Sharon Worcester

DESTIN, FLA. – Opioid rotation is a common and potentially beneficial practice for helping to relieve chronic pain in patients who require ongoing opioid therapy, but there is very little data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, Dr. Perry Fine said at the Congress of Clinical Rheumatology.

Clinicians should consider opioid rotation when patients on chronic opioid therapy experience intolerable adverse effects, or when benefits are inadequate despite dose increases, according to recently published clinical guidelines (J. Pain 2009;10:113-30).

However, it is important to consider a number of factors before making changes in treatment, including demographic, disease-related, and treatment-related factors, as well as comorbidities, concomitant pharmacotherapy, drug sensitivities, and social situation, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

If a decision is made to convert a patient’s treatment, a two-step, safety-focused approach is needed, he said.

Step 1 involves an "automatic safety factor" calculation. That is, the equianalgesic dose of the new opioid should be calculated via an equianalgesic table such as a mu-agonist dose chart, and, with a few exceptions, an automatic dose reduction of 25%-50% should be made, except if the new drug is methadone or transdermal fentanyl.

A 25% reduction for opioids (other than methadone or fentanyl) is adequate in patients with no risk factors and/or if the switch is to a different route of administration of the same drug. A 50% reduction is needed in those receiving a relatively high dose of the current opioid, those who are elderly or frail, and those of Chinese lineage, as the Chinese population has been shown to be at increased risk of poor metabolism of opioid drugs, Dr. Fine said.

If the switch is to methadone, a 75%-90% dose reduction is needed, and if the switch is to transdermal fentanyl, use the reduction that is built into the conversion charts provided in the prescribing information, he advised.

If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he added.

The second safety-focused conversion step involves patient-specific adjustments. The patient should be assessed for pain severity and other medical or psychosocial characteristics, and appropriate additional adjustments should be made to the initial dose of the new opioid. For severe pain, consider a dose increase. If pain is under control, but the patient is experiencing adverse effects, any adjustments to the dose should be minimal.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, an additional 10%-30% dose reduction should be considered, Dr. Fine said.

He used as an example a case involving a patient with mild renal insufficiency who was undergoing a switch from morphine to hydromorphone. The patient had moderate pain, mild confusion, and was on multiple other medications. According to step 1, an automatic 25% reduction in the equianalgesic hydromorphone dose would be calculated. According to step 2, an additional 25% reduction would be taken because of the patient’s decreased renal clearance, cognitive problems, and potential drug-drug interactions. Dosage would then be titrated based on the patient’s response.

It is important that a strategy for frequent assessment of initial response be in place, Dr. Fine said, noting that this may involve regular phone calls to the patient or scheduled office visits. This will allow for improved safety and appropriate titration, he said.

Dr. Fine offered the following examples of initial dose calculation in three common analgesic conversions:

• To convert controlled-release oxycodone (60 mg oral dose twice daily) to controlled-release morphine:

1. Calculate the total oxycodone 24-hour dose (120 mg).

2. Determine the morphine dose equivalency (20 mg oxycodone = 30 mg morphine).

3. Convert the 24-hour oxycodone dose to the morphine dose (120 mg oxycodone = 180 mg morphine).

4. Reduce the morphine dose by 25% (135 mg morphine).

5. Split the total morphine dose to the twice-daily dose (67.5 mg). Because the controlled-release (extended-release) morphine is not provided in this exact dose, give the closest available dose (60 mg, twice daily).

• To convert controlled-release morphine (30 mg oral dose twice daily) to transdermal fentanyl:

1. Calculate the total morphine 24-hour dose (60 mg).

2. Use the prescribing information to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr transdermal fentanyl patch).

3. Prescribe 25 mcg/hr transdermal fentanyl patch to be changed every 3 days. Supply patient with five patches (a 15-day supply); instruct patient on application, and follow-up by phone or in office within 2-3 days.

• To convert methadone (20 mg oral dose three times daily) to extended-release oxymorphone:

1. Calculate the total methadone 24-hour dose (60 mg daily).

2. Use mu-agonist dose chart to calculate oxymorphone dose equivalency to methadone (5 mg methadone = 10 mg oxymorphone).

3. Convert the 24-hour methadone dose to oxymorphone dose (60 mg methadone = 120 mg oxymorphone).

4. Reduce the dose by 50% and split the 50% total calculated oxymorphone dosage to a twice-daily dose. Prescribe oxymorphone ER (30 mg oral dose every 12 hours).

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King (now Pfizer), Meda, and Purdue-Pharma. He also is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Opioid rotation is a common and potentially beneficial practice for helping to relieve chronic pain in patients who require ongoing opioid therapy, but there is very little data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, Dr. Perry Fine said at the Congress of Clinical Rheumatology.

Clinicians should consider opioid rotation when patients on chronic opioid therapy experience intolerable adverse effects, or when benefits are inadequate despite dose increases, according to recently published clinical guidelines (J. Pain 2009;10:113-30).

However, it is important to consider a number of factors before making changes in treatment, including demographic, disease-related, and treatment-related factors, as well as comorbidities, concomitant pharmacotherapy, drug sensitivities, and social situation, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

If a decision is made to convert a patient’s treatment, a two-step, safety-focused approach is needed, he said.

Step 1 involves an "automatic safety factor" calculation. That is, the equianalgesic dose of the new opioid should be calculated via an equianalgesic table such as a mu-agonist dose chart, and, with a few exceptions, an automatic dose reduction of 25%-50% should be made, except if the new drug is methadone or transdermal fentanyl.

A 25% reduction for opioids (other than methadone or fentanyl) is adequate in patients with no risk factors and/or if the switch is to a different route of administration of the same drug. A 50% reduction is needed in those receiving a relatively high dose of the current opioid, those who are elderly or frail, and those of Chinese lineage, as the Chinese population has been shown to be at increased risk of poor metabolism of opioid drugs, Dr. Fine said.

If the switch is to methadone, a 75%-90% dose reduction is needed, and if the switch is to transdermal fentanyl, use the reduction that is built into the conversion charts provided in the prescribing information, he advised.

If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he added.

The second safety-focused conversion step involves patient-specific adjustments. The patient should be assessed for pain severity and other medical or psychosocial characteristics, and appropriate additional adjustments should be made to the initial dose of the new opioid. For severe pain, consider a dose increase. If pain is under control, but the patient is experiencing adverse effects, any adjustments to the dose should be minimal.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, an additional 10%-30% dose reduction should be considered, Dr. Fine said.

He used as an example a case involving a patient with mild renal insufficiency who was undergoing a switch from morphine to hydromorphone. The patient had moderate pain, mild confusion, and was on multiple other medications. According to step 1, an automatic 25% reduction in the equianalgesic hydromorphone dose would be calculated. According to step 2, an additional 25% reduction would be taken because of the patient’s decreased renal clearance, cognitive problems, and potential drug-drug interactions. Dosage would then be titrated based on the patient’s response.

It is important that a strategy for frequent assessment of initial response be in place, Dr. Fine said, noting that this may involve regular phone calls to the patient or scheduled office visits. This will allow for improved safety and appropriate titration, he said.

Dr. Fine offered the following examples of initial dose calculation in three common analgesic conversions:

• To convert controlled-release oxycodone (60 mg oral dose twice daily) to controlled-release morphine:

1. Calculate the total oxycodone 24-hour dose (120 mg).

2. Determine the morphine dose equivalency (20 mg oxycodone = 30 mg morphine).

3. Convert the 24-hour oxycodone dose to the morphine dose (120 mg oxycodone = 180 mg morphine).

4. Reduce the morphine dose by 25% (135 mg morphine).

5. Split the total morphine dose to the twice-daily dose (67.5 mg). Because the controlled-release (extended-release) morphine is not provided in this exact dose, give the closest available dose (60 mg, twice daily).

• To convert controlled-release morphine (30 mg oral dose twice daily) to transdermal fentanyl:

1. Calculate the total morphine 24-hour dose (60 mg).

2. Use the prescribing information to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr transdermal fentanyl patch).

3. Prescribe 25 mcg/hr transdermal fentanyl patch to be changed every 3 days. Supply patient with five patches (a 15-day supply); instruct patient on application, and follow-up by phone or in office within 2-3 days.

• To convert methadone (20 mg oral dose three times daily) to extended-release oxymorphone:

1. Calculate the total methadone 24-hour dose (60 mg daily).

2. Use mu-agonist dose chart to calculate oxymorphone dose equivalency to methadone (5 mg methadone = 10 mg oxymorphone).

3. Convert the 24-hour methadone dose to oxymorphone dose (60 mg methadone = 120 mg oxymorphone).

4. Reduce the dose by 50% and split the 50% total calculated oxymorphone dosage to a twice-daily dose. Prescribe oxymorphone ER (30 mg oral dose every 12 hours).

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King (now Pfizer), Meda, and Purdue-Pharma. He also is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Opioid rotation is a common and potentially beneficial practice for helping to relieve chronic pain in patients who require ongoing opioid therapy, but there is very little data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, Dr. Perry Fine said at the Congress of Clinical Rheumatology.

Clinicians should consider opioid rotation when patients on chronic opioid therapy experience intolerable adverse effects, or when benefits are inadequate despite dose increases, according to recently published clinical guidelines (J. Pain 2009;10:113-30).

However, it is important to consider a number of factors before making changes in treatment, including demographic, disease-related, and treatment-related factors, as well as comorbidities, concomitant pharmacotherapy, drug sensitivities, and social situation, said Dr. Fine, professor of anesthesiology at the University of Utah, Salt Lake City.

If a decision is made to convert a patient’s treatment, a two-step, safety-focused approach is needed, he said.

Step 1 involves an "automatic safety factor" calculation. That is, the equianalgesic dose of the new opioid should be calculated via an equianalgesic table such as a mu-agonist dose chart, and, with a few exceptions, an automatic dose reduction of 25%-50% should be made, except if the new drug is methadone or transdermal fentanyl.

A 25% reduction for opioids (other than methadone or fentanyl) is adequate in patients with no risk factors and/or if the switch is to a different route of administration of the same drug. A 50% reduction is needed in those receiving a relatively high dose of the current opioid, those who are elderly or frail, and those of Chinese lineage, as the Chinese population has been shown to be at increased risk of poor metabolism of opioid drugs, Dr. Fine said.

If the switch is to methadone, a 75%-90% dose reduction is needed, and if the switch is to transdermal fentanyl, use the reduction that is built into the conversion charts provided in the prescribing information, he advised.

If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he added.

The second safety-focused conversion step involves patient-specific adjustments. The patient should be assessed for pain severity and other medical or psychosocial characteristics, and appropriate additional adjustments should be made to the initial dose of the new opioid. For severe pain, consider a dose increase. If pain is under control, but the patient is experiencing adverse effects, any adjustments to the dose should be minimal.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, an additional 10%-30% dose reduction should be considered, Dr. Fine said.

He used as an example a case involving a patient with mild renal insufficiency who was undergoing a switch from morphine to hydromorphone. The patient had moderate pain, mild confusion, and was on multiple other medications. According to step 1, an automatic 25% reduction in the equianalgesic hydromorphone dose would be calculated. According to step 2, an additional 25% reduction would be taken because of the patient’s decreased renal clearance, cognitive problems, and potential drug-drug interactions. Dosage would then be titrated based on the patient’s response.

It is important that a strategy for frequent assessment of initial response be in place, Dr. Fine said, noting that this may involve regular phone calls to the patient or scheduled office visits. This will allow for improved safety and appropriate titration, he said.

Dr. Fine offered the following examples of initial dose calculation in three common analgesic conversions:

• To convert controlled-release oxycodone (60 mg oral dose twice daily) to controlled-release morphine:

1. Calculate the total oxycodone 24-hour dose (120 mg).

2. Determine the morphine dose equivalency (20 mg oxycodone = 30 mg morphine).

3. Convert the 24-hour oxycodone dose to the morphine dose (120 mg oxycodone = 180 mg morphine).

4. Reduce the morphine dose by 25% (135 mg morphine).

5. Split the total morphine dose to the twice-daily dose (67.5 mg). Because the controlled-release (extended-release) morphine is not provided in this exact dose, give the closest available dose (60 mg, twice daily).

• To convert controlled-release morphine (30 mg oral dose twice daily) to transdermal fentanyl:

1. Calculate the total morphine 24-hour dose (60 mg).

2. Use the prescribing information to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr transdermal fentanyl patch).

3. Prescribe 25 mcg/hr transdermal fentanyl patch to be changed every 3 days. Supply patient with five patches (a 15-day supply); instruct patient on application, and follow-up by phone or in office within 2-3 days.

• To convert methadone (20 mg oral dose three times daily) to extended-release oxymorphone:

1. Calculate the total methadone 24-hour dose (60 mg daily).

2. Use mu-agonist dose chart to calculate oxymorphone dose equivalency to methadone (5 mg methadone = 10 mg oxymorphone).

3. Convert the 24-hour methadone dose to oxymorphone dose (60 mg methadone = 120 mg oxymorphone).

4. Reduce the dose by 50% and split the 50% total calculated oxymorphone dosage to a twice-daily dose. Prescribe oxymorphone ER (30 mg oral dose every 12 hours).

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King (now Pfizer), Meda, and Purdue-Pharma. He also is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – Methadone can be an effective treatment for chronic pain, but there are a number of concerns that must be considered when prescribing this opioid, Dr. Perry G. Fine said at the Congress of Clinical Rheumatology.

Among the benefits of the effective mu-opioid analgesic with N-methyl-d-aspartate receptor antagonist properties are its low cost, dosing formulation versatility, long duration of action, and favorable metabolic profile. However, it also has highly variable pharmacokinetics, a very long half-life compared with its analgesic duration of action, and nonlinear dose conversion.

While prescribing has increased dramatically over the last several years, especially compared with other opioids, so has the number of methadone-related deaths relative to deaths associated with other opioids, according to a 2007 report from the National Drug Intelligence Center.

Prescribing this drug requires methadone-specific knowledge and vigilance on the part of the prescriber, as well as a highly responsible patient and/or caregiver who will monitor use and side effects, particularly during titration, according to Dr. Fine, professor of anesthesiology at the Pain Research Center, University of Utah, Salt Lake City.

Potential problems with methadone include drug-drug interactions and cardiac toxicity. Sudden death, even at therapeutic levels, can occur.

Drug-drug interactions can include adverse reactions in patients on monoamine-increasing drugs. Also, serum levels are increased by CYP3A4 and CYP2B6 inhibitors (such as certain antiretrovirals, clarithromycin, itraconazole, erythromycin, fluconazole, grapefruit juice, and more), and this has been associated with multiple overdose deaths, prompting a black-box warning advisory in 2006, Dr. Fine said.

Potential cardiac toxicity is the newest concern; treatment has been shown in some patients to prolong the corrected QT (QTc) interval, and while prescribing guidelines do not yet reflect this, a baseline electrocardiogram is advisable, Dr. Fine said.

According to current guidelines from the American Pain Society–American Academy of Pain Medicine, a reasonable starting dose in most opioid-naive patients is 2.5 mg every 8 hours. Dose increases can begin after a minimum of 10 days. Older patients, or those with renal or hepatic comorbidities, require less frequent dosing, and more cautious dose titration. Methadone treatment is not advisable for breakthrough pain because of its long half-life and variable pharmacokinetics (J. Pain. 2009;10:113-20).

Titration, according to Dr. Fine, should include dose increases of 1-2.5 mg every 8 hours in frail, older patients or patients with a history of sleep apnea, and 2.5-5 mg every 8 hours in robust younger patients. Increases should be made every 5-7 days if needed.

Advise patients or caregivers that:

– Adequate pain relief from methadone may not occur for several days or weeks.

– Methadone should be taken exactly as directed.

– Short-acting rescue medications can be used until sufficient baseline analgesia is achieved.

– Any signs of increased sedations, mental clouding, snoring, or periodic apnea should be called in (supply an emergency phone number).

– No alcohol, benzodiazepines, or other CNS depressants should be used – especially at night – unless specifically prescribed or approved by the physician who prescribed the methadone.

Also, follow up every day during dose titration by a telephone call, through home nursing, or by an office visit, and perform an in-person evaluation weekly until dose stabilization and then monthly thereafter if there are no major ongoing changes in health status, Dr. Fine said.

In-person evaluations should be performed every 3 months once the patient is fully stable, he added.

Dr. Fine has served as an advisory board member for Ameritox, Covidien, King Pharmaceuticals (now Pfizer), Meda Pharmaceuticals, and Purdue Pharma. He is a consultant for Cephalon and Johnson & Johnson.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – A conservative approach is best when it comes to making a diagnosis of Behçet’s disease, Dr. Kenneth Calamia said at the Congress of Clinical Rheumatology.

Although oral and genital ulcers are common in the disease, they also are a common manifestation of many other conditions, and it is important to consider the other possible causes first.

The importance of a Behçet’s diagnosis doesn’t have anything to do with ulcers – it has to do with the risk or presence of serious manifestations, including vascular disease, central nervous system manifestations, and uveitis, said Dr. Calamia of the department of medicine at the Mayo Clinic in Jacksonville, Fla.

"You don’t want to [needlessly] give a patient the baggage of that diagnosis," he said, noting that in patients diagnosed with Behçet’s, everything will be attributed to the disease for the rest of their lives.

In the United States and Europe, true Behçet’s is quite rare (about 0.3-7.5 cases/100,000 population), compared with places like Turkey and other "Silk Road" areas, which have a very high prevalence (100-370 cases/100,000 population). In those areas, more severe forms are much more prevalent, and the benign mucocutaneous symptoms that comprise most of the cases in America are referred to as American Behçet’s disease, Dr. Calamia said.

The term "Behçet’s syndrome" also can be used to describe the types of cases typically seen in the United States, but in many cases, the diagnosis is actually "complex aphthosis," he said, adding that Behçet’s treatment principles can nonetheless be used to help patients with this condition.

Complex aphthosis is a term used by oral dermatologists to help classify types of recurrent aphthous stomatitis. As opposed to simple aphthosis, which is characterized by episodic, short-lived lesions that are few in number, recur three to six times per year, and tend to affect nonkeratinized mucosa, complex aphthosis lesions can be continuous, numerous, large, slow-healing, and debilitating.

Keep in mind that both simple and complex aphthosis can be associated with menstruation, sprue, inflammatory bowel disease, HIV, hematologic disorders (such as cyclic neutropenia, IgA deficiency, myelodysplasia/myeloproliferation), various deficiencies (B vitamins, folate, iron, and zinc), and smoking cessation, Dr. Calamia said, explaining that smoking tends to increase keratinization, which protects against ulcers, and that protection is lost when a patient quits.

In a study conducted by an oral dermatologist several years ago, only 9% of 269 patients with severe complex aphthosis – 16% of whom also had genital ulcers – had a Behçet’s diagnosis, he noted.

Some other diagnoses in the cohort included anemia in 25%, gastrointestinal disease in 16%, hematologic disorders in 5%, mucosal disease in 6%, smoking discontinuation in 4%, and drug-related ulcers in 3%.

"[Complex aphthosis] is the diagnosis I prefer in those who have mouth and genital ulcers, but nothing else to support a diagnosis of Behçet’s," he said.

Consider the other possible causes of the ulcers, and also consider the differential diagnoses for recurrent aphthous stomatitis, which include recurrent intraoral herpes simplex virus, Wegener’s granulomatosis, oral Crohn’s disease, pyostomatitis vegetans, erythema multiforme, lichen planus, mucous membrane pemphigoid, and pemphigus vulgaris, he said.

A diffuse, widespread, and chronic presentation, which is not characteristic of recurrent aphthous stomatitis or Behçet’s, can help differentiate between those conditions and these differential diagnoses, he said.

Dr. Calamia disclosed that he has received research support from Genentech and Celgene, and has served on an advisory board for Centocor.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

BOCA RATON, FLA.– Androgenetic alopecia is fairly common in the pediatric population, and in adolescent girls it should prompt an evaluation for hyperandrogenism, according to Dr. Seth J. Orlow.

Androgenetic alopecia is a presenting symptom of polycystic ovary syndrome (PCOS) in a considerable number of cases, he said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery. "I think this is a place where we can really make a difference as dermatologists," said Dr. Orlow, chair of dermatology and professor of pediatric dermatology, cell biology, and pediatrics at New York University.

One of the most useful laboratory tests in adolescent girls presenting with early androgenetic alopecia is free and total testosterone, which at elevated levels can serve as a marker for PCOS.

"In a girl who presents with early-onset androgenetic alopecia, think about early presentation of PCOS. It’s definitely worth it to test them," he said.

A chart review of 438 consecutive pediatric patients with alopecia seen by Dr. Orlow and his colleagues over a 12-year period underscored the importance of looking for this diagnosis, and illustrated other characteristics of androgenetic alopecia in both girls and boys. The study showed that androgenetic alopecia was the second most common type of alopecia (after alopecia areata, which accounted for 55% of cases), involving 13% of the cases overall.

Among the 123 adolescent patients, however, 42% (52 patients: 36 boys and 16 girls) had androgenetic alopecia, for a total of 38 boys and 19 girls with androgenetic alopecia among the 438 studied.

Female Findings

Of the 19 girls, 9 had hyperandrogenism. Three had clinical signs and 6 had biochemical signs of hyperandrogenism. Of the six with biochemical signs, three had elevated free and total testosterone levels, one had elevated free and total testosterone and elevated dihydroepiandrosterone sulfate, one had an elevated free testosterone level only, and one had an elevated total testosterone level only

Seven of the girls were oligomenorrheic, and two were premenarchal. Clinical signs other than the androgenetic alopecia included hirsutism in four girls, acne in six, and seborrheic dermatitis in two.

Other laboratory findings in the 19 girls with androgenetic alopecia included antithyroid antibodies in 1of 5 tested and low serum iron in 3 of 14 tested. None of the girls tested had abnormal thyroid function, iron deficiency anemia, or low testosterone levels, Dr. Orlow said.

The most common presentations in girls were diffuse scalp thinning and thinning at the crown, each occurring in 8 of the 19 patients. The remaining three girls presented with frontal thinning only.

Male Findings

Findings in the boys presenting with androgenetic alopecia included antithyroid antibodies in 1 of 7 tested, hyperandrogenemia in 2 of 14 tested, and low testosterone levels in 3 of 14 tested. None of the boys had abnormal thyroid function, low serum iron, or iron deficiency anemia.

A disproportionate number of boys (13 of the 38) presented with classic female pattern androgenetic alopecia with diffuse thinning of the crown. The remaining boys presented with bitemporal vertex thinning (18 boys), vertex only thinning (4 boys), or frontal and vertex thinning (3 boys), Dr. Orlow said.

Concomitant findings included acne in 32% of the girls and 50% of the boys, and seborrheic dermatitis in 37% of the girls and 16% of the boys. A family history of androgenetic alopecia was present in both, with 82% of the boys and 87% of the girls having an affected first- or second-degree relative.

Differential Diagnoses

It is important to consider possible differential diagnoses in patients presenting with what appears to be androgenetic alopecia, Dr. Orlow said.

These include acute telogen effluvium, chronic telogen effluvium (particularly in girls), and diffuse alopecia areata.

If the clinical diagnosis is unclear – in boys with female pattern hair loss, in girls with very young onset, or if the patient or parents have a great deal of anxiety about the diagnosis – a biopsy may be helpful, he said.

Of the 57 patients with androgenetic alopecia included in his chart review, 14 (5 girls and 9 boys) underwent biopsy; all of the biopsies showed typical features of androgenetic alopecia, including increased vellus/telogen hairs and connective tissue streamers/follicular stelae below small vellus follicles.

Eight of the 14 also had varying degrees of peri-infundibular lymphocytic inflammatory infiltrate and fibrosis.

Treatment

Treatment options for patients with androgenetic alopecia include minoxidil, finasteride (in boys), and spironolactone.

Minoxidil was used in 16 of the 19 girls; 4 of 6 with greater than 6 months of follow-up had stabilized at 1 year. One developed increased facial hair on treatment, which resolved with a switch from a 5% to a 2% formulation, Dr. Orlow said.

Two patients discontinued treatment because of a lack of efficacy and/or headache and nausea.

In the boys, 36 of the 38 were treated with minoxidil, and 18 of 23 with at least 6 months of follow-up were stabilized. Two patients never started treatment and two discontinued for lack of efficacy and acne.

Finasteride was used in nine boys, including seven who also received minoxidil. In six boys, with at least 6 months of follow-up, all had better hair density (including four on concomitant minoxidil). One experienced sexual dysfunction, which resolved spontaneously, Dr. Orlow said.

"I did not treat – and would not treat girls [with finasteride], nor did I find any case reports of finasteride use in girls," he said.

There are a few case reports, however, of spironolactone being used in girls with some success, he noted.

The findings of the chart review (Br. J. Dermatol. 2010;163:378-85) underscore the importance of understanding that alopecia is a common complaint in the pediatric population, that androgenetic alopecia is the most common form of hair loss in adolescents, and that androgenetic alopecia can be a presenting sign of an underlying endocrine disorder, Dr. Orlow said.

He reported having no relevant financial disclosures.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.