primarily involving the central part of the spinal cord on axial sections;

• optic neuritis is bilateral and severe or associated with a swollen optic nerve or chiasm lesion or an altitudinal scotoma; and

• intractable hiccough, nausea, or vomiting is present for more than 2 days with evidence of a periaqueductal medullary lesion on MRI.

AQP4 serum testing should be used to help make a differential diagnosis between NMO and MS.

Dissemination in Space and Time. While the panel agreed that the underlying concepts of the original (2001) and revised (2005) criteria are still valid, they recommended key changes related to the use and interpretation of imaging criteria for dissemination in space (DIS) and dissemination in time (DIT) as articulated by the recently published work from the Magnetic Imaging in MS (MAGNIMS) research group.

The European MAGNIMS multicenter collaborative research network compared the Barkhof/Tintoré criteria for DIS (Brain 1997;120:2059-69; Am. J. Neuroradiol. 2000;21:702-6) – used in previous McDonald criteria – with simplified criteria developed by Swanton and colleagues (Lancet Neurol. 2007;6:677-86; J. Neurol. Neurosurg. Psychiatry 2006;77:830-3).

Based on the MAGNIMS analysis, the panel said that DIS can be demonstrated with at least one T2 lesion in at least two of four locations considered characteristic for MS (juxtacortical, periventricular, infratentorial, and spinal cord), excluding lesions within the symptomatic region in patients with brainstem or spinal cord syndromes.

These new criteria for DIS can simplify the diagnostic process for MS, while preserving specificity and improving sensitivity.

The presence of both gadolinium-enhancing and nonenhancing lesions on the baseline MRI can substitute for a follow-up scan to confirm DIT, as long as it can be reliably determined that the gadolinium-enhancing lesion is not due to non-MS pathology.

Based on these changes, a diagnosis of MS can be made in some CIS patients on the basis of a single MRI. The panel stated that this change simplifies the diagnostic process without reducing accuracy.

Cerebrospinal Fluid. The panel still agreed that positive cerebrospinal fluid (CSF) findings – elevated immunoglobulin G (IgG) index or two or more oligoclonal bands – can be important to support the inflammatory demyelinating nature of the underlying condition, to evaluate alternative diagnoses, and to predict clinically definite MS. However, when applying the simplified MAGNIMS imaging criteria for DIS and DIT, the panel believes that changing the MRI requirements in CSF-positive patients is not appropriate.

Primary Progressive MS. The panel recommended replacing previous brain imaging criteria for primary progressive MS (PPMS) with the new MAGNIMS criteria for DIS. In addition to 1 year of disease progression, the new criteria for PPMS require two of the following: at least one T2 lesion in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial); at least two T2 lesions in the cord; or positive CSF (isoelectric focusing evidence of oligoclonal bands with or without an elevated IgG index).

Pediatric Patients. The panel agreed that the proposed MAGNIMS-based MRI revisions for DIS will also work well for most pediatric MS patients – especially those with acute demyelination, presenting as CIS – because most pediatric patients will have more than two lesions and are very likely to have lesions in two of the four specified CNS locations.

However, an estimated 15%-20% of pediatric MS patients (most younger than 11 years) present with encephalopathy and multifocal neurological deficits, which are difficult to distinguish from acute disseminated encephalomyelitis.

For these patients, the panel concluded that application of the revised MAGNIMS-based criteria for DIS and DIT on initial MRI would be inappropriate. Instead, serial clinical and MRI observations are required to confirm a diagnosis of MS. In this young age group, there can be marked lesion resolution following an initial attack prior to emergence over time of new lesions and attacks leading to a diagnosis of MS, the panel noted.

Other Populations. A phenotype characterized by NMO, longitudinally extensive spinal cord lesions, and AQP4 autoantibody seropositivity has been relatively more common among Asian patients with CNS inflammatory demyelinating disease than in Western populations. However, there is some uncertainty – especially in Asia – about whether MS and NMO are distinct. If so, it is unclear how these patients should be distinguished. "Failure to make the correct diagnosis in patients with NMO may impact treatment," the panel noted.

The panel recommended testing for AQP4 autoantibodies with validated assays in patients who are suspected of having NMO or NMO spectrum disorders, especially in patients with an Asian or Latin American genetic background because of the higher prevalence of the disease in these populations.

However, the current evidence suggests that once NMO and NMO spectrum disorders have been excluded, Western-type MS in Asia or Latin America is not fundamentally different from typical MS in the Caucasian population, the panel concluded. The MAGNIMS MRI criteria would apply to such patients, although confirmatory studies should be done.

Dr. Polman, Dr. Rudick, and several other panelists reported significant financial relationships with several pharmaceutical companies.