Sharon Worcester

CHICAGO – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman.

“My goal is to give you some guidance when somebody asks, because what you're going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug,” said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet's syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, Dr. Ruderman noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab and infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet's uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one “nicely done” randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had “success,” which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%–29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis and asthma; findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized controlled trial of 231 patients with severe uncontrolled asthma. Those patients had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations and experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

“I don't know entirely what to make of that,” Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

CHICAGO – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman.

“My goal is to give you some guidance when somebody asks, because what you're going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug,” said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet's syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, Dr. Ruderman noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab and infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet's uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one “nicely done” randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had “success,” which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%–29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis and asthma; findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized controlled trial of 231 patients with severe uncontrolled asthma. Those patients had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations and experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

“I don't know entirely what to make of that,” Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

CHICAGO – The list of off-label uses for biologic agents is growing, and rheumatologists should stay abreast of even the nonrheumatologic uses, according to Dr. Eric Ruderman.

“My goal is to give you some guidance when somebody asks, because what you're going to find is that the dermatologists, ophthalmologists, and others are going to ask you as the rheumatologist, who is supposedly the expert in biologic therapy, what is the role for this, that, or the other drug,” said Dr. Ruderman, a rheumatologist at Northwestern University, Chicago.

There are scant data to support off-label uses, and these typically come from retrospective reports, small case series, or anecdotal experience, with a few exceptions, he said.

In dermatology, for example, infliximab is increasingly being used to treat hidradenitis suppurativa and neutrophilic dermatoses despite a lack of data from randomized controlled trials to support this practice. Findings from a small double-blind crossover trial involving 38 patients who were treated for 8 weeks, however, did suggest that infliximab improves pain, disease severity, and quality of life.

Some benefit was also shown with adalimumab in this disease in a recent case series, while benefits with etanercept were less clear in two open-label trials. Patients in the etanercept trials also had worsening of their condition after etanercept was discontinued.

As for neutrophilic dermatoses, infliximab appears to be useful for pyoderma gangrenosum and possibly for Sweet's syndrome. In a double-blind study of 30 patients with pyoderma gangrenosum, a single dose of 5 mg/kg was associated with a 46% improvement, compared with 6% for placebo. Furthermore, nonresponders on placebo at 2 weeks were treated with infliximab with a 60% response rate, and 21% of treated patients achieved remission.

Biologic therapies being used for ophthalmologic conditions include infliximab, adalimumab, and/or daclizumab for childhood uveitis and other types of uveitis, Dr. Ruderman noted.

Retrospective case series have shown benefit with infliximab, adalimumab, and daclizumab in childhood uveitis, and an open-label prospective study comparing adalimumab and infliximab demonstrated greater benefit with adalimumab (60% vs. 20% remission at 40 months), he said.

Infliximab also may have some benefit in ocular sarcoidosis, with case reports and small open-label series demonstrating some benefit. Etanercept in this disease, however, appears to be no more effective than placebo, based on findings of a randomized study of 18 patients treated for 6 months.

In Behçet's uveitis, case reports and findings from two small open trials suggest some benefit with infliximab. In the open trials, 9 of 12 patients responded to a dose of 5 mg/kg, Dr. Ruderman said, adding that treatment helped reduce steroid use, but relapse was frequent after treatment discontinuation, suggesting that ongoing therapy is necessary.

Other conditions in which biologics are currently being used include pulmonary and extrapulmonary sarcoidosis, asthma, and chronic obstructive pulmonary disease (COPD).

In one “nicely done” randomized, controlled, multicenter study of 138 pulmonary sarcoidosis patients, infliximab was superior to placebo for improving the percent predicted forced vital capacity at 24 weeks, and also led to improvement in extrapulmonary disease, Dr. Ruderman said.

Improvements in scores on the extrapulmonary physician organ severity tool (ePOST) were better in the treatment versus placebo group at 24 weeks, even after adjusting for the number of organs involved, he said.

Findings from an open-label study of etanercept in this disease, however, showed that only 5 of 17 patients had “success,” which was defined as lack of deterioration on x-rays or pulmonary function tests.

Case reports and retrospective data – but not randomized controlled data – have also shown some benefit of infliximab for cutaneous sarcoidosis. In 54 patients who received 116 courses of therapy, resolution or near resolution of lupus pernio was achieved in 77% of patients versus 11%–29% of those treated with steroids and other therapy. Some case reports show benefit in neurosarcoidosis, as well, but no solid data are available to back those up, Dr. Ruderman said.

For asthma, there may be a role for tumor necrosis factor inhibitors, although one randomized controlled trial showed no benefit with golimumab.

The Brigham RA Sequential Study, for example, demonstrated improvement with TNF inhibitors in nine patients with both rheumatoid arthritis and asthma; findings from a small, controlled trial of etanercept showed some benefit on several measures of response. The benefits in that study, however, were not clear-cut, and two other etanercept trials, as well as one infliximab trial, failed to show any benefit in asthma.

Similarly, golimumab showed no benefit in a 52-week randomized controlled trial of 231 patients with severe uncontrolled asthma. Those patients had no improvements over placebo in forced expiratory volume in 1 second (FEV₁) or exacerbations and experienced frequent severe infections, Dr. Ruderman said.

Two studies found that infliximab therapy provided no benefit in the management of COPD. The first was a 24-week study of 3 mg/kg, 5 mg/kg, and placebo in 159 patients. The findings showed no improvement in health status or FEV₁, no lessening of exacerbations with treatment vs. placebo, and an increase in the risk of pneumonia in the treated group. The second study was an observational study involving a cohort of 15,771 patients with both RA and COPD. In this study, however, treatment with etanercept was associated with a 50% reduction in the rate of COPD hospitalization.

“I don't know entirely what to make of that,” Dr. Ruderman said, adding that it might be a result of improvement in the RA and thus overall health.

Dr. Ruderman reported receiving consulting fees and/or research grants from Abbott, Allos, Amgen, Biogenidec, Celgene, Centocor, Crescendo, CVS/Caremark, Pfizer, and UCB.

CHICAGO – A number of treatments can be considered for cutaneous lupus erythematosus.

“Topicals are certainly a good way to start for a less severe patient,” Dr. Victoria P. Werth said at the meeting.

Topical steroids can be used, she said, noting that she often starts with a potent class 1 drug.

A class 1 drug, however, would be impossible to use on the face for more than a few days, added Dr. Werth, a dermatologist and immunologist at the University of Pennsylvania, Philadelphia.

“Often on the face we use Cortaid or something like a Synalar [fluocinolone] or Lidex [fluocinonide] for a short period of time and then taper down to hydrocortisone,” she said.

The more recently available topical nonsteroidal T-cell inhibitors, tacrolimus and pimecrolimus, can be used as adjunctive therapy. These agents aren't perfect, but they may be worth trying in a patient in whom one does not want to use steroids long term, she said.

Intralesional steroids are another treatment option and are particularly useful for scalp lesions and isolated lesions.

Vitamin D replacement also may be helpful. A study published last year showed that cutaneous lupus patients, like many people, had very low vitamin D levels in winter, but levels didn't rise much during the summer as they do in others – likely because patients are following advice about sun avoidance.

As for systemic therapy, data from prospective randomized controlled trials are lacking, and most guidance comes from retrospective case series. But antimalarials are considered first-line treatment in those who can't use topical therapy.

Specifically, hydroxychloroquine is typically given at 6.5 mg/kg per day or less for 6–8 weeks, and quinacrine can be added at 100 mg/day for an additional 6–8 weeks in those who fail to respond to hydroxychloroquine monotherapy.

Not everyone needs the combination, but it is very beneficial in some patients, Dr. Werth noted.

Chloroquine at 3.5 mg/kg per day can be used in those who fail to respond to that combination. Although there are more concerns about toxicity, there are patients who will do better on chloroquine, she said.

Other therapies beyond the topicals and antimalarials include dapsone, retinoids, thalidomide, methotrexate, mycophenolate mofetil, azathioprine, corticosteroids, and cyclophosphamide.

“We use dapsone predominantly for bullous lupus, and in some patients – if they're not too sick with their SLE, and their bullous lupus is not terrible – it's worth trying,” she said, noting that “it's very good on neutrophilic infiltrates, and it can work.”

Retinoids are on the list only because one trial compared them with antimalarials. Retinoids aren't very effective, they have a lot of toxicity, and they're not easy to use, she said.

In contrast, thalidomide can be very effective and is used in refractory patients. Its use is associated with rapid clinical response at 100 mg/day for 2 weeks, with full clinical response in 2–3 months. About 75% of patients who are refractory to antimalarials will respond.

Maintenance doses also can be effective (25–50 mg/day), but rapid relapse can occur on discontinuation.

Thalidomide does not have much effect on systemic lupus. Its use is associated with the risk for serious toxicity, including teratogenicity, neurotoxicity, premature ovarian failure, and hypercoagulable state.

Methotrexate, mycophenolate mofetil, and azathioprine have been shown to be equivalent to thalidomide in many ways, and because they aren't associated with the neurotoxicity that can occur with thalidomide, Dr. Werth said she often uses one of these first.

“I don't really have a preference for one over another,” she added.

She noted, however, that it is important to consider what else may be going on with patients, because those with renal involvement can be treated with mycophenolate mofetil or cyclophosphamide, and both may also help with cutaneous disease.

In addition to medical therapies, patients with cutaneous disease should be advised to avoid heat and drug exacerbations of their condition. It is critical that they use a high SPF sunscreen with good UVA and UVB coverage. Many sunscreens will say they offer both, but most don't have great UVA coverage, Dr. Werth said.

Tell patients to look for a product that has the highest SPF they can find (at least 30), and to ensure that the product contains ecamsule (Mexoryl) or avobenzone/oxybenzone (Helioplex) to provide good UVA protection, she advised.

Dr. Werth disclosed that she has received grants from Celgene Corporation and Amgen, and has served as a consultant to MedImmune, Genentech, Novartis, Pfizer, and Cephalon. She also developed an outcome measure for lupus.

CHICAGO – A number of treatments can be considered for cutaneous lupus erythematosus.

“Topicals are certainly a good way to start for a less severe patient,” Dr. Victoria P. Werth said at the meeting.

Topical steroids can be used, she said, noting that she often starts with a potent class 1 drug.

A class 1 drug, however, would be impossible to use on the face for more than a few days, added Dr. Werth, a dermatologist and immunologist at the University of Pennsylvania, Philadelphia.

“Often on the face we use Cortaid or something like a Synalar [fluocinolone] or Lidex [fluocinonide] for a short period of time and then taper down to hydrocortisone,” she said.

The more recently available topical nonsteroidal T-cell inhibitors, tacrolimus and pimecrolimus, can be used as adjunctive therapy. These agents aren't perfect, but they may be worth trying in a patient in whom one does not want to use steroids long term, she said.

Intralesional steroids are another treatment option and are particularly useful for scalp lesions and isolated lesions.

Vitamin D replacement also may be helpful. A study published last year showed that cutaneous lupus patients, like many people, had very low vitamin D levels in winter, but levels didn't rise much during the summer as they do in others – likely because patients are following advice about sun avoidance.

As for systemic therapy, data from prospective randomized controlled trials are lacking, and most guidance comes from retrospective case series. But antimalarials are considered first-line treatment in those who can't use topical therapy.

Specifically, hydroxychloroquine is typically given at 6.5 mg/kg per day or less for 6–8 weeks, and quinacrine can be added at 100 mg/day for an additional 6–8 weeks in those who fail to respond to hydroxychloroquine monotherapy.

Not everyone needs the combination, but it is very beneficial in some patients, Dr. Werth noted.

Chloroquine at 3.5 mg/kg per day can be used in those who fail to respond to that combination. Although there are more concerns about toxicity, there are patients who will do better on chloroquine, she said.

Other therapies beyond the topicals and antimalarials include dapsone, retinoids, thalidomide, methotrexate, mycophenolate mofetil, azathioprine, corticosteroids, and cyclophosphamide.

“We use dapsone predominantly for bullous lupus, and in some patients – if they're not too sick with their SLE, and their bullous lupus is not terrible – it's worth trying,” she said, noting that “it's very good on neutrophilic infiltrates, and it can work.”

Retinoids are on the list only because one trial compared them with antimalarials. Retinoids aren't very effective, they have a lot of toxicity, and they're not easy to use, she said.

In contrast, thalidomide can be very effective and is used in refractory patients. Its use is associated with rapid clinical response at 100 mg/day for 2 weeks, with full clinical response in 2–3 months. About 75% of patients who are refractory to antimalarials will respond.

Maintenance doses also can be effective (25–50 mg/day), but rapid relapse can occur on discontinuation.

Thalidomide does not have much effect on systemic lupus. Its use is associated with the risk for serious toxicity, including teratogenicity, neurotoxicity, premature ovarian failure, and hypercoagulable state.

Methotrexate, mycophenolate mofetil, and azathioprine have been shown to be equivalent to thalidomide in many ways, and because they aren't associated with the neurotoxicity that can occur with thalidomide, Dr. Werth said she often uses one of these first.

“I don't really have a preference for one over another,” she added.

She noted, however, that it is important to consider what else may be going on with patients, because those with renal involvement can be treated with mycophenolate mofetil or cyclophosphamide, and both may also help with cutaneous disease.

In addition to medical therapies, patients with cutaneous disease should be advised to avoid heat and drug exacerbations of their condition. It is critical that they use a high SPF sunscreen with good UVA and UVB coverage. Many sunscreens will say they offer both, but most don't have great UVA coverage, Dr. Werth said.

Tell patients to look for a product that has the highest SPF they can find (at least 30), and to ensure that the product contains ecamsule (Mexoryl) or avobenzone/oxybenzone (Helioplex) to provide good UVA protection, she advised.

Dr. Werth disclosed that she has received grants from Celgene Corporation and Amgen, and has served as a consultant to MedImmune, Genentech, Novartis, Pfizer, and Cephalon. She also developed an outcome measure for lupus.

CHICAGO – A number of treatments can be considered for cutaneous lupus erythematosus.

“Topicals are certainly a good way to start for a less severe patient,” Dr. Victoria P. Werth said at the meeting.

Topical steroids can be used, she said, noting that she often starts with a potent class 1 drug.

A class 1 drug, however, would be impossible to use on the face for more than a few days, added Dr. Werth, a dermatologist and immunologist at the University of Pennsylvania, Philadelphia.

“Often on the face we use Cortaid or something like a Synalar [fluocinolone] or Lidex [fluocinonide] for a short period of time and then taper down to hydrocortisone,” she said.

The more recently available topical nonsteroidal T-cell inhibitors, tacrolimus and pimecrolimus, can be used as adjunctive therapy. These agents aren't perfect, but they may be worth trying in a patient in whom one does not want to use steroids long term, she said.

Intralesional steroids are another treatment option and are particularly useful for scalp lesions and isolated lesions.

Vitamin D replacement also may be helpful. A study published last year showed that cutaneous lupus patients, like many people, had very low vitamin D levels in winter, but levels didn't rise much during the summer as they do in others – likely because patients are following advice about sun avoidance.

As for systemic therapy, data from prospective randomized controlled trials are lacking, and most guidance comes from retrospective case series. But antimalarials are considered first-line treatment in those who can't use topical therapy.

Specifically, hydroxychloroquine is typically given at 6.5 mg/kg per day or less for 6–8 weeks, and quinacrine can be added at 100 mg/day for an additional 6–8 weeks in those who fail to respond to hydroxychloroquine monotherapy.

Not everyone needs the combination, but it is very beneficial in some patients, Dr. Werth noted.

Chloroquine at 3.5 mg/kg per day can be used in those who fail to respond to that combination. Although there are more concerns about toxicity, there are patients who will do better on chloroquine, she said.

Other therapies beyond the topicals and antimalarials include dapsone, retinoids, thalidomide, methotrexate, mycophenolate mofetil, azathioprine, corticosteroids, and cyclophosphamide.

“We use dapsone predominantly for bullous lupus, and in some patients – if they're not too sick with their SLE, and their bullous lupus is not terrible – it's worth trying,” she said, noting that “it's very good on neutrophilic infiltrates, and it can work.”

Retinoids are on the list only because one trial compared them with antimalarials. Retinoids aren't very effective, they have a lot of toxicity, and they're not easy to use, she said.

In contrast, thalidomide can be very effective and is used in refractory patients. Its use is associated with rapid clinical response at 100 mg/day for 2 weeks, with full clinical response in 2–3 months. About 75% of patients who are refractory to antimalarials will respond.

Maintenance doses also can be effective (25–50 mg/day), but rapid relapse can occur on discontinuation.

Thalidomide does not have much effect on systemic lupus. Its use is associated with the risk for serious toxicity, including teratogenicity, neurotoxicity, premature ovarian failure, and hypercoagulable state.

Methotrexate, mycophenolate mofetil, and azathioprine have been shown to be equivalent to thalidomide in many ways, and because they aren't associated with the neurotoxicity that can occur with thalidomide, Dr. Werth said she often uses one of these first.

“I don't really have a preference for one over another,” she added.

She noted, however, that it is important to consider what else may be going on with patients, because those with renal involvement can be treated with mycophenolate mofetil or cyclophosphamide, and both may also help with cutaneous disease.

In addition to medical therapies, patients with cutaneous disease should be advised to avoid heat and drug exacerbations of their condition. It is critical that they use a high SPF sunscreen with good UVA and UVB coverage. Many sunscreens will say they offer both, but most don't have great UVA coverage, Dr. Werth said.

Tell patients to look for a product that has the highest SPF they can find (at least 30), and to ensure that the product contains ecamsule (Mexoryl) or avobenzone/oxybenzone (Helioplex) to provide good UVA protection, she advised.

Dr. Werth disclosed that she has received grants from Celgene Corporation and Amgen, and has served as a consultant to MedImmune, Genentech, Novartis, Pfizer, and Cephalon. She also developed an outcome measure for lupus.

CHICAGO – Rituximab is showing promise as an effective treatment for IgG4-related aortitis, a condition which has only recently been described.

In one patient with aortitis and a high serum IgG4 level of 1,560 mg/dL, treatment with rituximab resulted in a decrease to 390 mg/dL within 2 months. Currently the patient's serum IgG4 level is 26 mg/dL (normal is below 135 mg/dL), Dr. John H. Stone reported.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses, suggesting that the agent is depleting CD20-positive B cells that evolve into the short-lived plasma cells which produce this antibody, and thus making a good case that this process is pathologic, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital, Boston.

In another aortitis patient who had been treated with steroids but couldn't tolerate the side effects – and whose IgG4 levels increased when the steroids were discontinued – rituximab had an equally abrupt effect. At 1 month following treatment, her IgG4 levels had fallen to 31 mg/dL. And in a 68-year-old man who previously responded to steroids, but who flared and was being treated with various disease-modifying antirheumatic drugs, serial rituximab decreased his IgG4 level with each dose until it normalized.

Ten patients with aortitis, including seven with IgG4 elevation, have been treated with rituximab as part of this series, and IgG4 levels declined quickly in all seven, while all other IgG subclasses remained stable, he said.

IgG4-related aortitis was first described in 2009 by Dr. Stone and his colleagues, who published on the case of a 67-year-old patient who developed dissection of the ascending aorta in the setting of IgG4-related disease, thereby linking IgG4-related systemic disease with this newly recognized subset of noninfectious aortitis, and adding to a growing list of conditions, such as autoimmune pancreatitis, that are associated with IgG4-related systemic disease.

At surgery, a transmural lymphoplasmacytic infiltrate was detected in the aorta, and on immunohistochemical studies more than 50% of plasma cells in the lesion stained for IgG4. The patient's IgG4 levels were elevated nearly 10-fold, and reevaluation of a lymph node biopsy performed 4 years earlier showed previously undetected IgG4-related systemic disease (Arthritis Rheum. 2009;60:3139-45).

Dr. Stone and his colleagues concluded that IgG4-related systemic disease should be considered in all patients with aortitis of unknown etiology, and noted that treatment might prevent progression of the systemic disease to other organs.

At the ACR symposium, where he spoke on “odd types of vasculitis,” Dr. Stone said it is intriguing that this condition hadn't been previously identified given the number of other diagnoses known to be related to IgG4.

The findings prompted a review of prior cases of aortitis at Massachusetts General Hospital, where a large number of aortic surgeries are performed, and it was found that 5.2% of 638 thoracic aorta resections performed from 2003 through 2008 were inflammatory, and about 12% stained intensely for IgG4, he said.

“So we think [IgG4-related systemic disease] accounts for about 12% of cases of inflammatory aortitis,” he added, noting that in a 2008 study from Japan, 4 of 10 cases involving the descending aorta stained intensely for IgG4.

The findings demand that the classification of aortitis be revisited, and that lymphoplasmacytic IgG4-related disease be included as a type of isolated aortitis, Dr. Stone concluded.

Dr. Stone said that he had no relevant financial disclosures.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses.

Source DR. STONE

CHICAGO – Rituximab is showing promise as an effective treatment for IgG4-related aortitis, a condition which has only recently been described.

In one patient with aortitis and a high serum IgG4 level of 1,560 mg/dL, treatment with rituximab resulted in a decrease to 390 mg/dL within 2 months. Currently the patient's serum IgG4 level is 26 mg/dL (normal is below 135 mg/dL), Dr. John H. Stone reported.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses, suggesting that the agent is depleting CD20-positive B cells that evolve into the short-lived plasma cells which produce this antibody, and thus making a good case that this process is pathologic, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital, Boston.

In another aortitis patient who had been treated with steroids but couldn't tolerate the side effects – and whose IgG4 levels increased when the steroids were discontinued – rituximab had an equally abrupt effect. At 1 month following treatment, her IgG4 levels had fallen to 31 mg/dL. And in a 68-year-old man who previously responded to steroids, but who flared and was being treated with various disease-modifying antirheumatic drugs, serial rituximab decreased his IgG4 level with each dose until it normalized.

Ten patients with aortitis, including seven with IgG4 elevation, have been treated with rituximab as part of this series, and IgG4 levels declined quickly in all seven, while all other IgG subclasses remained stable, he said.

IgG4-related aortitis was first described in 2009 by Dr. Stone and his colleagues, who published on the case of a 67-year-old patient who developed dissection of the ascending aorta in the setting of IgG4-related disease, thereby linking IgG4-related systemic disease with this newly recognized subset of noninfectious aortitis, and adding to a growing list of conditions, such as autoimmune pancreatitis, that are associated with IgG4-related systemic disease.

At surgery, a transmural lymphoplasmacytic infiltrate was detected in the aorta, and on immunohistochemical studies more than 50% of plasma cells in the lesion stained for IgG4. The patient's IgG4 levels were elevated nearly 10-fold, and reevaluation of a lymph node biopsy performed 4 years earlier showed previously undetected IgG4-related systemic disease (Arthritis Rheum. 2009;60:3139-45).

Dr. Stone and his colleagues concluded that IgG4-related systemic disease should be considered in all patients with aortitis of unknown etiology, and noted that treatment might prevent progression of the systemic disease to other organs.

At the ACR symposium, where he spoke on “odd types of vasculitis,” Dr. Stone said it is intriguing that this condition hadn't been previously identified given the number of other diagnoses known to be related to IgG4.

The findings prompted a review of prior cases of aortitis at Massachusetts General Hospital, where a large number of aortic surgeries are performed, and it was found that 5.2% of 638 thoracic aorta resections performed from 2003 through 2008 were inflammatory, and about 12% stained intensely for IgG4, he said.

“So we think [IgG4-related systemic disease] accounts for about 12% of cases of inflammatory aortitis,” he added, noting that in a 2008 study from Japan, 4 of 10 cases involving the descending aorta stained intensely for IgG4.

The findings demand that the classification of aortitis be revisited, and that lymphoplasmacytic IgG4-related disease be included as a type of isolated aortitis, Dr. Stone concluded.

Dr. Stone said that he had no relevant financial disclosures.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses.

Source DR. STONE

CHICAGO – Rituximab is showing promise as an effective treatment for IgG4-related aortitis, a condition which has only recently been described.

In one patient with aortitis and a high serum IgG4 level of 1,560 mg/dL, treatment with rituximab resulted in a decrease to 390 mg/dL within 2 months. Currently the patient's serum IgG4 level is 26 mg/dL (normal is below 135 mg/dL), Dr. John H. Stone reported.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses, suggesting that the agent is depleting CD20-positive B cells that evolve into the short-lived plasma cells which produce this antibody, and thus making a good case that this process is pathologic, said Dr. Stone, director of clinical rheumatology at Massachusetts General Hospital, Boston.

In another aortitis patient who had been treated with steroids but couldn't tolerate the side effects – and whose IgG4 levels increased when the steroids were discontinued – rituximab had an equally abrupt effect. At 1 month following treatment, her IgG4 levels had fallen to 31 mg/dL. And in a 68-year-old man who previously responded to steroids, but who flared and was being treated with various disease-modifying antirheumatic drugs, serial rituximab decreased his IgG4 level with each dose until it normalized.

Ten patients with aortitis, including seven with IgG4 elevation, have been treated with rituximab as part of this series, and IgG4 levels declined quickly in all seven, while all other IgG subclasses remained stable, he said.

IgG4-related aortitis was first described in 2009 by Dr. Stone and his colleagues, who published on the case of a 67-year-old patient who developed dissection of the ascending aorta in the setting of IgG4-related disease, thereby linking IgG4-related systemic disease with this newly recognized subset of noninfectious aortitis, and adding to a growing list of conditions, such as autoimmune pancreatitis, that are associated with IgG4-related systemic disease.

At surgery, a transmural lymphoplasmacytic infiltrate was detected in the aorta, and on immunohistochemical studies more than 50% of plasma cells in the lesion stained for IgG4. The patient's IgG4 levels were elevated nearly 10-fold, and reevaluation of a lymph node biopsy performed 4 years earlier showed previously undetected IgG4-related systemic disease (Arthritis Rheum. 2009;60:3139-45).

Dr. Stone and his colleagues concluded that IgG4-related systemic disease should be considered in all patients with aortitis of unknown etiology, and noted that treatment might prevent progression of the systemic disease to other organs.

At the ACR symposium, where he spoke on “odd types of vasculitis,” Dr. Stone said it is intriguing that this condition hadn't been previously identified given the number of other diagnoses known to be related to IgG4.

The findings prompted a review of prior cases of aortitis at Massachusetts General Hospital, where a large number of aortic surgeries are performed, and it was found that 5.2% of 638 thoracic aorta resections performed from 2003 through 2008 were inflammatory, and about 12% stained intensely for IgG4, he said.

“So we think [IgG4-related systemic disease] accounts for about 12% of cases of inflammatory aortitis,” he added, noting that in a 2008 study from Japan, 4 of 10 cases involving the descending aorta stained intensely for IgG4.

The findings demand that the classification of aortitis be revisited, and that lymphoplasmacytic IgG4-related disease be included as a type of isolated aortitis, Dr. Stone concluded.

Dr. Stone said that he had no relevant financial disclosures.

Remarkably, the treatment appears to affect only IgG4 and not other IgG subclasses.

Source DR. STONE

DESTIN, FLA. – Although no agent has been approved for the treatment of Behçet's disease in the United States, several treatments have been tried in patients with mucocutaneous manifestations of the disease, said Dr. Kenneth Calamia.

Behçet's disease is relatively rare in the United States and Europe, occurring in 0.3 to 7.5 per 100,000 people, but among those affected, mucocutaneous symptoms are common, and in fact are among the hallmarks of the disease. In a study of 164 patients treated from 1985 to 1997 at the Mayo Clinic in Jacksonville, Fla., where Dr. Calamia is associate professor of medicine, 98% had oral ulcers and 80% had genital ulcers. These were the most common manifestations, he said.

According to 2008 EULAR guidelines for the treatment of Behçet's, the decision to treat skin and mucosal involvement should be based on the severity perceived by the physician and patient, and mucocutaneous involvement should be treated according to the dominant or codominant lesions present (Ann. Rheum. Dis. 2008;67:1656-62).

Topical treatments should be used first line for isolated oral and genital ulcers and acnelike lesions; colchicine should be used when the dominant lesion is erythema nodosum; and azathioprine, interferon-alpha, and tumor necrosis factor (TNF)-alpha antagonists can be considered in resistant cases, according to the guidelines.

The list of treatments used for the management of mucocutaneous manifestations includes these and other agents. One of Dr. Calamia's favorite concoctions for oral ulcers is “magic mouthwash,” an elixir of half Decadron (betamethasone) syrup or Celestone syrup and half Benadryl topical anesthetic. “This can control ulcerations very well, especially if used early at the first sign of a breakout,” he said. The elixir is used before meals and at bedtime, and is swished in the mouth, held as long as possible, and spit out.

According to Dr. Calamia, other treatments that have been used for mucocutaneous manifestations of Behçet's include topical steroids, which work and have a better side effect profile than do systemic treatments; topical tacrolimus, pimecrolimus, and pentoxifylline, which dermatologists particularly like; azathioprine, which works; interferon-alpha, which also works; thalidomide, which works but causes neuropathy, so it is no longer used for this disease; dapsone, which is another favorite of dermatologists; methotrexate, which is used but which he is “not personally impressed with” for mouth ulcers; colchicine, which can be used for this or any of the other manifestations of the disease; and anti-TNF agents, which are clearly of benefit.

In a randomized, placebo-controlled study of etanercept, 40% of 40 patients who received etanercept were ulcer free at 4 weeks, compared with just 5% of those who received placebo. There was a significant reduction in oral ulcers, modular lesions, skin lesions, and arthritis attacks at 4 weeks, he said (J. Rheum. 2005;32:98-105).

“There's no question that anti-TNF drugs do work, but it is probably best to try nonbiologics in these patients, especially for mucocutaneous disease,” said Dr. Calamia, who disclosed that he has received research support from Genentech and Celgene and served on an advisory board for Centocor.

DESTIN, FLA. – Although no agent has been approved for the treatment of Behçet's disease in the United States, several treatments have been tried in patients with mucocutaneous manifestations of the disease, said Dr. Kenneth Calamia.

Behçet's disease is relatively rare in the United States and Europe, occurring in 0.3 to 7.5 per 100,000 people, but among those affected, mucocutaneous symptoms are common, and in fact are among the hallmarks of the disease. In a study of 164 patients treated from 1985 to 1997 at the Mayo Clinic in Jacksonville, Fla., where Dr. Calamia is associate professor of medicine, 98% had oral ulcers and 80% had genital ulcers. These were the most common manifestations, he said.

According to 2008 EULAR guidelines for the treatment of Behçet's, the decision to treat skin and mucosal involvement should be based on the severity perceived by the physician and patient, and mucocutaneous involvement should be treated according to the dominant or codominant lesions present (Ann. Rheum. Dis. 2008;67:1656-62).

Topical treatments should be used first line for isolated oral and genital ulcers and acnelike lesions; colchicine should be used when the dominant lesion is erythema nodosum; and azathioprine, interferon-alpha, and tumor necrosis factor (TNF)-alpha antagonists can be considered in resistant cases, according to the guidelines.

The list of treatments used for the management of mucocutaneous manifestations includes these and other agents. One of Dr. Calamia's favorite concoctions for oral ulcers is “magic mouthwash,” an elixir of half Decadron (betamethasone) syrup or Celestone syrup and half Benadryl topical anesthetic. “This can control ulcerations very well, especially if used early at the first sign of a breakout,” he said. The elixir is used before meals and at bedtime, and is swished in the mouth, held as long as possible, and spit out.

According to Dr. Calamia, other treatments that have been used for mucocutaneous manifestations of Behçet's include topical steroids, which work and have a better side effect profile than do systemic treatments; topical tacrolimus, pimecrolimus, and pentoxifylline, which dermatologists particularly like; azathioprine, which works; interferon-alpha, which also works; thalidomide, which works but causes neuropathy, so it is no longer used for this disease; dapsone, which is another favorite of dermatologists; methotrexate, which is used but which he is “not personally impressed with” for mouth ulcers; colchicine, which can be used for this or any of the other manifestations of the disease; and anti-TNF agents, which are clearly of benefit.

In a randomized, placebo-controlled study of etanercept, 40% of 40 patients who received etanercept were ulcer free at 4 weeks, compared with just 5% of those who received placebo. There was a significant reduction in oral ulcers, modular lesions, skin lesions, and arthritis attacks at 4 weeks, he said (J. Rheum. 2005;32:98-105).

“There's no question that anti-TNF drugs do work, but it is probably best to try nonbiologics in these patients, especially for mucocutaneous disease,” said Dr. Calamia, who disclosed that he has received research support from Genentech and Celgene and served on an advisory board for Centocor.

DESTIN, FLA. – Although no agent has been approved for the treatment of Behçet's disease in the United States, several treatments have been tried in patients with mucocutaneous manifestations of the disease, said Dr. Kenneth Calamia.

Behçet's disease is relatively rare in the United States and Europe, occurring in 0.3 to 7.5 per 100,000 people, but among those affected, mucocutaneous symptoms are common, and in fact are among the hallmarks of the disease. In a study of 164 patients treated from 1985 to 1997 at the Mayo Clinic in Jacksonville, Fla., where Dr. Calamia is associate professor of medicine, 98% had oral ulcers and 80% had genital ulcers. These were the most common manifestations, he said.

According to 2008 EULAR guidelines for the treatment of Behçet's, the decision to treat skin and mucosal involvement should be based on the severity perceived by the physician and patient, and mucocutaneous involvement should be treated according to the dominant or codominant lesions present (Ann. Rheum. Dis. 2008;67:1656-62).

Topical treatments should be used first line for isolated oral and genital ulcers and acnelike lesions; colchicine should be used when the dominant lesion is erythema nodosum; and azathioprine, interferon-alpha, and tumor necrosis factor (TNF)-alpha antagonists can be considered in resistant cases, according to the guidelines.

The list of treatments used for the management of mucocutaneous manifestations includes these and other agents. One of Dr. Calamia's favorite concoctions for oral ulcers is “magic mouthwash,” an elixir of half Decadron (betamethasone) syrup or Celestone syrup and half Benadryl topical anesthetic. “This can control ulcerations very well, especially if used early at the first sign of a breakout,” he said. The elixir is used before meals and at bedtime, and is swished in the mouth, held as long as possible, and spit out.

According to Dr. Calamia, other treatments that have been used for mucocutaneous manifestations of Behçet's include topical steroids, which work and have a better side effect profile than do systemic treatments; topical tacrolimus, pimecrolimus, and pentoxifylline, which dermatologists particularly like; azathioprine, which works; interferon-alpha, which also works; thalidomide, which works but causes neuropathy, so it is no longer used for this disease; dapsone, which is another favorite of dermatologists; methotrexate, which is used but which he is “not personally impressed with” for mouth ulcers; colchicine, which can be used for this or any of the other manifestations of the disease; and anti-TNF agents, which are clearly of benefit.

In a randomized, placebo-controlled study of etanercept, 40% of 40 patients who received etanercept were ulcer free at 4 weeks, compared with just 5% of those who received placebo. There was a significant reduction in oral ulcers, modular lesions, skin lesions, and arthritis attacks at 4 weeks, he said (J. Rheum. 2005;32:98-105).

“There's no question that anti-TNF drugs do work, but it is probably best to try nonbiologics in these patients, especially for mucocutaneous disease,” said Dr. Calamia, who disclosed that he has received research support from Genentech and Celgene and 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 meeting.

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 the United States 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 disease, 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 meeting.

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 the United States 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 disease, 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 meeting.

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 the United States 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 disease, 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. – Opioid rotation is a common and potentially beneficial practice for helping to relieve chronic pain in patients who require ongoing opioid therapy, but there are very few data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, according to Dr. Perry Fine. 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, 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. If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he advised.

The second 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.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, consider an additional 10%–30% dose reduction, he said.

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.

Consider opioid rotation when benefits are inadequate despite dose increases.

Source ©Csaba Tóth/iStockphoto.com

Examples of Initial Dose Calculation

▸ 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 morphine 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 info. to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr 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).

Source: Dr. Fine

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 are very few data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, according to Dr. Perry Fine. 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, 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. If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he advised.

The second 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.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, consider an additional 10%–30% dose reduction, he said.

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.

Consider opioid rotation when benefits are inadequate despite dose increases.

Source ©Csaba Tóth/iStockphoto.com

Examples of Initial Dose Calculation

▸ 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 morphine 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 info. to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr 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).

Source: Dr. Fine

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 are very few data to guide best practice.

The recommended approach, therefore, is one that focuses on safety, according to Dr. Perry Fine. 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, 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. If an oral transmucosal fentanyl citrate formulation is used, start with the lowest dose, he advised.

The second 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.

In patients with specific vulnerabilities such as advanced age, renal insufficiency, or cognitive impairment, consider an additional 10%–30% dose reduction, he said.

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.

Consider opioid rotation when benefits are inadequate despite dose increases.

Source ©Csaba Tóth/iStockphoto.com

Examples of Initial Dose Calculation

▸ 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 morphine 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 info. to determine the oral equivalent dose of transdermal fentanyl (60 mg oral morphine = 25 mcg/hr 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).

Source: Dr. Fine

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, according to Dr. Perry G. Fine.

Among the benefits of the effective mu-opioid analgesic with N-methyl-

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.

Older patients or those with renal or hepatic problems need less frequent dosing and more cautious titration.

Source DR. FINE

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, according to Dr. Perry G. Fine.

Among the benefits of the effective mu-opioid analgesic with N-methyl-

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.

Older patients or those with renal or hepatic problems need less frequent dosing and more cautious titration.

Source DR. FINE

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, according to Dr. Perry G. Fine.

Among the benefits of the effective mu-opioid analgesic with N-methyl-

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.

Older patients or those with renal or hepatic problems need less frequent dosing and more cautious titration.

Source DR. FINE

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, acacording to Dr. Robert Inman.

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 Magnetic Resonance Imaging).

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.

A patient who has failed an anti-TNF is unlikely to respond to rituximab, despite its mechanism of action.

Source DR. INMAN

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, acacording to Dr. Robert Inman.

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 Magnetic Resonance Imaging).

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.

A patient who has failed an anti-TNF is unlikely to respond to rituximab, despite its mechanism of action.

Source DR. INMAN

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, acacording to Dr. Robert Inman.

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 Magnetic Resonance Imaging).

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.

A patient who has failed an anti-TNF is unlikely to respond to rituximab, despite its mechanism of action.

Source DR. INMAN

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. – 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.