Psoriasis

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble anti-TNF receptor therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three anti-TNF agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported.

The findings were published online on Dec. 21, 2010. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010.137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis "strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents," reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving anti-TNF agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took anti-TNF agents without developing opportunistic infections.

Patients had been treated with anti-TNF agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using reports from pharmaceutical companies, the investigators estimated a total of 57,711 patient-years of use of anti-TNF therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving anti-TNF agents as 152 per 100,000 patient-years, after adjusting for age and sex.

Differences in the incidence of opportunistic infection differed by anti-TNF agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). Because the opportunistic infections were rare, the confidence intervals were large and prevented statistical significance in comparisons.

Dr. Salmon-Ceron and her associates previously reported analyses of the same database showing that TB is the most common opportunistic infection in patients on anti-TNF agents, and that these therapies increased the risk for Legionella pneumophila pneumonia. They excluded those two infections from the current study to look at the risk for other infections.

The non-TB opportunistic infections were diverse and severe. Ten of the 43 patients required treatment in the intensive care unit, and 4 died. RATIO followed patients for 3 years from the diagnosis of opportunistic infection. An expert committee of three infectious disease specialists validated the diagnoses of opportunistic infection.

Bacterial infections accounted for a third of the opportunistic infections, including four with listeriosis, four with nocardiosis, four with atypical mycobacteriosis, and three with non-typhoid salmonellosis.

Of the 43 cases, 18 were viral infections, including 8 with severe herpes zoster, 3 with varicella, 3 with extensive herpes simplex, and 4 with disseminated cytomegalovirus infections.

In all, 10 cases were fungal infections, including 5 with pneumocystosis, 3 with invasive aspergillosis, and 2 with cryptococcosis.

Two cases were parasitic infections, both with leishmaniasis.

The anti-TNF therapy was stopped when opportunistic infection developed in all but one patient with pneumocystosis who remained on infliximab and recovered. Seventeen patients resumed anti-TNF therapy (usually the same one) after treating the opportunistic infection for a median of 1.7 months. Three relapses of opportunistic infections occurred, two among the 17 patients who resumed anti-TNF therapy and one among the 26 patients who did not restart anti-TNF agents.

Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Mèdicale).

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble anti-TNF receptor therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three anti-TNF agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported.

The findings were published online on Dec. 21, 2010. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010.137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis "strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents," reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving anti-TNF agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took anti-TNF agents without developing opportunistic infections.

Patients had been treated with anti-TNF agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using reports from pharmaceutical companies, the investigators estimated a total of 57,711 patient-years of use of anti-TNF therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving anti-TNF agents as 152 per 100,000 patient-years, after adjusting for age and sex.

Differences in the incidence of opportunistic infection differed by anti-TNF agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). Because the opportunistic infections were rare, the confidence intervals were large and prevented statistical significance in comparisons.

Dr. Salmon-Ceron and her associates previously reported analyses of the same database showing that TB is the most common opportunistic infection in patients on anti-TNF agents, and that these therapies increased the risk for Legionella pneumophila pneumonia. They excluded those two infections from the current study to look at the risk for other infections.

The non-TB opportunistic infections were diverse and severe. Ten of the 43 patients required treatment in the intensive care unit, and 4 died. RATIO followed patients for 3 years from the diagnosis of opportunistic infection. An expert committee of three infectious disease specialists validated the diagnoses of opportunistic infection.

Bacterial infections accounted for a third of the opportunistic infections, including four with listeriosis, four with nocardiosis, four with atypical mycobacteriosis, and three with non-typhoid salmonellosis.

Of the 43 cases, 18 were viral infections, including 8 with severe herpes zoster, 3 with varicella, 3 with extensive herpes simplex, and 4 with disseminated cytomegalovirus infections.

In all, 10 cases were fungal infections, including 5 with pneumocystosis, 3 with invasive aspergillosis, and 2 with cryptococcosis.

Two cases were parasitic infections, both with leishmaniasis.

The anti-TNF therapy was stopped when opportunistic infection developed in all but one patient with pneumocystosis who remained on infliximab and recovered. Seventeen patients resumed anti-TNF therapy (usually the same one) after treating the opportunistic infection for a median of 1.7 months. Three relapses of opportunistic infections occurred, two among the 17 patients who resumed anti-TNF therapy and one among the 26 patients who did not restart anti-TNF agents.

Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Mèdicale).

Patients taking monoclonal anti–tumor necrosis factor antibody therapy were more likely than those on soluble anti-TNF receptor therapy to develop opportunistic infections, other than tuberculosis, in a study of a French national registry.

Of the three anti-TNF agents used in France in 2004-2007, infliximab was associated with an 18-fold increased risk and adalimumab was associated with a 10-fold increased risk for nontuberculosis opportunistic infection, compared with etanercept, Dr. Dominique Salmon-Ceron and her associates reported.

The findings were published online on Dec. 21, 2010. A higher incidence of opportunistic infection with infliximab or adalimumab, compared with etanercept, did not reach statistical significance because of the rarity of the infections. But the findings are supported by previous reports from the Food and Drug Administration, a Spanish registry, a study of 21 Japanese patients, and other accounts of a greater risk for opportunistic infection with infliximab, compared with etanercept, the investigators noted (Ann. Rheum. Dis. 2010 Dec. 21 [doi:10.1136/ard.2010.137422]).

The study also identified a third risk factor: treatment with more than 10 mg/day of oral steroids or IV steroid boluses during the year before a diagnosis of non-TB opportunistic infection. Previous studies also identified this risk factor in patients with rheumatoid arthritis or systemic lupus erythematosus, so the current analysis "strengthens the need to avoid high doses of steroids for patients receiving anti-TNF agents," reported Dr. Salmon-Ceron, who is professor of infectious diseases at Université René Descartes, Paris, as well as a member of the staff at of Hôpital Cochin in that city.

The data in the study come from the 3-year French RATIO (Research Axed on Tolerance of Biotherapies) registry and involved all cases in France of opportunistic infections in patients receiving anti-TNF agents for any reason. The case-control analysis matched each of the 43 case patients (with a total of 45 opportunistic infections) with 3 control patients who took anti-TNF agents without developing opportunistic infections.

Patients had been treated with anti-TNF agents for RA (26), spondyloarthritides (3), inflammatory colitis (8), psoriasis (1), or other problems (5). Four were on etanercept, 10 received adalimumab, and 39 were on infliximab.

Using reports from pharmaceutical companies, the investigators estimated a total of 57,711 patient-years of use of anti-TNF therapy during the study period. They calculated an annual incidence of opportunistic infection in patients receiving anti-TNF agents as 152 per 100,000 patient-years, after adjusting for age and sex.

Differences in the incidence of opportunistic infection differed by anti-TNF agent, but the differences were not statistically significant (7 per 100,000 patient-years with etanercept, 62 per 100,000 patient-years with adalimumab, and 291 per 100,000 patient-years with infliximab). Because the opportunistic infections were rare, the confidence intervals were large and prevented statistical significance in comparisons.

Dr. Salmon-Ceron and her associates previously reported analyses of the same database showing that TB is the most common opportunistic infection in patients on anti-TNF agents, and that these therapies increased the risk for Legionella pneumophila pneumonia. They excluded those two infections from the current study to look at the risk for other infections.

The non-TB opportunistic infections were diverse and severe. Ten of the 43 patients required treatment in the intensive care unit, and 4 died. RATIO followed patients for 3 years from the diagnosis of opportunistic infection. An expert committee of three infectious disease specialists validated the diagnoses of opportunistic infection.

Bacterial infections accounted for a third of the opportunistic infections, including four with listeriosis, four with nocardiosis, four with atypical mycobacteriosis, and three with non-typhoid salmonellosis.

Of the 43 cases, 18 were viral infections, including 8 with severe herpes zoster, 3 with varicella, 3 with extensive herpes simplex, and 4 with disseminated cytomegalovirus infections.

In all, 10 cases were fungal infections, including 5 with pneumocystosis, 3 with invasive aspergillosis, and 2 with cryptococcosis.

Two cases were parasitic infections, both with leishmaniasis.

The anti-TNF therapy was stopped when opportunistic infection developed in all but one patient with pneumocystosis who remained on infliximab and recovered. Seventeen patients resumed anti-TNF therapy (usually the same one) after treating the opportunistic infection for a median of 1.7 months. Three relapses of opportunistic infections occurred, two among the 17 patients who resumed anti-TNF therapy and one among the 26 patients who did not restart anti-TNF agents.

Some of Dr. Salmon-Ceron's coauthors have been consultants or speakers for Abbott, Schering Plough, UCB, or Wyeth. The study was funded by Abbott, Schering Plough, Wyeth, and INSERM (Institut National de la Santé et de la Recherche Mèdicale).

LAS VEGAS - Dermatologists may be doing patients with psoriasis a disservice if they don’t prescribe a good anti-inflammatory drug to reduce the risk of MI, according to Dr. Bruce E. Strober.

People with psoriasis are more likely to have comorbidities and behaviors associated with cardiovascular disease including smoking, alcohol misuse, hypertension, diabetes, dyslipidemia, and obesity. Dyslipidemia therapies that patients with psoriasis may take such as corticosteroids, acitretin, and cyclosporine can also increase cardiovascular risk.

Aside from these, psoriasis is independently associated with a higher risk for MI, stroke and death, probably due to the cardiovascular effects of uncontrolled inflammation, Dr. Strober said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

"You might say to a patient, this is a disease that has every bit as much an effect as hypertension on mortality. The data on hypertension are not even as impressive as this," said Dr. Strober of the department of dermatology at New York University. "Maybe this is a big deal that cardiologists need to think about. They are starting to catch on."

Rheumatoid arthritis studies show that methotrexate and tumor necrosis factor blockers reduce comorbid risks, and the same may be true for psoriasis. "That’s why I sometimes say methotrexate may have an overall net benefit when given to patients with severe psoriasis," he said. Any potential toxicity from methotrexate should be weighed against its potential cardiovascular advantages. A prospective, British population–based cohort study found that the incidence of MI was 3.6 per 1,000 patient-years among 556,995 control patients without psoriasis, 4.0 among 127,139 patients with mild psoriasis, and 5.1 among 3,837 patients with severe psoriasis after controlling for other cardiovascular risk factors (JAMA 2006;296:1735-41).

Younger patients with severe psoriasis had the greatest risk. The relative risk for MI with mild psoriasis was 1.3 in 30-year-olds and 1.1 in 60-year-olds. The relative risk for MI with severe psoriasis was 3.1 for 30-year-olds and 1.4 for 60-year-olds.

The study may have underestimated the cardiovascular risk of severe psoriasis by limiting the definition of severe disease to patients on systemic therapy, Dr. Strober added. Some with severe disease may have been assigned to the mild psoriasis category.

The most likely cause of this increased risk for MI is uncontrolled inflammation in systemic psoriasis, not unlike rheumatoid arthritis and lupus, which also are known to create MI risk, he said. Psoriasis has immune effects and creates a hyperinflammatory state. Uncontrolled inflammation leads to endothelial dysfunction and dyslipidemia.

A separate study of the same British database found that women and men with psoriasis died 3.5 years and 4.4 years, respectively, earlier than people without psoriasis after controlling for other risk factors for mortality (Arch. Dermatol. 2007;143:1493-99).

Other data sets have substantiated this concept in the Medicare population. "People with psoriasis die younger. We have to think of this as a disease that has a direct effect on mortality," Dr. Strober said.

Will dermatologists accept the role of primary screeners for comorbidities that increase the risk for cardiovascular disease and other problems? That remains to be seen, but the National Psoriasis Foundation’s 2008 clinical consensus statement provided guidance for dermatologists willing to screen (J. Am. Acad. Dermatol. 2008;58:1031-42).

Basic screening steps include assessing blood pressure and overweight or obese status and getting laboratory evaluations – a fasting comprehensive metabolic panel and fasting lipids. Physicians also should ask about use of alcohol, smoking, depression, and arthritis.

Comorbidities may make it harder to treat psoriasis, and vice versa, though data are sparse, Dr. Strober said. Obese patients, for example, may need larger doses of psoriasis medications. The hyperinflammatory state of psoriasis may make treating psoriasis difficult unless it's addressed, and conceivably make it more difficult to treat hypertension or dyslipidemia, but this has not been studied, he said.

Dr. Strober has received grants from or been a consultant, speaker or advisor for Abbott, Amgen, Centocor, Johnson & Johnson, Pfizer, and Celgene.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS - Dermatologists may be doing patients with psoriasis a disservice if they don’t prescribe a good anti-inflammatory drug to reduce the risk of MI, according to Dr. Bruce E. Strober.

People with psoriasis are more likely to have comorbidities and behaviors associated with cardiovascular disease including smoking, alcohol misuse, hypertension, diabetes, dyslipidemia, and obesity. Dyslipidemia therapies that patients with psoriasis may take such as corticosteroids, acitretin, and cyclosporine can also increase cardiovascular risk.

Aside from these, psoriasis is independently associated with a higher risk for MI, stroke and death, probably due to the cardiovascular effects of uncontrolled inflammation, Dr. Strober said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

"You might say to a patient, this is a disease that has every bit as much an effect as hypertension on mortality. The data on hypertension are not even as impressive as this," said Dr. Strober of the department of dermatology at New York University. "Maybe this is a big deal that cardiologists need to think about. They are starting to catch on."

Rheumatoid arthritis studies show that methotrexate and tumor necrosis factor blockers reduce comorbid risks, and the same may be true for psoriasis. "That’s why I sometimes say methotrexate may have an overall net benefit when given to patients with severe psoriasis," he said. Any potential toxicity from methotrexate should be weighed against its potential cardiovascular advantages. A prospective, British population–based cohort study found that the incidence of MI was 3.6 per 1,000 patient-years among 556,995 control patients without psoriasis, 4.0 among 127,139 patients with mild psoriasis, and 5.1 among 3,837 patients with severe psoriasis after controlling for other cardiovascular risk factors (JAMA 2006;296:1735-41).

Younger patients with severe psoriasis had the greatest risk. The relative risk for MI with mild psoriasis was 1.3 in 30-year-olds and 1.1 in 60-year-olds. The relative risk for MI with severe psoriasis was 3.1 for 30-year-olds and 1.4 for 60-year-olds.

The study may have underestimated the cardiovascular risk of severe psoriasis by limiting the definition of severe disease to patients on systemic therapy, Dr. Strober added. Some with severe disease may have been assigned to the mild psoriasis category.

The most likely cause of this increased risk for MI is uncontrolled inflammation in systemic psoriasis, not unlike rheumatoid arthritis and lupus, which also are known to create MI risk, he said. Psoriasis has immune effects and creates a hyperinflammatory state. Uncontrolled inflammation leads to endothelial dysfunction and dyslipidemia.

A separate study of the same British database found that women and men with psoriasis died 3.5 years and 4.4 years, respectively, earlier than people without psoriasis after controlling for other risk factors for mortality (Arch. Dermatol. 2007;143:1493-99).

Other data sets have substantiated this concept in the Medicare population. "People with psoriasis die younger. We have to think of this as a disease that has a direct effect on mortality," Dr. Strober said.

Will dermatologists accept the role of primary screeners for comorbidities that increase the risk for cardiovascular disease and other problems? That remains to be seen, but the National Psoriasis Foundation’s 2008 clinical consensus statement provided guidance for dermatologists willing to screen (J. Am. Acad. Dermatol. 2008;58:1031-42).

Basic screening steps include assessing blood pressure and overweight or obese status and getting laboratory evaluations – a fasting comprehensive metabolic panel and fasting lipids. Physicians also should ask about use of alcohol, smoking, depression, and arthritis.

Comorbidities may make it harder to treat psoriasis, and vice versa, though data are sparse, Dr. Strober said. Obese patients, for example, may need larger doses of psoriasis medications. The hyperinflammatory state of psoriasis may make treating psoriasis difficult unless it's addressed, and conceivably make it more difficult to treat hypertension or dyslipidemia, but this has not been studied, he said.

Dr. Strober has received grants from or been a consultant, speaker or advisor for Abbott, Amgen, Centocor, Johnson & Johnson, Pfizer, and Celgene.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS - Dermatologists may be doing patients with psoriasis a disservice if they don’t prescribe a good anti-inflammatory drug to reduce the risk of MI, according to Dr. Bruce E. Strober.

People with psoriasis are more likely to have comorbidities and behaviors associated with cardiovascular disease including smoking, alcohol misuse, hypertension, diabetes, dyslipidemia, and obesity. Dyslipidemia therapies that patients with psoriasis may take such as corticosteroids, acitretin, and cyclosporine can also increase cardiovascular risk.

Aside from these, psoriasis is independently associated with a higher risk for MI, stroke and death, probably due to the cardiovascular effects of uncontrolled inflammation, Dr. Strober said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

"You might say to a patient, this is a disease that has every bit as much an effect as hypertension on mortality. The data on hypertension are not even as impressive as this," said Dr. Strober of the department of dermatology at New York University. "Maybe this is a big deal that cardiologists need to think about. They are starting to catch on."

Rheumatoid arthritis studies show that methotrexate and tumor necrosis factor blockers reduce comorbid risks, and the same may be true for psoriasis. "That’s why I sometimes say methotrexate may have an overall net benefit when given to patients with severe psoriasis," he said. Any potential toxicity from methotrexate should be weighed against its potential cardiovascular advantages. A prospective, British population–based cohort study found that the incidence of MI was 3.6 per 1,000 patient-years among 556,995 control patients without psoriasis, 4.0 among 127,139 patients with mild psoriasis, and 5.1 among 3,837 patients with severe psoriasis after controlling for other cardiovascular risk factors (JAMA 2006;296:1735-41).

Younger patients with severe psoriasis had the greatest risk. The relative risk for MI with mild psoriasis was 1.3 in 30-year-olds and 1.1 in 60-year-olds. The relative risk for MI with severe psoriasis was 3.1 for 30-year-olds and 1.4 for 60-year-olds.

The study may have underestimated the cardiovascular risk of severe psoriasis by limiting the definition of severe disease to patients on systemic therapy, Dr. Strober added. Some with severe disease may have been assigned to the mild psoriasis category.

The most likely cause of this increased risk for MI is uncontrolled inflammation in systemic psoriasis, not unlike rheumatoid arthritis and lupus, which also are known to create MI risk, he said. Psoriasis has immune effects and creates a hyperinflammatory state. Uncontrolled inflammation leads to endothelial dysfunction and dyslipidemia.

A separate study of the same British database found that women and men with psoriasis died 3.5 years and 4.4 years, respectively, earlier than people without psoriasis after controlling for other risk factors for mortality (Arch. Dermatol. 2007;143:1493-99).

Other data sets have substantiated this concept in the Medicare population. "People with psoriasis die younger. We have to think of this as a disease that has a direct effect on mortality," Dr. Strober said.

Will dermatologists accept the role of primary screeners for comorbidities that increase the risk for cardiovascular disease and other problems? That remains to be seen, but the National Psoriasis Foundation’s 2008 clinical consensus statement provided guidance for dermatologists willing to screen (J. Am. Acad. Dermatol. 2008;58:1031-42).

Basic screening steps include assessing blood pressure and overweight or obese status and getting laboratory evaluations – a fasting comprehensive metabolic panel and fasting lipids. Physicians also should ask about use of alcohol, smoking, depression, and arthritis.

Comorbidities may make it harder to treat psoriasis, and vice versa, though data are sparse, Dr. Strober said. Obese patients, for example, may need larger doses of psoriasis medications. The hyperinflammatory state of psoriasis may make treating psoriasis difficult unless it's addressed, and conceivably make it more difficult to treat hypertension or dyslipidemia, but this has not been studied, he said.

Dr. Strober has received grants from or been a consultant, speaker or advisor for Abbott, Amgen, Centocor, Johnson & Johnson, Pfizer, and Celgene.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Immunosuppressive drug therapy is not an absolute contraindication for allergy patch testing, according to Dr. Joseph F. Fowler Jr.

A recent report on 11 patients who underwent patch testing while on a variety of systemic immunosuppressive drugs suggested patch testing may be more successful than many clinicians think, Dr. Fowler said. Speaking at the seminar sponsored by Skin Disease Education Foundation (SDEF), he fleshed out the findings with advice from his own experience in patch testing patients on immunosuppressives.

The retrospective chart review included patients on prednisone, cyclosporine, mycophenolate mofetil, or infliximab (Dermatitis 2009;20:265-70).

All but one of the patients who were taking 10 mg/day of prednisone had positive patch test reactions, said Dr. Fowler of the University of Louisville (Ky.) and president of the North American Contact Dermatitis Group.

"In the past, we had thought that about 10 mg/day was the maximum" prednisone dose that could still allow successful patch testing, but this belief was based on extrapolations of animal studies and case reports, with no hard data, he said. "I have personally seen patients who are on higher doses of prednisone produce good positive reactions."

Ideally, though, it’s best to patch test when patients are off prednisone, or on doses of 10 mg/day or less, he added. "If you could get them on every-other-day prednisone dosing, that would be even better."

For an untreated patient with fairly bad dermatitis, especially on the back, Dr. Fowler may treat for 5-7 days with a corticosteroid, perhaps prednisone 40-60 mg/day with no taper, and then stop the corticosteroid for 2-3 days before patch testing. "That’s one way you can get a person clear enough to patch test them if they’re already broken out," he said.

If the patient already is on chronic corticosteroid therapy, he tries to reduce the dose to 10 mg/day or less for several weeks before patch testing.

Dr. Fowler was surprised patients in the report who were being treated with cyclosporine 200 or 300 mg/day all had positive reactions to patch testing. "Generally, we expect cyclosporine to reduce the likelihood of positive reactions because of its broad immunosuppressant effect," he said. "These folks were on relatively low doses, so maybe that was a factor." In his own experience, Dr. Fowler said he has rarely seen positive reactions to patch testing in patients on cyclosporine, "so I think that’s problematic," he added.

One patient on mycophenolate (CellCept) 2 g/day had a negative result when patch tested but then stopped the drug and had a positive reaction on repeat patch testing. "That would suggest that the CellCept suppressed reactions," Dr. Fowler said. He advised not patch testing patients who are on CellCept, cyclosporine, tacrolimus, or azathioprine if at all possible.

One patient on infliximab (Remicade) whose last infusion occurred 3 weeks before patch testing developed multiple positive reactions. "That mirrors what I’ve been perceiving in clinical practice," he said.

Use of methotrexate or tumor necrosis factor–alpha inhibitors such as Remicade or etanercept (Enbrel) should not prevent patch testing. "I’ve had no problem patch testing people on methotrexate," Dr. Fowler said.

The report did not include antihistamines, which also are not a barrier to patch testing. "Other docs, allergists especially, tell patients they can’t take antihistamines when they’re being patch tested," he explained. "They may not be able to take antihistamines and get a good scratch test result, but remember in patch testing you’re looking at a T cell–mediated process. Antihistamines have essentially no effect on that."

Dr. Fowler has been a consultant, speaker, or researcher for Coria, Galderma, Graceway, Hyland, Johnson & Johnson, Quinnova, Ranbaxy, Shire, Stiefel, Triax, UCB, Medicis, Novartis, Abbott, Taro, Allerderm, Allergan, Amgen, Astellas, Centocor, Dermik, Dow, Genentech, Taisho, and 3M.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Immunosuppressive drug therapy is not an absolute contraindication for allergy patch testing, according to Dr. Joseph F. Fowler Jr.

A recent report on 11 patients who underwent patch testing while on a variety of systemic immunosuppressive drugs suggested patch testing may be more successful than many clinicians think, Dr. Fowler said. Speaking at the seminar sponsored by Skin Disease Education Foundation (SDEF), he fleshed out the findings with advice from his own experience in patch testing patients on immunosuppressives.

The retrospective chart review included patients on prednisone, cyclosporine, mycophenolate mofetil, or infliximab (Dermatitis 2009;20:265-70).

All but one of the patients who were taking 10 mg/day of prednisone had positive patch test reactions, said Dr. Fowler of the University of Louisville (Ky.) and president of the North American Contact Dermatitis Group.

"In the past, we had thought that about 10 mg/day was the maximum" prednisone dose that could still allow successful patch testing, but this belief was based on extrapolations of animal studies and case reports, with no hard data, he said. "I have personally seen patients who are on higher doses of prednisone produce good positive reactions."

Ideally, though, it’s best to patch test when patients are off prednisone, or on doses of 10 mg/day or less, he added. "If you could get them on every-other-day prednisone dosing, that would be even better."

For an untreated patient with fairly bad dermatitis, especially on the back, Dr. Fowler may treat for 5-7 days with a corticosteroid, perhaps prednisone 40-60 mg/day with no taper, and then stop the corticosteroid for 2-3 days before patch testing. "That’s one way you can get a person clear enough to patch test them if they’re already broken out," he said.

If the patient already is on chronic corticosteroid therapy, he tries to reduce the dose to 10 mg/day or less for several weeks before patch testing.

Dr. Fowler was surprised patients in the report who were being treated with cyclosporine 200 or 300 mg/day all had positive reactions to patch testing. "Generally, we expect cyclosporine to reduce the likelihood of positive reactions because of its broad immunosuppressant effect," he said. "These folks were on relatively low doses, so maybe that was a factor." In his own experience, Dr. Fowler said he has rarely seen positive reactions to patch testing in patients on cyclosporine, "so I think that’s problematic," he added.

One patient on mycophenolate (CellCept) 2 g/day had a negative result when patch tested but then stopped the drug and had a positive reaction on repeat patch testing. "That would suggest that the CellCept suppressed reactions," Dr. Fowler said. He advised not patch testing patients who are on CellCept, cyclosporine, tacrolimus, or azathioprine if at all possible.

One patient on infliximab (Remicade) whose last infusion occurred 3 weeks before patch testing developed multiple positive reactions. "That mirrors what I’ve been perceiving in clinical practice," he said.

Use of methotrexate or tumor necrosis factor–alpha inhibitors such as Remicade or etanercept (Enbrel) should not prevent patch testing. "I’ve had no problem patch testing people on methotrexate," Dr. Fowler said.

The report did not include antihistamines, which also are not a barrier to patch testing. "Other docs, allergists especially, tell patients they can’t take antihistamines when they’re being patch tested," he explained. "They may not be able to take antihistamines and get a good scratch test result, but remember in patch testing you’re looking at a T cell–mediated process. Antihistamines have essentially no effect on that."

Dr. Fowler has been a consultant, speaker, or researcher for Coria, Galderma, Graceway, Hyland, Johnson & Johnson, Quinnova, Ranbaxy, Shire, Stiefel, Triax, UCB, Medicis, Novartis, Abbott, Taro, Allerderm, Allergan, Amgen, Astellas, Centocor, Dermik, Dow, Genentech, Taisho, and 3M.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Immunosuppressive drug therapy is not an absolute contraindication for allergy patch testing, according to Dr. Joseph F. Fowler Jr.

A recent report on 11 patients who underwent patch testing while on a variety of systemic immunosuppressive drugs suggested patch testing may be more successful than many clinicians think, Dr. Fowler said. Speaking at the seminar sponsored by Skin Disease Education Foundation (SDEF), he fleshed out the findings with advice from his own experience in patch testing patients on immunosuppressives.

The retrospective chart review included patients on prednisone, cyclosporine, mycophenolate mofetil, or infliximab (Dermatitis 2009;20:265-70).

All but one of the patients who were taking 10 mg/day of prednisone had positive patch test reactions, said Dr. Fowler of the University of Louisville (Ky.) and president of the North American Contact Dermatitis Group.

"In the past, we had thought that about 10 mg/day was the maximum" prednisone dose that could still allow successful patch testing, but this belief was based on extrapolations of animal studies and case reports, with no hard data, he said. "I have personally seen patients who are on higher doses of prednisone produce good positive reactions."

Ideally, though, it’s best to patch test when patients are off prednisone, or on doses of 10 mg/day or less, he added. "If you could get them on every-other-day prednisone dosing, that would be even better."

For an untreated patient with fairly bad dermatitis, especially on the back, Dr. Fowler may treat for 5-7 days with a corticosteroid, perhaps prednisone 40-60 mg/day with no taper, and then stop the corticosteroid for 2-3 days before patch testing. "That’s one way you can get a person clear enough to patch test them if they’re already broken out," he said.

If the patient already is on chronic corticosteroid therapy, he tries to reduce the dose to 10 mg/day or less for several weeks before patch testing.

Dr. Fowler was surprised patients in the report who were being treated with cyclosporine 200 or 300 mg/day all had positive reactions to patch testing. "Generally, we expect cyclosporine to reduce the likelihood of positive reactions because of its broad immunosuppressant effect," he said. "These folks were on relatively low doses, so maybe that was a factor." In his own experience, Dr. Fowler said he has rarely seen positive reactions to patch testing in patients on cyclosporine, "so I think that’s problematic," he added.

One patient on mycophenolate (CellCept) 2 g/day had a negative result when patch tested but then stopped the drug and had a positive reaction on repeat patch testing. "That would suggest that the CellCept suppressed reactions," Dr. Fowler said. He advised not patch testing patients who are on CellCept, cyclosporine, tacrolimus, or azathioprine if at all possible.

One patient on infliximab (Remicade) whose last infusion occurred 3 weeks before patch testing developed multiple positive reactions. "That mirrors what I’ve been perceiving in clinical practice," he said.

Use of methotrexate or tumor necrosis factor–alpha inhibitors such as Remicade or etanercept (Enbrel) should not prevent patch testing. "I’ve had no problem patch testing people on methotrexate," Dr. Fowler said.

The report did not include antihistamines, which also are not a barrier to patch testing. "Other docs, allergists especially, tell patients they can’t take antihistamines when they’re being patch tested," he explained. "They may not be able to take antihistamines and get a good scratch test result, but remember in patch testing you’re looking at a T cell–mediated process. Antihistamines have essentially no effect on that."

Dr. Fowler has been a consultant, speaker, or researcher for Coria, Galderma, Graceway, Hyland, Johnson & Johnson, Quinnova, Ranbaxy, Shire, Stiefel, Triax, UCB, Medicis, Novartis, Abbott, Taro, Allerderm, Allergan, Amgen, Astellas, Centocor, Dermik, Dow, Genentech, Taisho, and 3M.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS - Practical phototherapy means not thinking strictly in terms of protocols, according to Dr. Kenneth B. Gordon.

Many protocols have been published for psoriasis phototherapy, and good ones were published by the American Academy of Dermatology in early 2010 (J. Amer. Acad. Dermatol. 2010;62:114-35), said Dr. Gordon of the University of Chicago. The guidelines emphasize tailoring therapy to meet the individual patient’s needs, and physicians should consider the best treatment for each patient.

"Simple, published protocols are not sufficient if you really do phototherapy," Dr. Gordon said.

He challenged the audience members with a quiz to test their knowledge of practical phototherapy in particular cases. The cases excluded patients with psoriatic arthritis.

"There are no right answers to these questions," Dr. Gordon said. "There are some wrong answers to these questions, however."

The Quiz Cases

– Case 1: What method of phototherapy would you use to treat a young woman with limited plaque psoriasis, primarily on her elbows? (a) Whole-body narrow-band UVB, (b) Targeted narrow-band-UVB with excimer laser, or (c) Topical psoralen plus long-wave UVA (PUVA).

– Case 2: What type of phototherapy would you use for a 50-year-old woman with extensive plaque psoriasis and type II skin who has not responded to topical therapy? She lives across the street from your office, can come for treatment in the middle of the day, and has no copay on her insurance. (a) Targeted narrow-band UVB, (b) Broad-band UVB, (c) Narrow-band UVB, (d) Retinoids plus UVB, or (e) PUVA.

Photo courtesy Dr. Lawrence F. Eichenfield.

– Case 3: How would you treat an 18-year-old man having an acute outbreak of guttate psoriasis, with explosive small plaques all over the body? (a) Narrow-band UVB with expectation for short-term treatment, (b) Narrow-band UVB with expectation of long-term maintenance, (c) PUVA, or (d) Biologic immunotherapy.

– Case 4: What’s the best phototherapy for a 59-year-old woman with palmar psoriasis that is interfering with her family business, a packing company? (a) Targeted narrow-band UVB phototherapy using an excimer laser, (b) Phototherapy using a using a hand-foot narrow-band UVB unit, (c) Oral PUVA with a hand-foot UVA unit, or (d) Topical PUVA with a hand-foot UVA unit.

Photo courtesy Dr. Gerald Krueger.

– Case 5: Which phototherapy would you choose for a 53-year-old man with extensive plaque psoriasis with big, thick plaques, including many on his back? (a) Targeted UVB with excimer laser, (b) Narrow-band UVB, (c) Retinoids plus narrow-band UVB, or (d) PUVA.

– Case 6: How would you treat a 52-year-old man with type I skin who has had plaque psoriasis for years but has become erythrodermic over the past 6 months? (a) Narrow-band UVB, (b) Retinoids plus UVB, (c) PUVA, (d) Targeted phototherapy with excimer laser, or (e) None of the above.

Answers

– Case 1: Dr. Gordon said he would choose (b) Targeted narrow-band UVB with excimer laser, although topical PUVA may be the solution sometimes, he added.

Targeted narrow-band UVB with excimer laser is "not so easy," he cautioned. On the plus side, two or three treatments per week for 6-12 weeks have a high chance of success, with more than 75% of patients achieving a Psoriasis Area and Severity Index (PASI) score of 75, or even better if you treat with higher-than-usual fluences. This method only treats involved areas and avoids treating normal skin. Perhaps more than half of patients will have long-term clearing of those limited areas at 1 year after treatment.

On the down side, severe and permanent hyperpigmentation is always a risk with the excimer laser, particularly when higher fluences are used, so it’s important to discuss this with patients when considering targeted UVB therapy. There also may be temporary blistering and pain.

"Application to extensive body surface areas is, in a scientific word, silly," Dr. Gordon said. "I bring that up because I have people in our community who are using it for people who have 20%-30% body surface area involved in psoriasis." In those cases, it’s better to refer the patient for other therapy or consider alternatives such as topical treatments or intralesional injections.

– Case 2: Broad-band UVB may be effective for this patient, though not as effective as narrow-band UVB. Retinoids plus UVB is a reasonable option in a postmenopausal 50-year-old woman. He does not use PUVA therapy "because of biases that I developed during my residency," he said.

Narrow-band UVB (c) would be Dr. Gordon’s choice, although other answers are reasonable. A clearly wrong answer is (a) Targeted narrow-band UVB, which should not be used for extensive psoriasis.

He said that he would begin treating the patient with narrow-band UVB three times per week. Some published protocols suggest starting at 400 mJ/cm2, but based on her type II skin, he said he would start at 200 mJ/m2 and increase the dose by 25-mJ increments over time. "Why 200 mJ instead of 220 mJ? The math is easier. For the people who work with me, I want the math to be really easy," he said.

Applying petrolatum or mineral oil before phototherapy can eliminate the reflectiveness of the scale to help the light penetrate, but make sure the patient is willing to do this for every treatment. "If they don’t have it as you’re building up the dose, and then they start using it, that’s when people get burned," he explained. "You just have to be consistent."

Four to 6 weeks of thrice-weekly treatments should produce a good response. There’s a dearth of data to help clinicians decide what to do after that. Some reports suggest more patients will remain clear at 1 year if treatment is decreased to twice weekly for 4 weeks and then once weekly instead of stopping phototherapy. Ultimately, this may entail fewer phototherapy sessions than stopping phototherapy and having to resume thrice-weekly sessions if the psoriasis flares again.

"Maintenance therapy is a real way to make life easier for patients with phototherapy. I think it’s a very underused process," he said. Dr. Gordon does not decrease the dose when shifting to maintenance phototherapy, but others recommend decreasing the dose by 25% during once-weekly sessions.

Data on the safety of long-term narrow-band UVB in patients with psoriasis are insufficient, but European studies suggest it does not significantly increase the incidence of nonmelanoma skin cancer. "I leave it up to the patient" to decide if this is acceptable, he said.

– Case 3: Dr. Gordon chose (a) Narrow-band UVB with expectation for short-term treatment. Unlike chronic psoriasis, guttate psoriasis is basically a self-limited disease, so short-term phototherapy is more appropriate than chronic therapy or biologics. Patients tend to respond quickly to narrow-band UVB therapy. PUVA therapy also might be a reasonable treatment, but Dr. Gordon said he has not used it for guttate psoriasis.

"Later on in life, many of these patients will come back and have plaque psoriasis," and then other treatments may be appropriate, he noted.

– Case 4: There’s no clear answer for this case because of a lack of data, according to Dr. Gordon, but he would choose (d) Topical PUVA with a hand-foot UVA unit. "The decision rests on what you sense is best for the patient," but this method is most effective in his experience, he said.

His second choice would be targeted narrow-band UVB with excimer laser, which may be effective at higher fluences but carries the risk of hyperpigmentation. The hand-foot narrow-band UVB unit also is somewhat effective. With limited disease such as this palmar psoriasis, he tries to avoid use of oral psoralen, so would not choose oral PUVA with a hand-foot UVA unit.

– Case 5: For this patient, Dr. Gordon would choose (c) Retinoids plus narrow-band UVB. Erythrodermic psoriasis features inflamed, fine-scaled skin, which is distinct from extensive plaque psoriasis. The patient’s extensive disease needs a high rate of response, so Dr. Gordon would add a retinoid to the UVB to try to boost the treatment benefit.

He advised starting acitretin first for about 1 month to make sure the patient tolerates it and to see if the disease clears on the retinoid alone, without the need for phototherapy. The protocol for UVB should account for the addition of this photosensitizing agent. Dr. Gordon usually decreases the phototherapy dose by one skin type to account for the retinoid. Others suggest decreasing the dose by 25-50 mJ/cm2.

– Case 6: No one in the audience at the meeting picked the correct answer, (d) None of the above. Phototherapy often will worsen erythrodermic psoriasis in people with light skin. Avoid phototherapy in these patients. "If you put somebody like this in a light box, you’ll be in real trouble," he warned. This patient responded well to biologic therapy.

Dr. Gordon has been a consultant for or received grants from Abbott, Amgen, Centocor, Galderma, Lilly, Pfizer, Celgene, and Merck. Also, a partner in his practice derives income from phototherapy.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS - Practical phototherapy means not thinking strictly in terms of protocols, according to Dr. Kenneth B. Gordon.

Many protocols have been published for psoriasis phototherapy, and good ones were published by the American Academy of Dermatology in early 2010 (J. Amer. Acad. Dermatol. 2010;62:114-35), said Dr. Gordon of the University of Chicago. The guidelines emphasize tailoring therapy to meet the individual patient’s needs, and physicians should consider the best treatment for each patient.

"Simple, published protocols are not sufficient if you really do phototherapy," Dr. Gordon said.

He challenged the audience members with a quiz to test their knowledge of practical phototherapy in particular cases. The cases excluded patients with psoriatic arthritis.

"There are no right answers to these questions," Dr. Gordon said. "There are some wrong answers to these questions, however."

The Quiz Cases

– Case 1: What method of phototherapy would you use to treat a young woman with limited plaque psoriasis, primarily on her elbows? (a) Whole-body narrow-band UVB, (b) Targeted narrow-band-UVB with excimer laser, or (c) Topical psoralen plus long-wave UVA (PUVA).

– Case 2: What type of phototherapy would you use for a 50-year-old woman with extensive plaque psoriasis and type II skin who has not responded to topical therapy? She lives across the street from your office, can come for treatment in the middle of the day, and has no copay on her insurance. (a) Targeted narrow-band UVB, (b) Broad-band UVB, (c) Narrow-band UVB, (d) Retinoids plus UVB, or (e) PUVA.

Photo courtesy Dr. Lawrence F. Eichenfield.

– Case 3: How would you treat an 18-year-old man having an acute outbreak of guttate psoriasis, with explosive small plaques all over the body? (a) Narrow-band UVB with expectation for short-term treatment, (b) Narrow-band UVB with expectation of long-term maintenance, (c) PUVA, or (d) Biologic immunotherapy.

– Case 4: What’s the best phototherapy for a 59-year-old woman with palmar psoriasis that is interfering with her family business, a packing company? (a) Targeted narrow-band UVB phototherapy using an excimer laser, (b) Phototherapy using a using a hand-foot narrow-band UVB unit, (c) Oral PUVA with a hand-foot UVA unit, or (d) Topical PUVA with a hand-foot UVA unit.

Photo courtesy Dr. Gerald Krueger.

– Case 5: Which phototherapy would you choose for a 53-year-old man with extensive plaque psoriasis with big, thick plaques, including many on his back? (a) Targeted UVB with excimer laser, (b) Narrow-band UVB, (c) Retinoids plus narrow-band UVB, or (d) PUVA.

– Case 6: How would you treat a 52-year-old man with type I skin who has had plaque psoriasis for years but has become erythrodermic over the past 6 months? (a) Narrow-band UVB, (b) Retinoids plus UVB, (c) PUVA, (d) Targeted phototherapy with excimer laser, or (e) None of the above.

Answers

– Case 1: Dr. Gordon said he would choose (b) Targeted narrow-band UVB with excimer laser, although topical PUVA may be the solution sometimes, he added.

Targeted narrow-band UVB with excimer laser is "not so easy," he cautioned. On the plus side, two or three treatments per week for 6-12 weeks have a high chance of success, with more than 75% of patients achieving a Psoriasis Area and Severity Index (PASI) score of 75, or even better if you treat with higher-than-usual fluences. This method only treats involved areas and avoids treating normal skin. Perhaps more than half of patients will have long-term clearing of those limited areas at 1 year after treatment.

On the down side, severe and permanent hyperpigmentation is always a risk with the excimer laser, particularly when higher fluences are used, so it’s important to discuss this with patients when considering targeted UVB therapy. There also may be temporary blistering and pain.

"Application to extensive body surface areas is, in a scientific word, silly," Dr. Gordon said. "I bring that up because I have people in our community who are using it for people who have 20%-30% body surface area involved in psoriasis." In those cases, it’s better to refer the patient for other therapy or consider alternatives such as topical treatments or intralesional injections.

– Case 2: Broad-band UVB may be effective for this patient, though not as effective as narrow-band UVB. Retinoids plus UVB is a reasonable option in a postmenopausal 50-year-old woman. He does not use PUVA therapy "because of biases that I developed during my residency," he said.

Narrow-band UVB (c) would be Dr. Gordon’s choice, although other answers are reasonable. A clearly wrong answer is (a) Targeted narrow-band UVB, which should not be used for extensive psoriasis.

He said that he would begin treating the patient with narrow-band UVB three times per week. Some published protocols suggest starting at 400 mJ/cm2, but based on her type II skin, he said he would start at 200 mJ/m2 and increase the dose by 25-mJ increments over time. "Why 200 mJ instead of 220 mJ? The math is easier. For the people who work with me, I want the math to be really easy," he said.

Applying petrolatum or mineral oil before phototherapy can eliminate the reflectiveness of the scale to help the light penetrate, but make sure the patient is willing to do this for every treatment. "If they don’t have it as you’re building up the dose, and then they start using it, that’s when people get burned," he explained. "You just have to be consistent."

Four to 6 weeks of thrice-weekly treatments should produce a good response. There’s a dearth of data to help clinicians decide what to do after that. Some reports suggest more patients will remain clear at 1 year if treatment is decreased to twice weekly for 4 weeks and then once weekly instead of stopping phototherapy. Ultimately, this may entail fewer phototherapy sessions than stopping phototherapy and having to resume thrice-weekly sessions if the psoriasis flares again.

"Maintenance therapy is a real way to make life easier for patients with phototherapy. I think it’s a very underused process," he said. Dr. Gordon does not decrease the dose when shifting to maintenance phototherapy, but others recommend decreasing the dose by 25% during once-weekly sessions.

Data on the safety of long-term narrow-band UVB in patients with psoriasis are insufficient, but European studies suggest it does not significantly increase the incidence of nonmelanoma skin cancer. "I leave it up to the patient" to decide if this is acceptable, he said.

– Case 3: Dr. Gordon chose (a) Narrow-band UVB with expectation for short-term treatment. Unlike chronic psoriasis, guttate psoriasis is basically a self-limited disease, so short-term phototherapy is more appropriate than chronic therapy or biologics. Patients tend to respond quickly to narrow-band UVB therapy. PUVA therapy also might be a reasonable treatment, but Dr. Gordon said he has not used it for guttate psoriasis.

"Later on in life, many of these patients will come back and have plaque psoriasis," and then other treatments may be appropriate, he noted.

– Case 4: There’s no clear answer for this case because of a lack of data, according to Dr. Gordon, but he would choose (d) Topical PUVA with a hand-foot UVA unit. "The decision rests on what you sense is best for the patient," but this method is most effective in his experience, he said.

His second choice would be targeted narrow-band UVB with excimer laser, which may be effective at higher fluences but carries the risk of hyperpigmentation. The hand-foot narrow-band UVB unit also is somewhat effective. With limited disease such as this palmar psoriasis, he tries to avoid use of oral psoralen, so would not choose oral PUVA with a hand-foot UVA unit.

– Case 5: For this patient, Dr. Gordon would choose (c) Retinoids plus narrow-band UVB. Erythrodermic psoriasis features inflamed, fine-scaled skin, which is distinct from extensive plaque psoriasis. The patient’s extensive disease needs a high rate of response, so Dr. Gordon would add a retinoid to the UVB to try to boost the treatment benefit.

He advised starting acitretin first for about 1 month to make sure the patient tolerates it and to see if the disease clears on the retinoid alone, without the need for phototherapy. The protocol for UVB should account for the addition of this photosensitizing agent. Dr. Gordon usually decreases the phototherapy dose by one skin type to account for the retinoid. Others suggest decreasing the dose by 25-50 mJ/cm2.

– Case 6: No one in the audience at the meeting picked the correct answer, (d) None of the above. Phototherapy often will worsen erythrodermic psoriasis in people with light skin. Avoid phototherapy in these patients. "If you put somebody like this in a light box, you’ll be in real trouble," he warned. This patient responded well to biologic therapy.

Dr. Gordon has been a consultant for or received grants from Abbott, Amgen, Centocor, Galderma, Lilly, Pfizer, Celgene, and Merck. Also, a partner in his practice derives income from phototherapy.

SDEF and this news organization are owned by Elsevier.

LAS VEGAS - Practical phototherapy means not thinking strictly in terms of protocols, according to Dr. Kenneth B. Gordon.

Many protocols have been published for psoriasis phototherapy, and good ones were published by the American Academy of Dermatology in early 2010 (J. Amer. Acad. Dermatol. 2010;62:114-35), said Dr. Gordon of the University of Chicago. The guidelines emphasize tailoring therapy to meet the individual patient’s needs, and physicians should consider the best treatment for each patient.

"Simple, published protocols are not sufficient if you really do phototherapy," Dr. Gordon said.

He challenged the audience members with a quiz to test their knowledge of practical phototherapy in particular cases. The cases excluded patients with psoriatic arthritis.

"There are no right answers to these questions," Dr. Gordon said. "There are some wrong answers to these questions, however."

The Quiz Cases

– Case 1: What method of phototherapy would you use to treat a young woman with limited plaque psoriasis, primarily on her elbows? (a) Whole-body narrow-band UVB, (b) Targeted narrow-band-UVB with excimer laser, or (c) Topical psoralen plus long-wave UVA (PUVA).

– Case 2: What type of phototherapy would you use for a 50-year-old woman with extensive plaque psoriasis and type II skin who has not responded to topical therapy? She lives across the street from your office, can come for treatment in the middle of the day, and has no copay on her insurance. (a) Targeted narrow-band UVB, (b) Broad-band UVB, (c) Narrow-band UVB, (d) Retinoids plus UVB, or (e) PUVA.

Photo courtesy Dr. Lawrence F. Eichenfield.

– Case 3: How would you treat an 18-year-old man having an acute outbreak of guttate psoriasis, with explosive small plaques all over the body? (a) Narrow-band UVB with expectation for short-term treatment, (b) Narrow-band UVB with expectation of long-term maintenance, (c) PUVA, or (d) Biologic immunotherapy.

– Case 4: What’s the best phototherapy for a 59-year-old woman with palmar psoriasis that is interfering with her family business, a packing company? (a) Targeted narrow-band UVB phototherapy using an excimer laser, (b) Phototherapy using a using a hand-foot narrow-band UVB unit, (c) Oral PUVA with a hand-foot UVA unit, or (d) Topical PUVA with a hand-foot UVA unit.

Photo courtesy Dr. Gerald Krueger.

– Case 5: Which phototherapy would you choose for a 53-year-old man with extensive plaque psoriasis with big, thick plaques, including many on his back? (a) Targeted UVB with excimer laser, (b) Narrow-band UVB, (c) Retinoids plus narrow-band UVB, or (d) PUVA.

– Case 6: How would you treat a 52-year-old man with type I skin who has had plaque psoriasis for years but has become erythrodermic over the past 6 months? (a) Narrow-band UVB, (b) Retinoids plus UVB, (c) PUVA, (d) Targeted phototherapy with excimer laser, or (e) None of the above.

Answers

– Case 1: Dr. Gordon said he would choose (b) Targeted narrow-band UVB with excimer laser, although topical PUVA may be the solution sometimes, he added.

Targeted narrow-band UVB with excimer laser is "not so easy," he cautioned. On the plus side, two or three treatments per week for 6-12 weeks have a high chance of success, with more than 75% of patients achieving a Psoriasis Area and Severity Index (PASI) score of 75, or even better if you treat with higher-than-usual fluences. This method only treats involved areas and avoids treating normal skin. Perhaps more than half of patients will have long-term clearing of those limited areas at 1 year after treatment.

On the down side, severe and permanent hyperpigmentation is always a risk with the excimer laser, particularly when higher fluences are used, so it’s important to discuss this with patients when considering targeted UVB therapy. There also may be temporary blistering and pain.

"Application to extensive body surface areas is, in a scientific word, silly," Dr. Gordon said. "I bring that up because I have people in our community who are using it for people who have 20%-30% body surface area involved in psoriasis." In those cases, it’s better to refer the patient for other therapy or consider alternatives such as topical treatments or intralesional injections.

– Case 2: Broad-band UVB may be effective for this patient, though not as effective as narrow-band UVB. Retinoids plus UVB is a reasonable option in a postmenopausal 50-year-old woman. He does not use PUVA therapy "because of biases that I developed during my residency," he said.

Narrow-band UVB (c) would be Dr. Gordon’s choice, although other answers are reasonable. A clearly wrong answer is (a) Targeted narrow-band UVB, which should not be used for extensive psoriasis.

He said that he would begin treating the patient with narrow-band UVB three times per week. Some published protocols suggest starting at 400 mJ/cm2, but based on her type II skin, he said he would start at 200 mJ/m2 and increase the dose by 25-mJ increments over time. "Why 200 mJ instead of 220 mJ? The math is easier. For the people who work with me, I want the math to be really easy," he said.

Applying petrolatum or mineral oil before phototherapy can eliminate the reflectiveness of the scale to help the light penetrate, but make sure the patient is willing to do this for every treatment. "If they don’t have it as you’re building up the dose, and then they start using it, that’s when people get burned," he explained. "You just have to be consistent."

Four to 6 weeks of thrice-weekly treatments should produce a good response. There’s a dearth of data to help clinicians decide what to do after that. Some reports suggest more patients will remain clear at 1 year if treatment is decreased to twice weekly for 4 weeks and then once weekly instead of stopping phototherapy. Ultimately, this may entail fewer phototherapy sessions than stopping phototherapy and having to resume thrice-weekly sessions if the psoriasis flares again.

"Maintenance therapy is a real way to make life easier for patients with phototherapy. I think it’s a very underused process," he said. Dr. Gordon does not decrease the dose when shifting to maintenance phototherapy, but others recommend decreasing the dose by 25% during once-weekly sessions.

Data on the safety of long-term narrow-band UVB in patients with psoriasis are insufficient, but European studies suggest it does not significantly increase the incidence of nonmelanoma skin cancer. "I leave it up to the patient" to decide if this is acceptable, he said.

– Case 3: Dr. Gordon chose (a) Narrow-band UVB with expectation for short-term treatment. Unlike chronic psoriasis, guttate psoriasis is basically a self-limited disease, so short-term phototherapy is more appropriate than chronic therapy or biologics. Patients tend to respond quickly to narrow-band UVB therapy. PUVA therapy also might be a reasonable treatment, but Dr. Gordon said he has not used it for guttate psoriasis.

"Later on in life, many of these patients will come back and have plaque psoriasis," and then other treatments may be appropriate, he noted.

– Case 4: There’s no clear answer for this case because of a lack of data, according to Dr. Gordon, but he would choose (d) Topical PUVA with a hand-foot UVA unit. "The decision rests on what you sense is best for the patient," but this method is most effective in his experience, he said.

His second choice would be targeted narrow-band UVB with excimer laser, which may be effective at higher fluences but carries the risk of hyperpigmentation. The hand-foot narrow-band UVB unit also is somewhat effective. With limited disease such as this palmar psoriasis, he tries to avoid use of oral psoralen, so would not choose oral PUVA with a hand-foot UVA unit.

– Case 5: For this patient, Dr. Gordon would choose (c) Retinoids plus narrow-band UVB. Erythrodermic psoriasis features inflamed, fine-scaled skin, which is distinct from extensive plaque psoriasis. The patient’s extensive disease needs a high rate of response, so Dr. Gordon would add a retinoid to the UVB to try to boost the treatment benefit.

He advised starting acitretin first for about 1 month to make sure the patient tolerates it and to see if the disease clears on the retinoid alone, without the need for phototherapy. The protocol for UVB should account for the addition of this photosensitizing agent. Dr. Gordon usually decreases the phototherapy dose by one skin type to account for the retinoid. Others suggest decreasing the dose by 25-50 mJ/cm2.

– Case 6: No one in the audience at the meeting picked the correct answer, (d) None of the above. Phototherapy often will worsen erythrodermic psoriasis in people with light skin. Avoid phototherapy in these patients. "If you put somebody like this in a light box, you’ll be in real trouble," he warned. This patient responded well to biologic therapy.

Dr. Gordon has been a consultant for or received grants from Abbott, Amgen, Centocor, Galderma, Lilly, Pfizer, Celgene, and Merck. Also, a partner in his practice derives income from phototherapy.

SDEF and this news organization are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

"Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition," the draft report stated. AHRQ uploaded the draft report Dec. 21 to the Effective Care portion of its Web site. Comments on the report are due by Jan. 19. http://www.effectivehealthcare.ahrq.gov/index.cfm/research-available-for-comment/comment-draft-reports/?pageaction=displaydraftcommentform&topicid=203&productid=598&documenttype=draftReport  The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer’s Enbrel. http://www.skinandallergynews.com/index.php?id=372&cHash=071010&tx_ttnews[tt_news]=17519

The draft report noted that about 520,000 adults in the U.S. have psoriatic arthritis, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi and Remicade are approved by FDA to be used in patients with PsA.

Key Questions

The comparative effectiveness study aimed to answer four key questions:

For patients with PsA, do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

For patients with PsA, do drug therapies differ in their ability to improve patient reported symptoms, functional capacity or quality of life?

For patients with PsA, do drug therapies differ in harms, tolerability, adherence or adverse effects?

What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

No Clinical Consensus

The draft report noted that experts "have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare – e.g. oral DMARDs with corticosteroids, oral DMARDs with biologic DMARDs, triple combination of corticosteroids, oral DMARDs and biologic DMARDs. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent."

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

Contributing to the issue is the lack of trial evidence. "In patients with PsA, historically, few trials have been conducted with only minimal research before biologic agents were introduced; management options tended to be adopted from rheumatoid arthritis (RA) trial evidence," the draft report stated.

Starting from a base of 3,487 citations, researchers included 19 published articles reporting on 12 studies, including no head-to-head randomized controlled trials, no head-to-head nonrandomized controlled trials, 9 placebo-controlled trials, 2 meta-analyses or systematic reviews, and 1 observational study.

Report authors called for more comparative research to be done "to help clinicians and researchers arrive at stronger conclusions on the comparative efficacy, effectiveness, quality of life, and harms of medications for PsA," with a specific call for head-to-head randomized controlled trials to build the knowledge base.

Gregory Twachtman is a writer for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

"Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition," the draft report stated. AHRQ uploaded the draft report Dec. 21 to the Effective Care portion of its Web site. Comments on the report are due by Jan. 19. http://www.effectivehealthcare.ahrq.gov/index.cfm/research-available-for-comment/comment-draft-reports/?pageaction=displaydraftcommentform&topicid=203&productid=598&documenttype=draftReport  The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer’s Enbrel. http://www.skinandallergynews.com/index.php?id=372&cHash=071010&tx_ttnews[tt_news]=17519

The draft report noted that about 520,000 adults in the U.S. have psoriatic arthritis, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi and Remicade are approved by FDA to be used in patients with PsA.

Key Questions

The comparative effectiveness study aimed to answer four key questions:

For patients with PsA, do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

For patients with PsA, do drug therapies differ in their ability to improve patient reported symptoms, functional capacity or quality of life?

For patients with PsA, do drug therapies differ in harms, tolerability, adherence or adverse effects?

What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

No Clinical Consensus

The draft report noted that experts "have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare – e.g. oral DMARDs with corticosteroids, oral DMARDs with biologic DMARDs, triple combination of corticosteroids, oral DMARDs and biologic DMARDs. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent."

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

Contributing to the issue is the lack of trial evidence. "In patients with PsA, historically, few trials have been conducted with only minimal research before biologic agents were introduced; management options tended to be adopted from rheumatoid arthritis (RA) trial evidence," the draft report stated.

Starting from a base of 3,487 citations, researchers included 19 published articles reporting on 12 studies, including no head-to-head randomized controlled trials, no head-to-head nonrandomized controlled trials, 9 placebo-controlled trials, 2 meta-analyses or systematic reviews, and 1 observational study.

Report authors called for more comparative research to be done "to help clinicians and researchers arrive at stronger conclusions on the comparative efficacy, effectiveness, quality of life, and harms of medications for PsA," with a specific call for head-to-head randomized controlled trials to build the knowledge base.

Gregory Twachtman is a writer for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

A comparative effectiveness study on drug therapies used to treat psoriatic arthritis in adults determined that evidence is insufficient to draw any conclusions.

"Overall, the data are quite limited and the evidence is insufficient to draw firm conclusions on comparative efficacy, effectiveness, and harms of either oral or biologic DMARDs [disease-modifying antirheumatic drugs] in this condition," the draft report stated. AHRQ uploaded the draft report Dec. 21 to the Effective Care portion of its Web site. Comments on the report are due by Jan. 19. http://www.effectivehealthcare.ahrq.gov/index.cfm/research-available-for-comment/comment-draft-reports/?pageaction=displaydraftcommentform&topicid=203&productid=598&documenttype=draftReport  The draft did not identify the lead investigators of the study.

AHRQ's findings come soon after the U.K.'s National Institute for Clinical Excellence rejected Simponi for the treatment of active and progressive psoriatic arthritis in adults, claiming that evidence revealed that the Schering Plough/Johnson & Johnson product was not as effective as Pfizer’s Enbrel. http://www.skinandallergynews.com/index.php?id=372&cHash=071010&tx_ttnews[tt_news]=17519

The draft report noted that about 520,000 adults in the U.S. have psoriatic arthritis, with treatments aimed primarily at controlling pain and inflammation and, ultimately, at slowing or arresting the progression of joint destruction.

The study compared a variety of oral and biologic DMARDs, including Simponi (golimumab) and Enbrel (etanercept), as well as Sanofi-Synthelabo's Plaquenil (hydroxychloroquine), Sanofi-Aventis' Arava (leflunomide), methotrexate, sulfasalazine, Abbott's Humira (adalimumab), UCB's Cimzia (certolizumab) and J&J's Remicade (infliximab). Humira, Enbrel, Simponi and Remicade are approved by FDA to be used in patients with PsA.

Key Questions

The comparative effectiveness study aimed to answer four key questions:

For patients with PsA, do drug therapies differ in their ability to reduce disease activity, to slow or limit progression of radiographic joint damage, or to maintain remission?

For patients with PsA, do drug therapies differ in their ability to improve patient reported symptoms, functional capacity or quality of life?

For patients with PsA, do drug therapies differ in harms, tolerability, adherence or adverse effects?

What are the comparative benefits and harms of drug therapies for PsA in subgroups of patients based on stage of disease, history of prior therapy, demographics, concomitant therapies or comorbidities?

The limited evidence that surfaced during research addressed the first three questions but nothing could be found on the fourth.

No Clinical Consensus

The draft report noted that experts "have not arrived at consensus about the comparative effectiveness of corticosteroids, oral DMARDs, and biologic DMARDs for treating PsA. More importantly, it is unclear how the effectiveness and safety of different types of combination therapy compare – e.g. oral DMARDs with corticosteroids, oral DMARDs with biologic DMARDs, triple combination of corticosteroids, oral DMARDs and biologic DMARDs. In addition, there is debate about how early in the disease process combination therapy should be initiated and whether patients will respond to a biologic agent if they have previously failed a different biologic agent."

The draft report added that questions remain about the risks of these agents. There is also limited understanding of the benefits and risks regarding subpopulations, including ethnic minorities, the elderly, pregnant women, and patients with other comorbidities.

Contributing to the issue is the lack of trial evidence. "In patients with PsA, historically, few trials have been conducted with only minimal research before biologic agents were introduced; management options tended to be adopted from rheumatoid arthritis (RA) trial evidence," the draft report stated.

Starting from a base of 3,487 citations, researchers included 19 published articles reporting on 12 studies, including no head-to-head randomized controlled trials, no head-to-head nonrandomized controlled trials, 9 placebo-controlled trials, 2 meta-analyses or systematic reviews, and 1 observational study.

Report authors called for more comparative research to be done "to help clinicians and researchers arrive at stronger conclusions on the comparative efficacy, effectiveness, quality of life, and harms of medications for PsA," with a specific call for head-to-head randomized controlled trials to build the knowledge base.

Gregory Twachtman is a writer for "The Pink Sheet." This news organization and "The Pink Sheet" are owned by Elsevier.

GOTHENBURG, SWEDEN – For psoriasis patients, all tumor necrosis factor inhibitors are associated with roughly the same risks for serious infection, according to a meta-analysis of data from major randomized clinical trials and their long-term, open-label extensions.

Regardless of whether etanercept, infliximab, or adalimumab was the prescribed agent, the serious infection risk for psoriasis patients was in the range of 1.0-1.5 cases per 100 patient-years of therapy. Thus, 1 in every 10 patients on any given TNF-inhibitor could expect to have about one serious skin infection every 10 years, Dr. Richard Langley said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology.

"Serious" infections in this context may or may not be a big deal. A serious infection, under the definition employed in the clinical trials, is one requiring intravenous antibiotics or hospitalization. The number-needed-to-harm – that is, the number of psoriasis patients who would need to be treated with an anti-TNF biologic rather than placebo for 1 year in order to cause one additional serious infection – is at least two orders of magnitude larger than the number-needed-to-treat in order to achieve a PASI 75 treatment response. That’s an extremely favorable risk-benefit ratio, said Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, Nova Scotia.

His recently published meta-analysis (Br. J. Dermatol. 2010 Apr 14 [Epub ahead of print]) showed that the number-needed-to-treat was 1.4 patients with infliximab dosed at 5 mg/kg, 1.6 for adalimumab at 40 mg every 2 weeks, 2.3 for etanercept at 50 mg twice weekly, and 3.2 for etanercept at 50 mg once weekly or 25 mg twice weekly, he reported at the satellite symposium sponsored by Abbott.

Serious infections warrant a temporary interruption of anti-TNF therapy. But so do clinically important infections that don’t rise to the threshold of "serious," he said, for example, a case of cellulitis being treated on an outpatient basis with oral antibiotics. Continuing anti-TNF therapy in such a patient increases the risk of a more complicated infection.

"I would submit to you that it’s better to be conservative in situations like this and withhold therapy," he said.

All of the TNF inhibitors – indeed, probably all biologic therapies – increase the risk of upper respiratory infections, bronchitis, and nasopharyngitis. These are minor infections, and it’s generally appropriate to push ahead with therapy, as was routine practice in the clinical trials, Dr. Langley noted.

However, participants in clinical trials are a carefully selected subgroup. They often are quite dissimilar in key ways to patients encountered in daily clinical practice. Registry data better reflect real-world patients. And while registries of psoriasis patients on biologic therapies are now up and running, the follow-up isn’t yet sufficiently long for data analysis.

Dermatologists seeking to gain a fuller understanding of the safety issues surrounding the TNF antagonists can turn to the rheumatology experience with biologics. British Society for Rheumatology Biologics Registry data show an incidence of skin and soft tissue infections in rheumatoid arthritis patients that is 3.0 cases per 1,000 patient-years of treatment with methotrexate or other traditional disease-modifying anti-rheumatic drugs (DMARDs) and 12.0 per 1,000 patient-years in those on TNF inhibitors, for an adjusted 4.3-fold increased relative risk accompanying the newer agents (Arthritis Rheum. 2006 54:2,368-76).

But it’s important to remember that psoriasis patients differ in important ways from those with rheumatoid arthritis, Dr. Langley noted. The arthritis patients are much more likely, for example, to be on concomitant treatment with systemic corticosteroids, and perhaps to have intrinsic disease-related qualities predisposing to serious infections.

This point was effectively underscored in a formal analysis of serious adverse events in clinical trials of adalimumab across all indications (Ann. Rheum. Dis. 2009;68:1,863-9). The incidence of serious infections per 100 patient-years of exposure to adalimumab was 4.7 for rheumatoid arthritis patients, compared with 1.3 in those being treated for psoriasis.

Dr. Langley disclosed serving as a speaker for Abbott and having financial relationships with numerous other pharmaceutical companies that manufacture psoriasis therapies.

GOTHENBURG, SWEDEN – For psoriasis patients, all tumor necrosis factor inhibitors are associated with roughly the same risks for serious infection, according to a meta-analysis of data from major randomized clinical trials and their long-term, open-label extensions.

Regardless of whether etanercept, infliximab, or adalimumab was the prescribed agent, the serious infection risk for psoriasis patients was in the range of 1.0-1.5 cases per 100 patient-years of therapy. Thus, 1 in every 10 patients on any given TNF-inhibitor could expect to have about one serious skin infection every 10 years, Dr. Richard Langley said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology.

"Serious" infections in this context may or may not be a big deal. A serious infection, under the definition employed in the clinical trials, is one requiring intravenous antibiotics or hospitalization. The number-needed-to-harm – that is, the number of psoriasis patients who would need to be treated with an anti-TNF biologic rather than placebo for 1 year in order to cause one additional serious infection – is at least two orders of magnitude larger than the number-needed-to-treat in order to achieve a PASI 75 treatment response. That’s an extremely favorable risk-benefit ratio, said Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, Nova Scotia.

His recently published meta-analysis (Br. J. Dermatol. 2010 Apr 14 [Epub ahead of print]) showed that the number-needed-to-treat was 1.4 patients with infliximab dosed at 5 mg/kg, 1.6 for adalimumab at 40 mg every 2 weeks, 2.3 for etanercept at 50 mg twice weekly, and 3.2 for etanercept at 50 mg once weekly or 25 mg twice weekly, he reported at the satellite symposium sponsored by Abbott.

Serious infections warrant a temporary interruption of anti-TNF therapy. But so do clinically important infections that don’t rise to the threshold of "serious," he said, for example, a case of cellulitis being treated on an outpatient basis with oral antibiotics. Continuing anti-TNF therapy in such a patient increases the risk of a more complicated infection.

"I would submit to you that it’s better to be conservative in situations like this and withhold therapy," he said.

All of the TNF inhibitors – indeed, probably all biologic therapies – increase the risk of upper respiratory infections, bronchitis, and nasopharyngitis. These are minor infections, and it’s generally appropriate to push ahead with therapy, as was routine practice in the clinical trials, Dr. Langley noted.

However, participants in clinical trials are a carefully selected subgroup. They often are quite dissimilar in key ways to patients encountered in daily clinical practice. Registry data better reflect real-world patients. And while registries of psoriasis patients on biologic therapies are now up and running, the follow-up isn’t yet sufficiently long for data analysis.

Dermatologists seeking to gain a fuller understanding of the safety issues surrounding the TNF antagonists can turn to the rheumatology experience with biologics. British Society for Rheumatology Biologics Registry data show an incidence of skin and soft tissue infections in rheumatoid arthritis patients that is 3.0 cases per 1,000 patient-years of treatment with methotrexate or other traditional disease-modifying anti-rheumatic drugs (DMARDs) and 12.0 per 1,000 patient-years in those on TNF inhibitors, for an adjusted 4.3-fold increased relative risk accompanying the newer agents (Arthritis Rheum. 2006 54:2,368-76).

But it’s important to remember that psoriasis patients differ in important ways from those with rheumatoid arthritis, Dr. Langley noted. The arthritis patients are much more likely, for example, to be on concomitant treatment with systemic corticosteroids, and perhaps to have intrinsic disease-related qualities predisposing to serious infections.

This point was effectively underscored in a formal analysis of serious adverse events in clinical trials of adalimumab across all indications (Ann. Rheum. Dis. 2009;68:1,863-9). The incidence of serious infections per 100 patient-years of exposure to adalimumab was 4.7 for rheumatoid arthritis patients, compared with 1.3 in those being treated for psoriasis.

Dr. Langley disclosed serving as a speaker for Abbott and having financial relationships with numerous other pharmaceutical companies that manufacture psoriasis therapies.

GOTHENBURG, SWEDEN – For psoriasis patients, all tumor necrosis factor inhibitors are associated with roughly the same risks for serious infection, according to a meta-analysis of data from major randomized clinical trials and their long-term, open-label extensions.

Regardless of whether etanercept, infliximab, or adalimumab was the prescribed agent, the serious infection risk for psoriasis patients was in the range of 1.0-1.5 cases per 100 patient-years of therapy. Thus, 1 in every 10 patients on any given TNF-inhibitor could expect to have about one serious skin infection every 10 years, Dr. Richard Langley said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology.

"Serious" infections in this context may or may not be a big deal. A serious infection, under the definition employed in the clinical trials, is one requiring intravenous antibiotics or hospitalization. The number-needed-to-harm – that is, the number of psoriasis patients who would need to be treated with an anti-TNF biologic rather than placebo for 1 year in order to cause one additional serious infection – is at least two orders of magnitude larger than the number-needed-to-treat in order to achieve a PASI 75 treatment response. That’s an extremely favorable risk-benefit ratio, said Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, Nova Scotia.

His recently published meta-analysis (Br. J. Dermatol. 2010 Apr 14 [Epub ahead of print]) showed that the number-needed-to-treat was 1.4 patients with infliximab dosed at 5 mg/kg, 1.6 for adalimumab at 40 mg every 2 weeks, 2.3 for etanercept at 50 mg twice weekly, and 3.2 for etanercept at 50 mg once weekly or 25 mg twice weekly, he reported at the satellite symposium sponsored by Abbott.

Serious infections warrant a temporary interruption of anti-TNF therapy. But so do clinically important infections that don’t rise to the threshold of "serious," he said, for example, a case of cellulitis being treated on an outpatient basis with oral antibiotics. Continuing anti-TNF therapy in such a patient increases the risk of a more complicated infection.

"I would submit to you that it’s better to be conservative in situations like this and withhold therapy," he said.

All of the TNF inhibitors – indeed, probably all biologic therapies – increase the risk of upper respiratory infections, bronchitis, and nasopharyngitis. These are minor infections, and it’s generally appropriate to push ahead with therapy, as was routine practice in the clinical trials, Dr. Langley noted.

However, participants in clinical trials are a carefully selected subgroup. They often are quite dissimilar in key ways to patients encountered in daily clinical practice. Registry data better reflect real-world patients. And while registries of psoriasis patients on biologic therapies are now up and running, the follow-up isn’t yet sufficiently long for data analysis.

Dermatologists seeking to gain a fuller understanding of the safety issues surrounding the TNF antagonists can turn to the rheumatology experience with biologics. British Society for Rheumatology Biologics Registry data show an incidence of skin and soft tissue infections in rheumatoid arthritis patients that is 3.0 cases per 1,000 patient-years of treatment with methotrexate or other traditional disease-modifying anti-rheumatic drugs (DMARDs) and 12.0 per 1,000 patient-years in those on TNF inhibitors, for an adjusted 4.3-fold increased relative risk accompanying the newer agents (Arthritis Rheum. 2006 54:2,368-76).

But it’s important to remember that psoriasis patients differ in important ways from those with rheumatoid arthritis, Dr. Langley noted. The arthritis patients are much more likely, for example, to be on concomitant treatment with systemic corticosteroids, and perhaps to have intrinsic disease-related qualities predisposing to serious infections.

This point was effectively underscored in a formal analysis of serious adverse events in clinical trials of adalimumab across all indications (Ann. Rheum. Dis. 2009;68:1,863-9). The incidence of serious infections per 100 patient-years of exposure to adalimumab was 4.7 for rheumatoid arthritis patients, compared with 1.3 in those being treated for psoriasis.

Dr. Langley disclosed serving as a speaker for Abbott and having financial relationships with numerous other pharmaceutical companies that manufacture psoriasis therapies.

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study presented at the annual congress of the European Academy for Dermatology and Venereology.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study presented at the annual congress of the European Academy for Dermatology and Venereology.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.

GOTHENBURG, SWEDEN - Compliance with topical dermatologic therapies is worse than most physicians realize, according to a new study presented at the annual congress of the European Academy for Dermatology and Venereology.

Through a series of Danish studies utilizing the nation’s comprehensive electronic medical and pharmacy records system, investigators concluded that more than one in three new prescriptions for creams and ointments for dermatologic diseases is never picked up. And for those who actually do fill their prescriptions, treatment adherence just goes downhill from there.

"I would say that even an optimistic estimate would be that only one in five patients truly follows the treatment advice and takes their treatment at home. It's really an alarming figure. The typical result is that the patient comes in complaining, 'It didn't work, doctor,' and now they expect another prescription," Dr. Jørgen Serup said.

"Creams and ointments are truly messy, greasy, cumbersome, and patients can only treat a limited number of lesions on a limited area, and only on certain anatomic sites. These are serious limitations. This is a lot more difficult than just taking a pill," added Dr. Serup, professor of dermatology at Copenhagen University. "Maybe the creams and ointments are really obsolete because they are so difficult to use in clinical practice. Maybe we should be using much more systemic therapy."

He and his colleagues examined all new prescriptions for previously untried medications issued for dermatologic outpatients at Copenhagen University Hospital every 15th day during 2006. Thirty-one percent of the 322 eligible patients exhibited what Dr. Serup termed "primary nonadherence," meaning they never collected their medication. Patients with psoriasis were the biggest offenders; they failed to pick up their medications 44% of the time. This was also the case for 31% of atopic dermatitis patients, 12% being treated for skin infections, and 9% of acne patients.

Thirty-five percent of prescriptions for topical preparations remained behind the pharmacy counter. Prescriptions for systemic agents fared much better; only 14% went unredeemed (J. Am. Acad. Dermatol. 2008;59:27-33).

In another study, the Danish dermatologists visited the homes of 17 first-time dermatologic outpatients who had been given prescriptions for previously untried topical medications. Upon weighing the patients' drug containers, the investigators found only 1 of the 17 patients used the directed dosage. Two patients never picked up their prescriptions, 13 used too little drug, and 1 patient used too much (J. Am. Acad. Dermatol. 2008;59:975-80).

Inadequate application of topical agents is another problem. In a joint study conducted with Swedish dermatologists, the Danish investigators found that highly motivated volunteers applied a fluorescent test cream to only 69% of the skin surface as directed. Areas prone to neglect included the upper breast, axilla and surrounding skin, posterior trunk, legs, and soles of the feet (Br. J. Dermatol. 2007;156:974-8).

Yet another form of treatment noncompliance results from patients’ failure to show up for scheduled appointments. Dr. Serup and coworkers recently reviewed 3,592 patient appointments at the university hospital’s outpatient dermatology clinic and found that 13% of patients didn’t keep their appointments. Patients failed to show for about 10% of all appointments because of forgetfulness or a variety of excuses; this was most common in patients under age 30. The rest of the no-shows were caused by booking mistakes by the clinic staff.

Poor physician-patient communication plays a role in noncompliance as well, as underscored in a study in which Dr. Serup’s colleagues taped and studied 57 dermatologic consultations with 17 dermatology patients, all of whom received new prescriptions for topical agents. At follow-up 2 weeks later, only 41% of patients were familiar with their diagnosis, 71% understood the recommended number of treatment applications per day, and 35% knew the planned duration of treatment. Just 12% of patients understood the proper quantity of the topical agent to be applied; their ignorance on this score was understandable, since dermatologists covered that key issue in only 18% of the recorded clinic visits. Moreover, dermatologists provided a clear explanation of the diagnosis in only 65% of cases (J. Dermatolog. Treat. 2009;20:190-3).

On a more optimistic note, Dr. Serup believes mobile phones and other modern tools can be better utilized to boost compliance among dermatology patients, especially the younger ones, who tend to have the lowest compliance rates. The literature shows that text message reminders and email consultations are effective in this regard, at least within general medicine. A system recently developed in Sweden allows patients to install software on their mobile phone so they can monitor their disease and phone their physician for data transfer and to communicate about therapy. Dr. Serup has utilized this technology to follow the course of treatment in patients with atopic dermatitis.

"It is exactly the language of the [younger generation] to have the information displayed on a mobile phone screen. This can't be used in the elderly, though," he said.

He declared having no relevant financial interests.