Psoriasis

BUENOS AIRES – Despite some early letdowns in clinical trials, biologic therapies targeting nearly every point in the pathway of the known pathogenesis of systemic lupus erythematosus are currently in the pipeline.

At the International Congress on Systemic Lupus Erythematosus, investigators presented promising new data on several experimental biologics. And in the shadow of some costly failures, they also discussed ways to refine endpoints, inclusion criteria, and the use of background medicines to make trial results for these agents clearer.

Biomarker-driven response to rontalizumab

Rontalizumab, a humanized antibody against anti-interferon-alpha, was shown in a phase II randomized controlled trial of 159 patients with moderate to severe SLE to improve signs and symptoms, flare rates, and need for steroids at 24 weeks in the subset of patients who had low interferon signature gene expression metric (ISM), an emerging biomarker in SLE, at baseline.

Although whether patients are classified as ISM high or low makes little difference in terms of measurable disease activity, it does appear to affect how treatments work. "No matter what drug you look at, the impact differs depending on whether the patients are ISM high or low," said Dr. Joan T. Merrill, one of the coauthors of the rontalizumab study, which was presented at the meeting by Dr. William Kennedy, senior medical director of Genentech.

Rontalizumab was associated with improvement in the ISM-low subgroup in the trial, which compared both intravenous and subcutaneous forms of rontalizumab with placebo. In ISM-low patients, a quarter of the total enrolled, IV rontalizumab vs. placebo SLE Responder Index (SRI) response rates were 75% vs. 18%. Treatment groups saw a nearly 40% reduced risk of disease flare based on SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index) flare rates, compared with placebo (hazard ratio 0.61 [90% confidence interval 0.46-0.81; P = .0040]), driven by ISM-low patients. Also, 91% of ISM-low patients in the treatment groups achieved prednisone reduction (10 mg/day) by week 24, compared with 67% of placebo subjects (Lupus 2013;22[Suppl.]:O22).

Limiting background medications in trials

Background immunosuppressants were not used in the rontalizumab study, and steroids were limited. Dr. Merrill, of the University of Oklahoma Health Sciences Center, Oklahoma City, discussed some of the thinking behind this. Limiting background medications "can lead to more interpretable results," she said. While many investigators have argued that only the sickest and most refractory patients should be enrolled in SLE clinical trials as a way to discern a clearer differences between treatment and placebo, Dr. Merrill instead championed recruiting less-sick patients for whom it is safer to withdraw or minimize background medicines.

Patients without severe disease will still die early and accumulate increasing damage over time, Dr. Merrill said. "They represent a huge unmet need. So if we could do trials with these patients and limit the background noise caused by their medications, perhaps we could also see a difference between treatment and placebo. Trials would be easier to recruit, we would see fewer infections, and most importantly, there would be a bigger market for pharma companies to pursue."

Targeting CD22 antigen on B cells

Two randomized, placebo-controlled trials of epratuzumab, a monoclonal antibody targeting CD22 antigen on B cells, had to be terminated when drug supply was interrupted. However, the early findings had shown clinically meaningful improvements in disease activity and corticosteroid sparing. Final results from an open-label extension study for SLE patients previously enrolled in these trials (n = 429), sponsored by UCB Pharma, showed that continued administration of epratuzumab resulted in sustained improvements after a mean four years of treatment, with no new safety signals (Lupus 2013;22[Suppl.]:O25).

Phase II data on blisibimod

Blisibimod, a biologic injected subcutaneously that inhibits B-cell activating factor, or BAFF, was investigated in a phase IIb manufacturer-sponsored trial of 547 patients with anti-dsDNA or anti-nuclear antibodies and SELENA-SLEDAI score of 6 or higher at baseline. Dr. Morton Scheinberg of Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil, led the trial, sponsored by Anthera Pharmaceuticals, in which patients were randomized to one of three doses or placebo. The composite primary endpoint, SRI-5 (defined as a 5-point improvement in SELENA-SLEDAI, no new BILAG A or 2B organ domain scores, and no worsening in Physician’s Global Assessment) was not met because efficacy was not shown in the lower doses. However, more subjects who received the highest dose (200 mg once weekly) met the response criteria starting in week 16 (8%, P = .14), through week 24 (8.2%, P = .15), reaching statistical significance at week 20 (Lupus 2013;22[Suppl.]:O21).

Improving on past trial missteps

One of the coinvestigators on the blisibimod trial, Dr. Richard A. Furie, discussed missteps in the design of earlier studies. "Trials of new biologic therapies have taught us to be humble and logical, and to persevere – we’ve made a lot of mistakes over last 20 years," he told the conference, pointing to a handful of trials in which subjects did not have serologic evidence of disease at baseline. "In my book, if someone is clinically active they should have autoantibodies," he said. "So the rules for entry were changed for all trials."

Dr. Furie, chief of the division of rheumatology and allergy-clinical immunology in the North Shore–LIJ Health System and professor of medicine at Hofstra University, Hempstead, N.Y., said that while inclusion criteria had improved, investigators of biologic agents still had far to go in refining SLE trial endpoints. "No two endpoints are the same – we’ve customized the endpoints and are struggling with extrarenal trials whether it should be a single or composite endpoint, whether it should be based on SLEDAI or BILAG alone or should we use SRI – there is no consensus." Echoing Dr. Merrill, he stressed that background medications were another area in need of increased scrutiny and consensus. "Each trial has handled steroids and immunosuppressants differently," he said.

Dr. Merrill has received support from Genentech. Dr. Furie has received support from Anthera, Genentech, and UCB Pharma. Both rheumatologists have received support from many other companies involved in lupus research and therapy.

BUENOS AIRES – Despite some early letdowns in clinical trials, biologic therapies targeting nearly every point in the pathway of the known pathogenesis of systemic lupus erythematosus are currently in the pipeline.

At the International Congress on Systemic Lupus Erythematosus, investigators presented promising new data on several experimental biologics. And in the shadow of some costly failures, they also discussed ways to refine endpoints, inclusion criteria, and the use of background medicines to make trial results for these agents clearer.

Biomarker-driven response to rontalizumab

Rontalizumab, a humanized antibody against anti-interferon-alpha, was shown in a phase II randomized controlled trial of 159 patients with moderate to severe SLE to improve signs and symptoms, flare rates, and need for steroids at 24 weeks in the subset of patients who had low interferon signature gene expression metric (ISM), an emerging biomarker in SLE, at baseline.

Although whether patients are classified as ISM high or low makes little difference in terms of measurable disease activity, it does appear to affect how treatments work. "No matter what drug you look at, the impact differs depending on whether the patients are ISM high or low," said Dr. Joan T. Merrill, one of the coauthors of the rontalizumab study, which was presented at the meeting by Dr. William Kennedy, senior medical director of Genentech.

Rontalizumab was associated with improvement in the ISM-low subgroup in the trial, which compared both intravenous and subcutaneous forms of rontalizumab with placebo. In ISM-low patients, a quarter of the total enrolled, IV rontalizumab vs. placebo SLE Responder Index (SRI) response rates were 75% vs. 18%. Treatment groups saw a nearly 40% reduced risk of disease flare based on SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index) flare rates, compared with placebo (hazard ratio 0.61 [90% confidence interval 0.46-0.81; P = .0040]), driven by ISM-low patients. Also, 91% of ISM-low patients in the treatment groups achieved prednisone reduction (10 mg/day) by week 24, compared with 67% of placebo subjects (Lupus 2013;22[Suppl.]:O22).

Limiting background medications in trials

Background immunosuppressants were not used in the rontalizumab study, and steroids were limited. Dr. Merrill, of the University of Oklahoma Health Sciences Center, Oklahoma City, discussed some of the thinking behind this. Limiting background medications "can lead to more interpretable results," she said. While many investigators have argued that only the sickest and most refractory patients should be enrolled in SLE clinical trials as a way to discern a clearer differences between treatment and placebo, Dr. Merrill instead championed recruiting less-sick patients for whom it is safer to withdraw or minimize background medicines.

Patients without severe disease will still die early and accumulate increasing damage over time, Dr. Merrill said. "They represent a huge unmet need. So if we could do trials with these patients and limit the background noise caused by their medications, perhaps we could also see a difference between treatment and placebo. Trials would be easier to recruit, we would see fewer infections, and most importantly, there would be a bigger market for pharma companies to pursue."

Targeting CD22 antigen on B cells

Two randomized, placebo-controlled trials of epratuzumab, a monoclonal antibody targeting CD22 antigen on B cells, had to be terminated when drug supply was interrupted. However, the early findings had shown clinically meaningful improvements in disease activity and corticosteroid sparing. Final results from an open-label extension study for SLE patients previously enrolled in these trials (n = 429), sponsored by UCB Pharma, showed that continued administration of epratuzumab resulted in sustained improvements after a mean four years of treatment, with no new safety signals (Lupus 2013;22[Suppl.]:O25).

Phase II data on blisibimod

Blisibimod, a biologic injected subcutaneously that inhibits B-cell activating factor, or BAFF, was investigated in a phase IIb manufacturer-sponsored trial of 547 patients with anti-dsDNA or anti-nuclear antibodies and SELENA-SLEDAI score of 6 or higher at baseline. Dr. Morton Scheinberg of Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil, led the trial, sponsored by Anthera Pharmaceuticals, in which patients were randomized to one of three doses or placebo. The composite primary endpoint, SRI-5 (defined as a 5-point improvement in SELENA-SLEDAI, no new BILAG A or 2B organ domain scores, and no worsening in Physician’s Global Assessment) was not met because efficacy was not shown in the lower doses. However, more subjects who received the highest dose (200 mg once weekly) met the response criteria starting in week 16 (8%, P = .14), through week 24 (8.2%, P = .15), reaching statistical significance at week 20 (Lupus 2013;22[Suppl.]:O21).

Improving on past trial missteps

One of the coinvestigators on the blisibimod trial, Dr. Richard A. Furie, discussed missteps in the design of earlier studies. "Trials of new biologic therapies have taught us to be humble and logical, and to persevere – we’ve made a lot of mistakes over last 20 years," he told the conference, pointing to a handful of trials in which subjects did not have serologic evidence of disease at baseline. "In my book, if someone is clinically active they should have autoantibodies," he said. "So the rules for entry were changed for all trials."

Dr. Furie, chief of the division of rheumatology and allergy-clinical immunology in the North Shore–LIJ Health System and professor of medicine at Hofstra University, Hempstead, N.Y., said that while inclusion criteria had improved, investigators of biologic agents still had far to go in refining SLE trial endpoints. "No two endpoints are the same – we’ve customized the endpoints and are struggling with extrarenal trials whether it should be a single or composite endpoint, whether it should be based on SLEDAI or BILAG alone or should we use SRI – there is no consensus." Echoing Dr. Merrill, he stressed that background medications were another area in need of increased scrutiny and consensus. "Each trial has handled steroids and immunosuppressants differently," he said.

Dr. Merrill has received support from Genentech. Dr. Furie has received support from Anthera, Genentech, and UCB Pharma. Both rheumatologists have received support from many other companies involved in lupus research and therapy.

BUENOS AIRES – Despite some early letdowns in clinical trials, biologic therapies targeting nearly every point in the pathway of the known pathogenesis of systemic lupus erythematosus are currently in the pipeline.

At the International Congress on Systemic Lupus Erythematosus, investigators presented promising new data on several experimental biologics. And in the shadow of some costly failures, they also discussed ways to refine endpoints, inclusion criteria, and the use of background medicines to make trial results for these agents clearer.

Biomarker-driven response to rontalizumab

Rontalizumab, a humanized antibody against anti-interferon-alpha, was shown in a phase II randomized controlled trial of 159 patients with moderate to severe SLE to improve signs and symptoms, flare rates, and need for steroids at 24 weeks in the subset of patients who had low interferon signature gene expression metric (ISM), an emerging biomarker in SLE, at baseline.

Although whether patients are classified as ISM high or low makes little difference in terms of measurable disease activity, it does appear to affect how treatments work. "No matter what drug you look at, the impact differs depending on whether the patients are ISM high or low," said Dr. Joan T. Merrill, one of the coauthors of the rontalizumab study, which was presented at the meeting by Dr. William Kennedy, senior medical director of Genentech.

Rontalizumab was associated with improvement in the ISM-low subgroup in the trial, which compared both intravenous and subcutaneous forms of rontalizumab with placebo. In ISM-low patients, a quarter of the total enrolled, IV rontalizumab vs. placebo SLE Responder Index (SRI) response rates were 75% vs. 18%. Treatment groups saw a nearly 40% reduced risk of disease flare based on SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index) flare rates, compared with placebo (hazard ratio 0.61 [90% confidence interval 0.46-0.81; P = .0040]), driven by ISM-low patients. Also, 91% of ISM-low patients in the treatment groups achieved prednisone reduction (10 mg/day) by week 24, compared with 67% of placebo subjects (Lupus 2013;22[Suppl.]:O22).

Limiting background medications in trials

Background immunosuppressants were not used in the rontalizumab study, and steroids were limited. Dr. Merrill, of the University of Oklahoma Health Sciences Center, Oklahoma City, discussed some of the thinking behind this. Limiting background medications "can lead to more interpretable results," she said. While many investigators have argued that only the sickest and most refractory patients should be enrolled in SLE clinical trials as a way to discern a clearer differences between treatment and placebo, Dr. Merrill instead championed recruiting less-sick patients for whom it is safer to withdraw or minimize background medicines.

Patients without severe disease will still die early and accumulate increasing damage over time, Dr. Merrill said. "They represent a huge unmet need. So if we could do trials with these patients and limit the background noise caused by their medications, perhaps we could also see a difference between treatment and placebo. Trials would be easier to recruit, we would see fewer infections, and most importantly, there would be a bigger market for pharma companies to pursue."

Targeting CD22 antigen on B cells

Two randomized, placebo-controlled trials of epratuzumab, a monoclonal antibody targeting CD22 antigen on B cells, had to be terminated when drug supply was interrupted. However, the early findings had shown clinically meaningful improvements in disease activity and corticosteroid sparing. Final results from an open-label extension study for SLE patients previously enrolled in these trials (n = 429), sponsored by UCB Pharma, showed that continued administration of epratuzumab resulted in sustained improvements after a mean four years of treatment, with no new safety signals (Lupus 2013;22[Suppl.]:O25).

Phase II data on blisibimod

Blisibimod, a biologic injected subcutaneously that inhibits B-cell activating factor, or BAFF, was investigated in a phase IIb manufacturer-sponsored trial of 547 patients with anti-dsDNA or anti-nuclear antibodies and SELENA-SLEDAI score of 6 or higher at baseline. Dr. Morton Scheinberg of Rheumatology Hospital Abreu Sodre Pesquisa Clínica, São Paulo, Brazil, led the trial, sponsored by Anthera Pharmaceuticals, in which patients were randomized to one of three doses or placebo. The composite primary endpoint, SRI-5 (defined as a 5-point improvement in SELENA-SLEDAI, no new BILAG A or 2B organ domain scores, and no worsening in Physician’s Global Assessment) was not met because efficacy was not shown in the lower doses. However, more subjects who received the highest dose (200 mg once weekly) met the response criteria starting in week 16 (8%, P = .14), through week 24 (8.2%, P = .15), reaching statistical significance at week 20 (Lupus 2013;22[Suppl.]:O21).

Improving on past trial missteps

One of the coinvestigators on the blisibimod trial, Dr. Richard A. Furie, discussed missteps in the design of earlier studies. "Trials of new biologic therapies have taught us to be humble and logical, and to persevere – we’ve made a lot of mistakes over last 20 years," he told the conference, pointing to a handful of trials in which subjects did not have serologic evidence of disease at baseline. "In my book, if someone is clinically active they should have autoantibodies," he said. "So the rules for entry were changed for all trials."

Dr. Furie, chief of the division of rheumatology and allergy-clinical immunology in the North Shore–LIJ Health System and professor of medicine at Hofstra University, Hempstead, N.Y., said that while inclusion criteria had improved, investigators of biologic agents still had far to go in refining SLE trial endpoints. "No two endpoints are the same – we’ve customized the endpoints and are struggling with extrarenal trials whether it should be a single or composite endpoint, whether it should be based on SLEDAI or BILAG alone or should we use SRI – there is no consensus." Echoing Dr. Merrill, he stressed that background medications were another area in need of increased scrutiny and consensus. "Each trial has handled steroids and immunosuppressants differently," he said.

Dr. Merrill has received support from Genentech. Dr. Furie has received support from Anthera, Genentech, and UCB Pharma. Both rheumatologists have received support from many other companies involved in lupus research and therapy.

BUENOS AIRES – Approved biologic therapies for systematic lupus erythematosus have so far been limited to belimumab, and there has been little compelling trial evidence to date for the effectiveness of abatacept or rituximab in either SLE or lupus nephritis.

Nonetheless, investigators presenting at an international congress on systemic lupus erythematosus gave clinicians reasons to be optimistic about these three biologics currently in clinical use, both on and off label.

Reinterpretation of randomized controlled trial data even from trials that did not meet their primary or secondary endpoints, new registry data, clinical observation, and ongoing trials with better-defined endpoints are producing insights into how and which SLE and lupus nephritis patients might benefit from rituximab, abatacept, or belimumab.

Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm discussed findings from a yet-unpublished registry study of biologics in lupus, to be presented in June at the EULAR annual meeting in Madrid. Dr. van Vollenhoven and colleagues found that rituximab, which had not succeeded in the 2012 LUNAR trial in lupus nephritis patients (Arthritis Rheum. 2012;64:1215-26), was the most frequently used off-label biologic being used in lupus in European countries, with about 1% of lupus patients receiving it. "These are more severe disease patients with more damage who have failed other therapies – it seems to be an option of last resort," Dr. van Vollenhoven said.

Dr. Elizabeth Lightstone, a nephrologist at Imperial College London, argued for a role for rituximab beyond rescue therapy in lupus nephritis. "I think most of us think that rituximab does work," Dr. Lightstone told the conference, and described soon-to-be published results from an observational cohort study (n = 50) of new or relapsed lupus nephritis patients receiving rituximab as a first-line treatment protocol along with mycophenolate mofetil (MMF), with a median follow-up of 163 weeks.

By 12 weeks, 18% of patients saw a complete renal response, which increased to 32% at 26 weeks and 50% at 52 weeks, Dr. Lightstone said. Remarkably, 43 patients who started on this regimen have been managed successfully without oral steroids. Dr. Lightstone said that her U.K.-based nephrology group was about to begin recruiting for a randomized, controlled trial that would compare this rituximab-based regimen with MMF and steroids in 252 lupus nephritis patients.

Dr. Lightstone described the failed LUNAR study as having set the bar too high in its definition of complete renal remission, and having gone too short at only 1 year. "There were a lot of positives in that trial," she said. "The serology normalized significantly; in the exploratory endpoints there was at least a 50% reduction in proteinuria significant in the rituximab group at 78 weeks, so there was divergence beyond one year. The need for immunosuppression was significantly different in week 52 and week 78, and there was a reduction in steroids. And black patients responded better – the trial wasn’t powered to show that as significant, but it looks tantalizing."

She also pointed to a randomized, controlled trial of rituximab vs. standard of care, led by Dr. Frédéric Houssiau of the Université Catholique de Louvain in Brussels that may better define the role of rituximab in lupus nephritis. This trial, which aims to recruit 194 patients and is scheduled to end in 2016, is double the duration of the LUNAR trial, at 104 weeks, and defines complete response as a protein/creatinine ratio of 0.5 or less (compared with 0.2 or less in the LUNAR trial).

Dr. van Vollenhoven told the conference that abatacept was being used very rarely in clinical practice in Europe in either SLE or lupus nephritis. He noted, however, that in a negative trial of abatacept in SLE (Arthritis Rheum. 2010;62:3077-87), patients with polyarthritis were seen to benefit most, and though this did not reach statistical significance, it indicated that abatacept might be appropriate for off-label use in such patients. A post hoc analysis of one failed trial of abatacept in lupus nephritis argued that better-defined response criteria would have shown significant differences between the control and placebo groups (Arthritis Rheum. 2012;64:3660-5); company report PDF. "And there are several interesting trials going on with abatacept suggesting that it could work in combination with cyclophosphamide for lupus nephritis," Dr. van Vollenhoven said. "I don’t think the book is completely closed on this."

While belimumab has been the success story among biologics in SLE, as the first biologic developed and licensed to treat the disease, Dr. van Vollenhoven argued that even belimumab may be given short shrift. In the phase III trial of belimumab in SLE (n = 867), belimumab at 10 mg/kg was associated with significant improvement over placebo in standard lupus disease activity scores (Lancet 2011;377:721-31).

"But with just a 10% difference effect size between the two arms, people say this is a weak effect, making all patients a little better," Dr. van Vollenhoven said. "But there could be at least two other explanations. One is that this is a very good medication, but only for some patients. In practice we would have to figure out who these patients are and that they should be getting this treatment. Another is that in these huge trials there is a lot of static – if you’re measuring with an instrument that’s not very good, you won’t get a strong signal."

Dr. van Vollenhoven said that in his clinical practice, "we have found that the patient who has low complement and anti-DNA antibodies plus active disease and are on steroids have a pretty good likelihood of benefiting from belimumab, and that’s how we have been using it in our practice. And we are seeing good results."

Dr. van Vollenhoven has served as an adviser or consultant for Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Roche, and UCB Pharma. Dr. Lightstone has received support from Genentech, Roche, Biogen Idec, Aspreva, and GlaxoSmithKline.

BUENOS AIRES – Approved biologic therapies for systematic lupus erythematosus have so far been limited to belimumab, and there has been little compelling trial evidence to date for the effectiveness of abatacept or rituximab in either SLE or lupus nephritis.

Nonetheless, investigators presenting at an international congress on systemic lupus erythematosus gave clinicians reasons to be optimistic about these three biologics currently in clinical use, both on and off label.

Reinterpretation of randomized controlled trial data even from trials that did not meet their primary or secondary endpoints, new registry data, clinical observation, and ongoing trials with better-defined endpoints are producing insights into how and which SLE and lupus nephritis patients might benefit from rituximab, abatacept, or belimumab.

Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm discussed findings from a yet-unpublished registry study of biologics in lupus, to be presented in June at the EULAR annual meeting in Madrid. Dr. van Vollenhoven and colleagues found that rituximab, which had not succeeded in the 2012 LUNAR trial in lupus nephritis patients (Arthritis Rheum. 2012;64:1215-26), was the most frequently used off-label biologic being used in lupus in European countries, with about 1% of lupus patients receiving it. "These are more severe disease patients with more damage who have failed other therapies – it seems to be an option of last resort," Dr. van Vollenhoven said.

Dr. Elizabeth Lightstone, a nephrologist at Imperial College London, argued for a role for rituximab beyond rescue therapy in lupus nephritis. "I think most of us think that rituximab does work," Dr. Lightstone told the conference, and described soon-to-be published results from an observational cohort study (n = 50) of new or relapsed lupus nephritis patients receiving rituximab as a first-line treatment protocol along with mycophenolate mofetil (MMF), with a median follow-up of 163 weeks.

By 12 weeks, 18% of patients saw a complete renal response, which increased to 32% at 26 weeks and 50% at 52 weeks, Dr. Lightstone said. Remarkably, 43 patients who started on this regimen have been managed successfully without oral steroids. Dr. Lightstone said that her U.K.-based nephrology group was about to begin recruiting for a randomized, controlled trial that would compare this rituximab-based regimen with MMF and steroids in 252 lupus nephritis patients.

Dr. Lightstone described the failed LUNAR study as having set the bar too high in its definition of complete renal remission, and having gone too short at only 1 year. "There were a lot of positives in that trial," she said. "The serology normalized significantly; in the exploratory endpoints there was at least a 50% reduction in proteinuria significant in the rituximab group at 78 weeks, so there was divergence beyond one year. The need for immunosuppression was significantly different in week 52 and week 78, and there was a reduction in steroids. And black patients responded better – the trial wasn’t powered to show that as significant, but it looks tantalizing."

She also pointed to a randomized, controlled trial of rituximab vs. standard of care, led by Dr. Frédéric Houssiau of the Université Catholique de Louvain in Brussels that may better define the role of rituximab in lupus nephritis. This trial, which aims to recruit 194 patients and is scheduled to end in 2016, is double the duration of the LUNAR trial, at 104 weeks, and defines complete response as a protein/creatinine ratio of 0.5 or less (compared with 0.2 or less in the LUNAR trial).

Dr. van Vollenhoven told the conference that abatacept was being used very rarely in clinical practice in Europe in either SLE or lupus nephritis. He noted, however, that in a negative trial of abatacept in SLE (Arthritis Rheum. 2010;62:3077-87), patients with polyarthritis were seen to benefit most, and though this did not reach statistical significance, it indicated that abatacept might be appropriate for off-label use in such patients. A post hoc analysis of one failed trial of abatacept in lupus nephritis argued that better-defined response criteria would have shown significant differences between the control and placebo groups (Arthritis Rheum. 2012;64:3660-5); company report PDF. "And there are several interesting trials going on with abatacept suggesting that it could work in combination with cyclophosphamide for lupus nephritis," Dr. van Vollenhoven said. "I don’t think the book is completely closed on this."

While belimumab has been the success story among biologics in SLE, as the first biologic developed and licensed to treat the disease, Dr. van Vollenhoven argued that even belimumab may be given short shrift. In the phase III trial of belimumab in SLE (n = 867), belimumab at 10 mg/kg was associated with significant improvement over placebo in standard lupus disease activity scores (Lancet 2011;377:721-31).

"But with just a 10% difference effect size between the two arms, people say this is a weak effect, making all patients a little better," Dr. van Vollenhoven said. "But there could be at least two other explanations. One is that this is a very good medication, but only for some patients. In practice we would have to figure out who these patients are and that they should be getting this treatment. Another is that in these huge trials there is a lot of static – if you’re measuring with an instrument that’s not very good, you won’t get a strong signal."

Dr. van Vollenhoven said that in his clinical practice, "we have found that the patient who has low complement and anti-DNA antibodies plus active disease and are on steroids have a pretty good likelihood of benefiting from belimumab, and that’s how we have been using it in our practice. And we are seeing good results."

Dr. van Vollenhoven has served as an adviser or consultant for Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Roche, and UCB Pharma. Dr. Lightstone has received support from Genentech, Roche, Biogen Idec, Aspreva, and GlaxoSmithKline.

BUENOS AIRES – Approved biologic therapies for systematic lupus erythematosus have so far been limited to belimumab, and there has been little compelling trial evidence to date for the effectiveness of abatacept or rituximab in either SLE or lupus nephritis.

Nonetheless, investigators presenting at an international congress on systemic lupus erythematosus gave clinicians reasons to be optimistic about these three biologics currently in clinical use, both on and off label.

Reinterpretation of randomized controlled trial data even from trials that did not meet their primary or secondary endpoints, new registry data, clinical observation, and ongoing trials with better-defined endpoints are producing insights into how and which SLE and lupus nephritis patients might benefit from rituximab, abatacept, or belimumab.

Dr. Ronald F. van Vollenhoven of the Karolinska Institute in Stockholm discussed findings from a yet-unpublished registry study of biologics in lupus, to be presented in June at the EULAR annual meeting in Madrid. Dr. van Vollenhoven and colleagues found that rituximab, which had not succeeded in the 2012 LUNAR trial in lupus nephritis patients (Arthritis Rheum. 2012;64:1215-26), was the most frequently used off-label biologic being used in lupus in European countries, with about 1% of lupus patients receiving it. "These are more severe disease patients with more damage who have failed other therapies – it seems to be an option of last resort," Dr. van Vollenhoven said.

Dr. Elizabeth Lightstone, a nephrologist at Imperial College London, argued for a role for rituximab beyond rescue therapy in lupus nephritis. "I think most of us think that rituximab does work," Dr. Lightstone told the conference, and described soon-to-be published results from an observational cohort study (n = 50) of new or relapsed lupus nephritis patients receiving rituximab as a first-line treatment protocol along with mycophenolate mofetil (MMF), with a median follow-up of 163 weeks.

By 12 weeks, 18% of patients saw a complete renal response, which increased to 32% at 26 weeks and 50% at 52 weeks, Dr. Lightstone said. Remarkably, 43 patients who started on this regimen have been managed successfully without oral steroids. Dr. Lightstone said that her U.K.-based nephrology group was about to begin recruiting for a randomized, controlled trial that would compare this rituximab-based regimen with MMF and steroids in 252 lupus nephritis patients.

Dr. Lightstone described the failed LUNAR study as having set the bar too high in its definition of complete renal remission, and having gone too short at only 1 year. "There were a lot of positives in that trial," she said. "The serology normalized significantly; in the exploratory endpoints there was at least a 50% reduction in proteinuria significant in the rituximab group at 78 weeks, so there was divergence beyond one year. The need for immunosuppression was significantly different in week 52 and week 78, and there was a reduction in steroids. And black patients responded better – the trial wasn’t powered to show that as significant, but it looks tantalizing."

She also pointed to a randomized, controlled trial of rituximab vs. standard of care, led by Dr. Frédéric Houssiau of the Université Catholique de Louvain in Brussels that may better define the role of rituximab in lupus nephritis. This trial, which aims to recruit 194 patients and is scheduled to end in 2016, is double the duration of the LUNAR trial, at 104 weeks, and defines complete response as a protein/creatinine ratio of 0.5 or less (compared with 0.2 or less in the LUNAR trial).

Dr. van Vollenhoven told the conference that abatacept was being used very rarely in clinical practice in Europe in either SLE or lupus nephritis. He noted, however, that in a negative trial of abatacept in SLE (Arthritis Rheum. 2010;62:3077-87), patients with polyarthritis were seen to benefit most, and though this did not reach statistical significance, it indicated that abatacept might be appropriate for off-label use in such patients. A post hoc analysis of one failed trial of abatacept in lupus nephritis argued that better-defined response criteria would have shown significant differences between the control and placebo groups (Arthritis Rheum. 2012;64:3660-5); company report PDF. "And there are several interesting trials going on with abatacept suggesting that it could work in combination with cyclophosphamide for lupus nephritis," Dr. van Vollenhoven said. "I don’t think the book is completely closed on this."

While belimumab has been the success story among biologics in SLE, as the first biologic developed and licensed to treat the disease, Dr. van Vollenhoven argued that even belimumab may be given short shrift. In the phase III trial of belimumab in SLE (n = 867), belimumab at 10 mg/kg was associated with significant improvement over placebo in standard lupus disease activity scores (Lancet 2011;377:721-31).

"But with just a 10% difference effect size between the two arms, people say this is a weak effect, making all patients a little better," Dr. van Vollenhoven said. "But there could be at least two other explanations. One is that this is a very good medication, but only for some patients. In practice we would have to figure out who these patients are and that they should be getting this treatment. Another is that in these huge trials there is a lot of static – if you’re measuring with an instrument that’s not very good, you won’t get a strong signal."

Dr. van Vollenhoven said that in his clinical practice, "we have found that the patient who has low complement and anti-DNA antibodies plus active disease and are on steroids have a pretty good likelihood of benefiting from belimumab, and that’s how we have been using it in our practice. And we are seeing good results."

Dr. van Vollenhoven has served as an adviser or consultant for Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer, Roche, and UCB Pharma. Dr. Lightstone has received support from Genentech, Roche, Biogen Idec, Aspreva, and GlaxoSmithKline.

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

Most patients with psoriatic arthritis fare better when remaining on a single tumor necrosis factor inhibitor than when switching to a second medication, Norwegian researchers have found.

Karen Fagerli, Ph.D., of the department of rheumatology at Diakonhjemmet Hospital in Oslo, and her colleagues found that patients who switched tumor necrosis factor inhibitor (TNFi) medications had significantly poorer responses in factors like American College of Rheumatology-50 (ACR 50) response and Disease Activity Score-28 (DAS28) remission, compared with those who stayed on one TNFi. Drug-survival rates at 3 years also were lower among patients who changed medications (Ann. Rheum. Dis. 2013 April 5 [doi: 10.1136/annrheumdis-2012-203018]).

Because some (20%-40%) patients showed a response to a second TNFi at 3 months, "our results do not imply that a second TNFi should not be attempted in those who fail their first TNFi, but rather highlight the need for treatments with other mechanisms of action for patients with psoriatic arthritis," Dr. Fagerli and her colleagues wrote.

The investigators studied patient data from the observational NOR-DMARD study, a registry at five centers in Norway of all patients with inflammatory arthropathies starting disease-modifying antirheumatic drugs (DMARDs). Patients in the registry were assessed at baseline and 3, 6, and 12 months after starting treatment. They had annual follow-up visits thereafter.

The researchers included 439 patients with psoriatic arthritis who started their first TNFi between February 2001 and October 2011. They labeled the 95 patients who started a second TNFi as the "switchers," and the remaining 344 patients who stayed on one TNFi as the "nonswitchers." Researchers compared 3-month responses and 3-year drug-survival between switchers and nonswitchers, and within switchers. Among switchers, etanercept (Enbrel) was the most commonly prescribed first TNFi, and adalimumab (Humira) the most commonly prescribed second TNFi.

The switchers receiving their second TNFi had significantly poorer responses by 3 months than the nonswitchers: The ACR 50 response was 22.5% in switchers taking a second TNFi, versus 40% in nonswitchers, and DAS28 remission rates were 28% in switchers taking a second TNFi, versus 54% in nonswitchers.

Researchers also found a trend among the switchers toward poorer responses to the second TNFi, compared with the first. "The estimated 3-year drug-survival was 36% for the second TNFi, compared with 57% for the first TNFi overall," they wrote.

The investigators noted that the comparisons between switchers and nonswitchers could be biased by "some patients still having residual effects of their first TNFi when starting the second, ... but the pattern of poorer response to the second TNFi was consistent for both analytic approaches."

Even though the approach to evaluating effectiveness through the assessment of treatment completers "likely overestimates effectiveness due to discontinuations prior to assessment in poor responders," there was only a small difference in the rate of discontinuation prior to the 3-month assessment between the switchers, who had the poorest response, and the nonswitchers, the investigators said.

The study was supported by the Norwegian South Eastern Health Board. The NOR-DMARD study received funding from Abbott, Amgen, and other companies. Dr. Fagerli reported having received speaker’s honoraria from Abbott and Pfizer. Other authors reported financial ties to manufacturers of TNF inhibitors and other biologics.

MAUI, HAWAII – The strong association between psoriasis and cutaneous T-cell lymphoma warrants a low threshold for skin biopsy in psoriasis patients, particularly since the two diseases can be tough to differentiate, experts emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Indeed, skin biopsy is appropriate in any psoriasis patient with atypical features or psoriasis that isn’t responding to treatment, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia.

"I’ve found that my psoriasis patients actually like to be biopsied. They’ve been living with their disease for an average of 20 years, and they’re curious," he said. "And they’re also suspicious. They wonder, ‘How could I have this for 20 years and it’s still here?’ They’re worried that it’s really cancer or something else. So my patients never decline a biopsy of psoriasis," he said.

The literature on psoriasis and solid malignancies is "a mess," with some observational studies showing a positive association and others not, Dr. Gelfand noted.

In contrast, the studies looking at psoriasis and cutaneous T-cell lymphoma (CTCL) have been consistently positive. Case in point: when Dr. Gelfand and colleagues turned to the U.K. General Practice Research Database to study more than 153,000 psoriasis patients and nearly 800,000 controls, they found participants with mild psoriasis had a 4.1-fold increased relative risk of developing CTCL, while those with severe psoriasis had a 10.75-fold increased risk (J. Invest. Dermatol. 2006;126:2194-201).

One limitation of large, observational studies is that it’s hard to know whether some psoriasis patients who developed CTCL were initially misdiagnosed and actually had CTCL all along, Dr. Gelfand said.

"We have a large lymphoma study group at Penn, and we see all kinds: we see some patients who clearly had psoriasis for many years and then developed erythrodermic CTCL, and we have people who clearly were misdiagnosed as having psoriasis," he said.

Whether the increased lymphoma risk is caused by psoriasis itself, as opposed to the chronic use of immunosuppressive drugs employed in treating the skin disease, remains uncertain. To date, the studies are mostly reassuring that the psoriasis medications don’t significantly increase the risk. One thing that is clear, however, is that CTCL can progress very rapidly in a patient who is on potent immunosuppressive therapy for what is mistakenly thought to be psoriasis.

"The patient with tumor-stage mycosis fungoides is not a person you want to hit with a TNF inhibitor," Dr. Gelfand observed.

The distinction between severe psoriasis and CTCL can be tricky, according to veteran psoriasis researcher Dr. Craig L. Leonardi of Saint Louis University.

"In the last 13 years, while we’ve been developing the biologic agents, every now and then we’ll get a patient in a research trial who actually has CTCL. This is in an environment where patients are being examined closely, and yet the clinician is totally fooled by it," Dr. Leonardi said. "These drugs have evolved to the point that we get PASI-75 responses in the 70%-85% range. Most patients will have a rocking experience on these medications. So it’s a good general rule that if you find somebody who doesn’t respond, it’s time to start thinking about other diagnoses."

When Dr. Gelfand’s suspicions are raised, he typically biopsies one or two representative lesions after the patient has been off of topical steroids for at least a week, since the medication can reduce the epidermal infiltrate.

Be cautious if the histologic specimen is going to be read by a general pathologist. The situation is fairly straightforward if the report comes back as unequivocally psoriasis or CTCL. But if the report says, ‘psoriasiform dermatitis NOS’ it’s appropriate to insist that a dermatopathologist takes a look at the slides, Dr. Gelfand said.

"A lot of malpractice cases come across my desk, and ‘failure to diagnose’ is always a big one," said Dr. Guy F. Webster of Thomas Jefferson University, Philadelphia.

"It’s not always melanoma, either," he continued. "The story is always that somebody had a rash for a long time. It looked like eczema, psoriasis, whatever. And the physician treated it without ever questioning the diagnosis when the patient didn’t get better."

Dr. Alan Menter noted convincing evidence that, at pretreatment baseline, psoriasis patients, like those with rheumatoid arthritis, have a slightly increased risk of lymphoma.

"It’s kind of sensitive to talk to patients about the cancer issue. They all ask, ‘Is there a chance you’ll cause cancer by giving me this biologic drug?’ You have to gently tell them they are already at slightly increased risk," Dr. Menter said.

"Is the use of an anti-TNF agent going to increase that risk? The answer is that in all of the more than 2 million patients who’ve been treated with TNF inhibitors, there does not appear to be a statistical increase above the baseline risk," said Dr. Menter of Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

SDEF and this news organization are owned by the same parent company. Dr. Menter, Dr. Gelfand, Dr. Webster, and Dr. Leonardi have received research funds and/or served as consultants to numerous pharmaceutical companies.

bjancin@frontlinemedcom.com

MAUI, HAWAII – The strong association between psoriasis and cutaneous T-cell lymphoma warrants a low threshold for skin biopsy in psoriasis patients, particularly since the two diseases can be tough to differentiate, experts emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Indeed, skin biopsy is appropriate in any psoriasis patient with atypical features or psoriasis that isn’t responding to treatment, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia.

"I’ve found that my psoriasis patients actually like to be biopsied. They’ve been living with their disease for an average of 20 years, and they’re curious," he said. "And they’re also suspicious. They wonder, ‘How could I have this for 20 years and it’s still here?’ They’re worried that it’s really cancer or something else. So my patients never decline a biopsy of psoriasis," he said.

The literature on psoriasis and solid malignancies is "a mess," with some observational studies showing a positive association and others not, Dr. Gelfand noted.

In contrast, the studies looking at psoriasis and cutaneous T-cell lymphoma (CTCL) have been consistently positive. Case in point: when Dr. Gelfand and colleagues turned to the U.K. General Practice Research Database to study more than 153,000 psoriasis patients and nearly 800,000 controls, they found participants with mild psoriasis had a 4.1-fold increased relative risk of developing CTCL, while those with severe psoriasis had a 10.75-fold increased risk (J. Invest. Dermatol. 2006;126:2194-201).

One limitation of large, observational studies is that it’s hard to know whether some psoriasis patients who developed CTCL were initially misdiagnosed and actually had CTCL all along, Dr. Gelfand said.

"We have a large lymphoma study group at Penn, and we see all kinds: we see some patients who clearly had psoriasis for many years and then developed erythrodermic CTCL, and we have people who clearly were misdiagnosed as having psoriasis," he said.

Whether the increased lymphoma risk is caused by psoriasis itself, as opposed to the chronic use of immunosuppressive drugs employed in treating the skin disease, remains uncertain. To date, the studies are mostly reassuring that the psoriasis medications don’t significantly increase the risk. One thing that is clear, however, is that CTCL can progress very rapidly in a patient who is on potent immunosuppressive therapy for what is mistakenly thought to be psoriasis.

"The patient with tumor-stage mycosis fungoides is not a person you want to hit with a TNF inhibitor," Dr. Gelfand observed.

The distinction between severe psoriasis and CTCL can be tricky, according to veteran psoriasis researcher Dr. Craig L. Leonardi of Saint Louis University.

"In the last 13 years, while we’ve been developing the biologic agents, every now and then we’ll get a patient in a research trial who actually has CTCL. This is in an environment where patients are being examined closely, and yet the clinician is totally fooled by it," Dr. Leonardi said. "These drugs have evolved to the point that we get PASI-75 responses in the 70%-85% range. Most patients will have a rocking experience on these medications. So it’s a good general rule that if you find somebody who doesn’t respond, it’s time to start thinking about other diagnoses."

When Dr. Gelfand’s suspicions are raised, he typically biopsies one or two representative lesions after the patient has been off of topical steroids for at least a week, since the medication can reduce the epidermal infiltrate.

Be cautious if the histologic specimen is going to be read by a general pathologist. The situation is fairly straightforward if the report comes back as unequivocally psoriasis or CTCL. But if the report says, ‘psoriasiform dermatitis NOS’ it’s appropriate to insist that a dermatopathologist takes a look at the slides, Dr. Gelfand said.

"A lot of malpractice cases come across my desk, and ‘failure to diagnose’ is always a big one," said Dr. Guy F. Webster of Thomas Jefferson University, Philadelphia.

"It’s not always melanoma, either," he continued. "The story is always that somebody had a rash for a long time. It looked like eczema, psoriasis, whatever. And the physician treated it without ever questioning the diagnosis when the patient didn’t get better."

Dr. Alan Menter noted convincing evidence that, at pretreatment baseline, psoriasis patients, like those with rheumatoid arthritis, have a slightly increased risk of lymphoma.

"It’s kind of sensitive to talk to patients about the cancer issue. They all ask, ‘Is there a chance you’ll cause cancer by giving me this biologic drug?’ You have to gently tell them they are already at slightly increased risk," Dr. Menter said.

"Is the use of an anti-TNF agent going to increase that risk? The answer is that in all of the more than 2 million patients who’ve been treated with TNF inhibitors, there does not appear to be a statistical increase above the baseline risk," said Dr. Menter of Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

SDEF and this news organization are owned by the same parent company. Dr. Menter, Dr. Gelfand, Dr. Webster, and Dr. Leonardi have received research funds and/or served as consultants to numerous pharmaceutical companies.

bjancin@frontlinemedcom.com

MAUI, HAWAII – The strong association between psoriasis and cutaneous T-cell lymphoma warrants a low threshold for skin biopsy in psoriasis patients, particularly since the two diseases can be tough to differentiate, experts emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Indeed, skin biopsy is appropriate in any psoriasis patient with atypical features or psoriasis that isn’t responding to treatment, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia.

"I’ve found that my psoriasis patients actually like to be biopsied. They’ve been living with their disease for an average of 20 years, and they’re curious," he said. "And they’re also suspicious. They wonder, ‘How could I have this for 20 years and it’s still here?’ They’re worried that it’s really cancer or something else. So my patients never decline a biopsy of psoriasis," he said.

The literature on psoriasis and solid malignancies is "a mess," with some observational studies showing a positive association and others not, Dr. Gelfand noted.

In contrast, the studies looking at psoriasis and cutaneous T-cell lymphoma (CTCL) have been consistently positive. Case in point: when Dr. Gelfand and colleagues turned to the U.K. General Practice Research Database to study more than 153,000 psoriasis patients and nearly 800,000 controls, they found participants with mild psoriasis had a 4.1-fold increased relative risk of developing CTCL, while those with severe psoriasis had a 10.75-fold increased risk (J. Invest. Dermatol. 2006;126:2194-201).

One limitation of large, observational studies is that it’s hard to know whether some psoriasis patients who developed CTCL were initially misdiagnosed and actually had CTCL all along, Dr. Gelfand said.

"We have a large lymphoma study group at Penn, and we see all kinds: we see some patients who clearly had psoriasis for many years and then developed erythrodermic CTCL, and we have people who clearly were misdiagnosed as having psoriasis," he said.

Whether the increased lymphoma risk is caused by psoriasis itself, as opposed to the chronic use of immunosuppressive drugs employed in treating the skin disease, remains uncertain. To date, the studies are mostly reassuring that the psoriasis medications don’t significantly increase the risk. One thing that is clear, however, is that CTCL can progress very rapidly in a patient who is on potent immunosuppressive therapy for what is mistakenly thought to be psoriasis.

"The patient with tumor-stage mycosis fungoides is not a person you want to hit with a TNF inhibitor," Dr. Gelfand observed.

The distinction between severe psoriasis and CTCL can be tricky, according to veteran psoriasis researcher Dr. Craig L. Leonardi of Saint Louis University.

"In the last 13 years, while we’ve been developing the biologic agents, every now and then we’ll get a patient in a research trial who actually has CTCL. This is in an environment where patients are being examined closely, and yet the clinician is totally fooled by it," Dr. Leonardi said. "These drugs have evolved to the point that we get PASI-75 responses in the 70%-85% range. Most patients will have a rocking experience on these medications. So it’s a good general rule that if you find somebody who doesn’t respond, it’s time to start thinking about other diagnoses."

When Dr. Gelfand’s suspicions are raised, he typically biopsies one or two representative lesions after the patient has been off of topical steroids for at least a week, since the medication can reduce the epidermal infiltrate.

Be cautious if the histologic specimen is going to be read by a general pathologist. The situation is fairly straightforward if the report comes back as unequivocally psoriasis or CTCL. But if the report says, ‘psoriasiform dermatitis NOS’ it’s appropriate to insist that a dermatopathologist takes a look at the slides, Dr. Gelfand said.

"A lot of malpractice cases come across my desk, and ‘failure to diagnose’ is always a big one," said Dr. Guy F. Webster of Thomas Jefferson University, Philadelphia.

"It’s not always melanoma, either," he continued. "The story is always that somebody had a rash for a long time. It looked like eczema, psoriasis, whatever. And the physician treated it without ever questioning the diagnosis when the patient didn’t get better."

Dr. Alan Menter noted convincing evidence that, at pretreatment baseline, psoriasis patients, like those with rheumatoid arthritis, have a slightly increased risk of lymphoma.

"It’s kind of sensitive to talk to patients about the cancer issue. They all ask, ‘Is there a chance you’ll cause cancer by giving me this biologic drug?’ You have to gently tell them they are already at slightly increased risk," Dr. Menter said.

"Is the use of an anti-TNF agent going to increase that risk? The answer is that in all of the more than 2 million patients who’ve been treated with TNF inhibitors, there does not appear to be a statistical increase above the baseline risk," said Dr. Menter of Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

SDEF and this news organization are owned by the same parent company. Dr. Menter, Dr. Gelfand, Dr. Webster, and Dr. Leonardi have received research funds and/or served as consultants to numerous pharmaceutical companies.

bjancin@frontlinemedcom.com

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

NEW YORK – Obesity appears to reduce response to anti–tumor necrosis factor–alpha treatment in individuals with psoriatic arthritis, but weight loss can improve it, according to a review of two studies by Dr. Christopher T. Ritchlin.

"These data convincingly show that if we talk to our patients and tell them to lose weight, it can have an impact on how their PsA [psoriatic arthritis] therapies are going to work," Dr. Ritchlin, director of the Translational Immunology Research Center at the University of Rochester (N.Y.), said at a meeting sponsored by New York University.

Dr. Ritchlin said these results fit in with previous epidemiologic studies that show that as body mass index goes up, so does the risk for both psoriasis and PsA (Arch. Intern. Med. 2009;167:1670-5 and Ann. Rheum. Dis. 2012;71:1273-7).

These data support a link between obesity-related chronic tissue inflammation and development of some rheumatic diseases, such as arthritis in psoriatic patients. These same inflammatory processes may also interfere with good clinical response to biologic agents.

In a study published by Dr. Matteo Nicola di Minno of Federico II University in Naples, Italy, and his colleagues, individuals with a BMI in the 30-35 kg/m² range with PsA had a nearly fourfold increased risk of not responding well to treatment with tumor necrosis factor–alpha inhibitors (TNFis). The risk of a poor response rose more than fivefold for those whose BMIs greater than 35 kg/m² (Arthritis Care Res. 2013;65:141-7).

The study prospectively followed PsA patients with active disease for 24 months who were starting TNFi therapy (30% adalimumab, 41% etanercept, 29% infliximab). The group comprised 135 obese patients (BMI greater than 30 kg/m²) and 135 controls of normal weight. The primary outcome was achievement of minimal disease activity (MDA), which meant they fulfilled five of seven outcome measures: one or fewer tender joints, one or fewer swollen joints, a score of 1 or less on the Psoriasis Area and Severity Index or body surface area = 3, a score of 15 or less on a visual analog scale (VAS) for pain, a score of 20 or less on a patient global disease severity VAS score, a score on the Health Assessment Questionnaire of 0.5 or less, or one or fewer tender entheseal points.

After 12 months, only 98 (36%) of the total group reached MDA. "What the results showed was that the odds of not achieving MDA were directly related to increased BMI," Dr. Ritchlin said.

Significantly more of the patients who did not achieve MDA were obese (64% vs. 25.5%, P less than .001). After adjustment for other variables, obesity was found to incur a nearly fivefold risk of poor response to therapy (hazard ratio 4.90, 95% confidence interval [CI] 3.04-7.87). The hazard ratios were 3.98 for those with BMI of 30-35 kg/m² and 5.4 for those with BMI greater than 35 kg/m² (both P less than .001). Among the 98 PsA patients who had achieved MDA by 12 months, those who were obese had a poor probability of sustaining MDA when tested at 24 months, according to Dr. di Minno.

In a follow-up study presented at the 2012 EULAR meeting (Ann. Rheum. Dis. 2012;71[Suppl. 3]:109), Dr. di Minno addressed the question of whether weight loss in obese PsA patients would improve treatment response. In this study, 138 obese PsA patients were divided into two groups of 69 patients each. One group received a hypocaloric diet and the controls followed a normal diet.

After 6 months, those who lost 10% of their BMI or more were almost five times more likely to achieve MDA (HR 4.79, P = .002). Those who lost 5%-10% of their BMI were twice as likely as were controls to reach MDA.

Dr. Ritchlin said that he had no relevant disclosures.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

Use of all glucocorticoids is associated with a two- to threefold increased risk of venous thromboembolism, depending on the type of glucocorticoid, the route of administration, and other factors, according to a report published online April 1 in JAMA Internal Medicine.

Systemic glucocorticoids, as compared with inhaled ones or glucocorticoids that act on the intestines, were associated with the highest risk of VTE. New use was linked to higher risk than continuing or past use, and the VTE risk increased as the dose of glucocorticoids increased, said Sigrun A. Johannesdottir of the department of clinical epidemiology, Aarhus (the Netherlands) University Hospital, and her associates.

These findings are from a population-based case-control study, which cannot prove a cause-and-effect relationship. Moreover, it is difficult to statistically account for all the confounding effects of patients’ underlying disease – the reason they were taking glucocorticoids in the first place – because such disorders raise the risk of VTE directly or cause immobility that in turn can lead to VTE.

However, the timing of this adverse effect, the strength of the association across all types of glucocorticoids, and the fact that the association persisted after the data were adjusted to account for multiple confounders all "increase our confidence that the results reflect a true biological effect," the investigators said.

"Clinicians should be aware of this association," they noted.

Ms. Johannesdottir and her colleagues used data from several Danish national medical registries to identify all adults who were diagnosed with VTE in Denmark in 2005-2012, all patients who filled prescriptions for glucocorticoids during the study period, and all indications for the drugs as well as all relevant comorbidities. They matched 10 control subjects for age and sex from the general population to each study subject.

A total of 38,765 VTE cases and 387,650 controls were included in this study. The median age was 67 years, and slightly more than half of those studied were women.

All glucocorticoid users were found to be at increased risk for VTE, particularly for pulmonary embolism, compared with nonusers, the researchers said.

Systemic glucocorticoids, including betamethasone, methylprednisolone, prednisolone, prednisone, triamcinolone, and hydrocortisone, raised VTE risk to the highest degree. (No patients filled prescriptions for dexamethasone in this study.)

Inhaled corticosteroids and corticosteroids that act on the intestines also raised VTE risk significantly. Among the systemic glucocorticoids, prednisolone and prednisone raised VTE risk the most.

New use of glucocorticoids was associated with the highest risk of VTE, but current use, continuing use, and former use also raised the risk significantly. Oral formulations were associated with the highest risk of VTE, but injectable formulations also raised the risk significantly, Ms. Johannesdottir and her associates reported (JAMA Intern. Med. 2013 April 1 [doi:10.1001/jamainternmed.2013.122]).

In particular, new use of systemic glucocorticoids was associated with the highest risk for VTE, with an estimated incidence rate ratio of 3.06, compared with nonuse of glucocorticoids.

The risk of VTE also rose with increasing cumulative doses of all glucocorticoids.

In further analyses, elevated risk for VTE persisted across all the subgroups that were examined.

The findings did not change appreciably in a sensitivity analysis that included only subjects who took glucocorticoids for at least 5 years.

"The temporality of the association (i.e., the strongest effect at initiation of therapy and the absence of an effect after discontinuation) is in line with an effect on coagulation," Ms. Johannesdottir and her associates said.

This study was supported by the Clinical Epidemiological Research Foundation at Aarhus University Hospital. No relevant conflicts of interest were reported.

WAILEA, HAWAII – While psoriasis experts typically emphasize the disease’s chronic nature and the importance of effective long-term therapy, in reality the first big question when a patient presents to the office should be, ‘What’s the urgency of treatment?’ according to Dr. Kenneth B. Gordon, professor of dermatology at Northwestern University, Chicago.

Two patients can have equally extensive disease yet dissimilar treatment urgencies – and different treatments of choice as a result, he said at the Hawaii Dermatology Seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

The list of preferred medications for patients with high treatment urgency is short: "When you need to get people better fast, infliximab and cyclosporine are the go-to drugs," the dermatologist stressed.

Insurance companies will often insist that a patient try methotrexate before resorting to a far costlier biologic agent. That’s unreasonable when the treatment urgency is high.

"Methotrexate doesn’t have a high enough level of predictability or efficacy of response. Additionally, it takes a long time to act. When someone is acutely ill, you don’t want to have to wait 16 weeks to figure out what’s the highest level of efficacy you’re going to get. You want to know that answer in 10 weeks, like you do with infliximab. Infliximab is a wonderful short-term therapy for patients who have urgent disease. And with cyclosporine you see effects in 4-8 weeks," Dr. Gordon continued.

He noted that in the open-label RESTORE 1 trial, in which 868 psoriasis patients were randomized to infliximab or methotrexate, the PASI-75 response rate at week 6 in the infliximab group was already close to 60%. By week 10, the PASI-75 rate was 75% in the infliximab group and 27% in the methotrexate group (Br. J. Dermatol. 2011;165:1109-17).

The main safety concern with cyclosporine is renal toxicity, which doesn’t emerge as a real problem until after about a year on the drug, Dr. Gordon said. The safety concerns associated with short-term use (6-8 weeks) to treat an acute exacerbation of psoriasis before transitioning to a different medication are modest, and limited to relatively uncommon increases in blood pressure.

Factors that might raise a patient’s treatment urgency level range from sleep deprivation because of psoriasis pain and itching to workplace hassles because of extensive sick leave, to an important public appearance scheduled within 6-8 weeks.

Session moderator Dr. Craig L. Leonardi remarked that getting payer approval for infliximab often takes a month.

"Unless you’re university based, it’s unlikely you’re going to get infliximab fast, so cyclosporine becomes a real mainstay of treatment when it’s hot and bothersome psoriasis," he said. "And it’s the treatment of choice for psoriasis during pregnancy, absolutely. It’s category C, but there’s a lot of experience with it in the transplant population," noted Dr. Leonardi of St. Louis University.

Dr. Gordon also described a clinical scenario completely different from high treatment urgency – the patient with extensive, yet stable disease. In such a case, the priority is to select a drug the patient can tolerate for a year or more, with good long-term safety and little loss of efficacy over time.

The therapeutic responses to infliximab and adalimumab tend to fade over time, but the majority of patients still do well after 1-3 years of continuous therapy, said Dr. Gordon. His analysis of the phase III REVEAL trial extension showed that 83% of patients with at least a PASI-75 response through the first 33 weeks of adalimumab therapy continued to have a PASI-75 or better response through 100 weeks, and 76% of the original responders were still in that category after 160 weeks of therapy (J. Am. Acad. Dermatol. 2012;66:241-51).

The data on the long-term safety of antitumor necrosis factor agents are extensive and largely reassuring, Dr. Gordon noted.

"I make the argument that there is more known about anti-TNF therapy in terms of safety than any other medicines ever," Dr. Gordon said. Much of the data come courtesy of Europe, where most patients are able to get on anti-TNF therapy only if a physician enrolls them in a registry, he added.

The primary safety risk posed by biologic therapy is serious infections, in Dr. Gordon’s opinion. The collective registry experience in rheumatoid arthritis patients suggests that risk is about 20% greater than in patients on methotrexate, and this risk appears to be stable over time. But it’s probably a mistake to extrapolate from the rheumatologic experience to psoriasis, Dr. Gordon said. He and his colleagues have shown that rheumatoid arthritis patients on biologic therapy tend to be older and more likely to be on concomitant systemic corticosteroids and other immunosuppressive drugs than are psoriasis patients (Ann. Rheum. Dis. 2009;68:1863-9). More data on the risks of biologic therapies in psoriasis patients are anticipated from PSOLAR and other large ongoing patient registries, he said.

A key issue in long-term therapy is the desire of many psoriasis patients to see how they will fare without medication, and the issue has been studied extensively in clinical trials. Dr. Gordon tells patients who would like to discontinue therapy until they relapse, and that there is a one in three chance that they won’t improve upon retreatment. These patients would then need to try another medication. Today there are other medications, and there will likely be more in the coming years, he said.

"But there is a group of patients – and I think we all have them – who are just burning through these medications and don’t respond as well as they did before. So I think we have to be careful and try to convince patients they might be better off staying on their medicine," he said.

SDEF and this news organization are owned by the same parent company.

Dr. Gordon reported receiving research support and/or serving as a consultant to several pharmaceutical companies including Abbott, Amgen, Lilly, and Pfizer.

bjancin@frontlinlinemedcom.com

WAILEA, HAWAII – While psoriasis experts typically emphasize the disease’s chronic nature and the importance of effective long-term therapy, in reality the first big question when a patient presents to the office should be, ‘What’s the urgency of treatment?’ according to Dr. Kenneth B. Gordon, professor of dermatology at Northwestern University, Chicago.

Two patients can have equally extensive disease yet dissimilar treatment urgencies – and different treatments of choice as a result, he said at the Hawaii Dermatology Seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

The list of preferred medications for patients with high treatment urgency is short: "When you need to get people better fast, infliximab and cyclosporine are the go-to drugs," the dermatologist stressed.

Insurance companies will often insist that a patient try methotrexate before resorting to a far costlier biologic agent. That’s unreasonable when the treatment urgency is high.

"Methotrexate doesn’t have a high enough level of predictability or efficacy of response. Additionally, it takes a long time to act. When someone is acutely ill, you don’t want to have to wait 16 weeks to figure out what’s the highest level of efficacy you’re going to get. You want to know that answer in 10 weeks, like you do with infliximab. Infliximab is a wonderful short-term therapy for patients who have urgent disease. And with cyclosporine you see effects in 4-8 weeks," Dr. Gordon continued.

He noted that in the open-label RESTORE 1 trial, in which 868 psoriasis patients were randomized to infliximab or methotrexate, the PASI-75 response rate at week 6 in the infliximab group was already close to 60%. By week 10, the PASI-75 rate was 75% in the infliximab group and 27% in the methotrexate group (Br. J. Dermatol. 2011;165:1109-17).

The main safety concern with cyclosporine is renal toxicity, which doesn’t emerge as a real problem until after about a year on the drug, Dr. Gordon said. The safety concerns associated with short-term use (6-8 weeks) to treat an acute exacerbation of psoriasis before transitioning to a different medication are modest, and limited to relatively uncommon increases in blood pressure.

Factors that might raise a patient’s treatment urgency level range from sleep deprivation because of psoriasis pain and itching to workplace hassles because of extensive sick leave, to an important public appearance scheduled within 6-8 weeks.

Session moderator Dr. Craig L. Leonardi remarked that getting payer approval for infliximab often takes a month.

"Unless you’re university based, it’s unlikely you’re going to get infliximab fast, so cyclosporine becomes a real mainstay of treatment when it’s hot and bothersome psoriasis," he said. "And it’s the treatment of choice for psoriasis during pregnancy, absolutely. It’s category C, but there’s a lot of experience with it in the transplant population," noted Dr. Leonardi of St. Louis University.

Dr. Gordon also described a clinical scenario completely different from high treatment urgency – the patient with extensive, yet stable disease. In such a case, the priority is to select a drug the patient can tolerate for a year or more, with good long-term safety and little loss of efficacy over time.

The therapeutic responses to infliximab and adalimumab tend to fade over time, but the majority of patients still do well after 1-3 years of continuous therapy, said Dr. Gordon. His analysis of the phase III REVEAL trial extension showed that 83% of patients with at least a PASI-75 response through the first 33 weeks of adalimumab therapy continued to have a PASI-75 or better response through 100 weeks, and 76% of the original responders were still in that category after 160 weeks of therapy (J. Am. Acad. Dermatol. 2012;66:241-51).

The data on the long-term safety of antitumor necrosis factor agents are extensive and largely reassuring, Dr. Gordon noted.

"I make the argument that there is more known about anti-TNF therapy in terms of safety than any other medicines ever," Dr. Gordon said. Much of the data come courtesy of Europe, where most patients are able to get on anti-TNF therapy only if a physician enrolls them in a registry, he added.

The primary safety risk posed by biologic therapy is serious infections, in Dr. Gordon’s opinion. The collective registry experience in rheumatoid arthritis patients suggests that risk is about 20% greater than in patients on methotrexate, and this risk appears to be stable over time. But it’s probably a mistake to extrapolate from the rheumatologic experience to psoriasis, Dr. Gordon said. He and his colleagues have shown that rheumatoid arthritis patients on biologic therapy tend to be older and more likely to be on concomitant systemic corticosteroids and other immunosuppressive drugs than are psoriasis patients (Ann. Rheum. Dis. 2009;68:1863-9). More data on the risks of biologic therapies in psoriasis patients are anticipated from PSOLAR and other large ongoing patient registries, he said.

A key issue in long-term therapy is the desire of many psoriasis patients to see how they will fare without medication, and the issue has been studied extensively in clinical trials. Dr. Gordon tells patients who would like to discontinue therapy until they relapse, and that there is a one in three chance that they won’t improve upon retreatment. These patients would then need to try another medication. Today there are other medications, and there will likely be more in the coming years, he said.

"But there is a group of patients – and I think we all have them – who are just burning through these medications and don’t respond as well as they did before. So I think we have to be careful and try to convince patients they might be better off staying on their medicine," he said.

SDEF and this news organization are owned by the same parent company.

Dr. Gordon reported receiving research support and/or serving as a consultant to several pharmaceutical companies including Abbott, Amgen, Lilly, and Pfizer.

bjancin@frontlinlinemedcom.com

WAILEA, HAWAII – While psoriasis experts typically emphasize the disease’s chronic nature and the importance of effective long-term therapy, in reality the first big question when a patient presents to the office should be, ‘What’s the urgency of treatment?’ according to Dr. Kenneth B. Gordon, professor of dermatology at Northwestern University, Chicago.

Two patients can have equally extensive disease yet dissimilar treatment urgencies – and different treatments of choice as a result, he said at the Hawaii Dermatology Seminar, sponsored by the Global Academy for Medical Education/Skin Disease Education Foundation.

The list of preferred medications for patients with high treatment urgency is short: "When you need to get people better fast, infliximab and cyclosporine are the go-to drugs," the dermatologist stressed.

Insurance companies will often insist that a patient try methotrexate before resorting to a far costlier biologic agent. That’s unreasonable when the treatment urgency is high.

"Methotrexate doesn’t have a high enough level of predictability or efficacy of response. Additionally, it takes a long time to act. When someone is acutely ill, you don’t want to have to wait 16 weeks to figure out what’s the highest level of efficacy you’re going to get. You want to know that answer in 10 weeks, like you do with infliximab. Infliximab is a wonderful short-term therapy for patients who have urgent disease. And with cyclosporine you see effects in 4-8 weeks," Dr. Gordon continued.

He noted that in the open-label RESTORE 1 trial, in which 868 psoriasis patients were randomized to infliximab or methotrexate, the PASI-75 response rate at week 6 in the infliximab group was already close to 60%. By week 10, the PASI-75 rate was 75% in the infliximab group and 27% in the methotrexate group (Br. J. Dermatol. 2011;165:1109-17).

The main safety concern with cyclosporine is renal toxicity, which doesn’t emerge as a real problem until after about a year on the drug, Dr. Gordon said. The safety concerns associated with short-term use (6-8 weeks) to treat an acute exacerbation of psoriasis before transitioning to a different medication are modest, and limited to relatively uncommon increases in blood pressure.

Factors that might raise a patient’s treatment urgency level range from sleep deprivation because of psoriasis pain and itching to workplace hassles because of extensive sick leave, to an important public appearance scheduled within 6-8 weeks.

Session moderator Dr. Craig L. Leonardi remarked that getting payer approval for infliximab often takes a month.

"Unless you’re university based, it’s unlikely you’re going to get infliximab fast, so cyclosporine becomes a real mainstay of treatment when it’s hot and bothersome psoriasis," he said. "And it’s the treatment of choice for psoriasis during pregnancy, absolutely. It’s category C, but there’s a lot of experience with it in the transplant population," noted Dr. Leonardi of St. Louis University.

Dr. Gordon also described a clinical scenario completely different from high treatment urgency – the patient with extensive, yet stable disease. In such a case, the priority is to select a drug the patient can tolerate for a year or more, with good long-term safety and little loss of efficacy over time.

The therapeutic responses to infliximab and adalimumab tend to fade over time, but the majority of patients still do well after 1-3 years of continuous therapy, said Dr. Gordon. His analysis of the phase III REVEAL trial extension showed that 83% of patients with at least a PASI-75 response through the first 33 weeks of adalimumab therapy continued to have a PASI-75 or better response through 100 weeks, and 76% of the original responders were still in that category after 160 weeks of therapy (J. Am. Acad. Dermatol. 2012;66:241-51).

The data on the long-term safety of antitumor necrosis factor agents are extensive and largely reassuring, Dr. Gordon noted.

"I make the argument that there is more known about anti-TNF therapy in terms of safety than any other medicines ever," Dr. Gordon said. Much of the data come courtesy of Europe, where most patients are able to get on anti-TNF therapy only if a physician enrolls them in a registry, he added.

The primary safety risk posed by biologic therapy is serious infections, in Dr. Gordon’s opinion. The collective registry experience in rheumatoid arthritis patients suggests that risk is about 20% greater than in patients on methotrexate, and this risk appears to be stable over time. But it’s probably a mistake to extrapolate from the rheumatologic experience to psoriasis, Dr. Gordon said. He and his colleagues have shown that rheumatoid arthritis patients on biologic therapy tend to be older and more likely to be on concomitant systemic corticosteroids and other immunosuppressive drugs than are psoriasis patients (Ann. Rheum. Dis. 2009;68:1863-9). More data on the risks of biologic therapies in psoriasis patients are anticipated from PSOLAR and other large ongoing patient registries, he said.

A key issue in long-term therapy is the desire of many psoriasis patients to see how they will fare without medication, and the issue has been studied extensively in clinical trials. Dr. Gordon tells patients who would like to discontinue therapy until they relapse, and that there is a one in three chance that they won’t improve upon retreatment. These patients would then need to try another medication. Today there are other medications, and there will likely be more in the coming years, he said.

"But there is a group of patients – and I think we all have them – who are just burning through these medications and don’t respond as well as they did before. So I think we have to be careful and try to convince patients they might be better off staying on their medicine," he said.

SDEF and this news organization are owned by the same parent company.

Dr. Gordon reported receiving research support and/or serving as a consultant to several pharmaceutical companies including Abbott, Amgen, Lilly, and Pfizer.

bjancin@frontlinlinemedcom.com

MAUI, HAWAII – Routine screening for hepatitis B and C has become a must prior to initiation of chronic immunosuppressive therapy for psoriasis, Dr. Craig L. Leonardi said.

"Universal screening for hepatitis B and hepatitis C infection is not optional in 2013," he stressed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

That said, professional society guidelines are at odds and in flux on this issue. The American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Centers for Disease Control and Prevention all recommend routine screening for hepatitis B surface antigen and hepatitis B core antibody prior to initiation of immunosuppressive therapy. The CDC also recommends universal pretreatment testing for antibody to hepatitis B surface antibody.

In contrast, the American College of Rheumatology recommends HBV screening only in high-risk patients and those treated with specific drugs (Arthritis Rheum. 2008;59:762-84).

For now, the American Academy of Dermatology guidelines take a middle-of-the-road position, which Dr. Leonardi said he finds unconvincing. The current guidelines recommend hepatitis B screening in the appropriate setting (J. Am. Acad. Dermatol. 2008;58:826-50).

"Well, the appropriate setting is when you’re going to use immunosuppressive agents," he asserted. "So I think we all need to start ordering these tests and be on the lookout for the problem. Prophylactic antiviral therapy may be more than the average dermatologist wants to take on. Nonetheless, you want to do the testing and then refer affected patients to an experienced hepatology center."

Chronic immunosuppressive therapy for psoriasis encompasses all the biologics agents – the tumor necrosis factor inhibitors as well as the interleukin 12/23 inhibitor ustekinumab, said Dr. Leonardi of the dermatology department at St. Louis University.

It seems likely that the next iteration of the AAD psoriasis guidelines will firmly recommend universal pretreatment screening for hepatitis. That hand was tipped in a recent review article coauthored by Dr. Alan Menter, chair of the AAD psoriasis guidelines committee.

Dr. Menter and his coauthors endorsed universal screening for hepatitis B surface antigen and HBV core antigen prior to initiating anti-TNF therapy in psoriasis patients. And while the American College of Rheumatology guidelines say anti-TNF therapy is contraindicated in patients with chronic hepatitis B, Dr. Menter and his colleagues took issue. They argued that these important biologic therapies can be used safely for psoriasis, citing evidence that the risk of reactivation of hepatitis B can be greatly minimized or eliminated altogether by preemptive antiviral therapy (J. Am. Acad. Dermatol. 2012;67:1349-61).

They advocated preferential consideration of etanercept over the other TNF-inhibitors in light of evidence suggesting it renders HBV reactivation less likely. They further recommended monthly testing of serum transaminase levels for the first 6 months of therapy in patients with chronic HBV, quarterly testing thereafter, and referral to a hepatologist if liver enzyme levels climb above three times baseline.

A major impetus behind the increased attention being given to screening for hepatitis in patients prior to long-term immunosuppressive therapy was an influential paper published last year by investigators at the CDC, the American Association for the Study of Liver Diseases, and other institutions. The authors underscored the risk of HBV reactivation during such therapy, calling it a neglected danger that is poorly recognized in some professional medical groups’ treatment guidelines (Ann. Intern. Med. 2012;156:743-5).

The risk of HBV reactivation is substantial with anti-TNF therapy in patients who express surface antigen – in the 40% range in one review – but less than 5% in those who are core antibody–positive only.

The risk of hepatitis B reactivation during immunosuppressive therapy has gotten most of the recent attention because of the vast scope of HBV worldwide, with close to 400 million people being chronically infected. In his own busy, universally screened psoriasis practice, however, Dr. Leonardi said that uncovering chronic hepatitis C comes up far more commonly.

The medical board at the National Psoriasis Foundation has cautioned that standard interferon-alpha therapy for HCV seriously exacerbates psoriasis. The group recommends considering the full range of therapeutic options in treating psoriasis in HCV-positive patients. Topical therapies are called the best option for those with limited skin disease. Second-line therapies include UVB phototherapy, acitretin, etanercept, PUVA, and possibly the other TNF-antagonists, with cyclosporine and azathioprine held in reserve as the third line (J. Am. Acad. Dermatol. 2009;61:1044-55).

The recommendation is to monitor quantitative hepatitis C viral counts and liver enzymes during psoriasis therapy and refer to a hepatologist early should levels spike.

As yet, there are very few data on the impact of ustekinumab in patients who are HBV or HCV positive, and no meaningful conclusions as to risk are possible yet, Dr. Leonardi said.

He reported that he serves as a consultant to and recipient of research grants from all the major pharmaceutical companies having an interest in biologic therapies for psoriasis. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Routine screening for hepatitis B and C has become a must prior to initiation of chronic immunosuppressive therapy for psoriasis, Dr. Craig L. Leonardi said.

"Universal screening for hepatitis B and hepatitis C infection is not optional in 2013," he stressed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

That said, professional society guidelines are at odds and in flux on this issue. The American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Centers for Disease Control and Prevention all recommend routine screening for hepatitis B surface antigen and hepatitis B core antibody prior to initiation of immunosuppressive therapy. The CDC also recommends universal pretreatment testing for antibody to hepatitis B surface antibody.

In contrast, the American College of Rheumatology recommends HBV screening only in high-risk patients and those treated with specific drugs (Arthritis Rheum. 2008;59:762-84).

For now, the American Academy of Dermatology guidelines take a middle-of-the-road position, which Dr. Leonardi said he finds unconvincing. The current guidelines recommend hepatitis B screening in the appropriate setting (J. Am. Acad. Dermatol. 2008;58:826-50).

"Well, the appropriate setting is when you’re going to use immunosuppressive agents," he asserted. "So I think we all need to start ordering these tests and be on the lookout for the problem. Prophylactic antiviral therapy may be more than the average dermatologist wants to take on. Nonetheless, you want to do the testing and then refer affected patients to an experienced hepatology center."

Chronic immunosuppressive therapy for psoriasis encompasses all the biologics agents – the tumor necrosis factor inhibitors as well as the interleukin 12/23 inhibitor ustekinumab, said Dr. Leonardi of the dermatology department at St. Louis University.

It seems likely that the next iteration of the AAD psoriasis guidelines will firmly recommend universal pretreatment screening for hepatitis. That hand was tipped in a recent review article coauthored by Dr. Alan Menter, chair of the AAD psoriasis guidelines committee.

Dr. Menter and his coauthors endorsed universal screening for hepatitis B surface antigen and HBV core antigen prior to initiating anti-TNF therapy in psoriasis patients. And while the American College of Rheumatology guidelines say anti-TNF therapy is contraindicated in patients with chronic hepatitis B, Dr. Menter and his colleagues took issue. They argued that these important biologic therapies can be used safely for psoriasis, citing evidence that the risk of reactivation of hepatitis B can be greatly minimized or eliminated altogether by preemptive antiviral therapy (J. Am. Acad. Dermatol. 2012;67:1349-61).

They advocated preferential consideration of etanercept over the other TNF-inhibitors in light of evidence suggesting it renders HBV reactivation less likely. They further recommended monthly testing of serum transaminase levels for the first 6 months of therapy in patients with chronic HBV, quarterly testing thereafter, and referral to a hepatologist if liver enzyme levels climb above three times baseline.

A major impetus behind the increased attention being given to screening for hepatitis in patients prior to long-term immunosuppressive therapy was an influential paper published last year by investigators at the CDC, the American Association for the Study of Liver Diseases, and other institutions. The authors underscored the risk of HBV reactivation during such therapy, calling it a neglected danger that is poorly recognized in some professional medical groups’ treatment guidelines (Ann. Intern. Med. 2012;156:743-5).

The risk of HBV reactivation is substantial with anti-TNF therapy in patients who express surface antigen – in the 40% range in one review – but less than 5% in those who are core antibody–positive only.

The risk of hepatitis B reactivation during immunosuppressive therapy has gotten most of the recent attention because of the vast scope of HBV worldwide, with close to 400 million people being chronically infected. In his own busy, universally screened psoriasis practice, however, Dr. Leonardi said that uncovering chronic hepatitis C comes up far more commonly.

The medical board at the National Psoriasis Foundation has cautioned that standard interferon-alpha therapy for HCV seriously exacerbates psoriasis. The group recommends considering the full range of therapeutic options in treating psoriasis in HCV-positive patients. Topical therapies are called the best option for those with limited skin disease. Second-line therapies include UVB phototherapy, acitretin, etanercept, PUVA, and possibly the other TNF-antagonists, with cyclosporine and azathioprine held in reserve as the third line (J. Am. Acad. Dermatol. 2009;61:1044-55).

The recommendation is to monitor quantitative hepatitis C viral counts and liver enzymes during psoriasis therapy and refer to a hepatologist early should levels spike.

As yet, there are very few data on the impact of ustekinumab in patients who are HBV or HCV positive, and no meaningful conclusions as to risk are possible yet, Dr. Leonardi said.

He reported that he serves as a consultant to and recipient of research grants from all the major pharmaceutical companies having an interest in biologic therapies for psoriasis. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

MAUI, HAWAII – Routine screening for hepatitis B and C has become a must prior to initiation of chronic immunosuppressive therapy for psoriasis, Dr. Craig L. Leonardi said.

"Universal screening for hepatitis B and hepatitis C infection is not optional in 2013," he stressed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

That said, professional society guidelines are at odds and in flux on this issue. The American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Centers for Disease Control and Prevention all recommend routine screening for hepatitis B surface antigen and hepatitis B core antibody prior to initiation of immunosuppressive therapy. The CDC also recommends universal pretreatment testing for antibody to hepatitis B surface antibody.

In contrast, the American College of Rheumatology recommends HBV screening only in high-risk patients and those treated with specific drugs (Arthritis Rheum. 2008;59:762-84).

For now, the American Academy of Dermatology guidelines take a middle-of-the-road position, which Dr. Leonardi said he finds unconvincing. The current guidelines recommend hepatitis B screening in the appropriate setting (J. Am. Acad. Dermatol. 2008;58:826-50).

"Well, the appropriate setting is when you’re going to use immunosuppressive agents," he asserted. "So I think we all need to start ordering these tests and be on the lookout for the problem. Prophylactic antiviral therapy may be more than the average dermatologist wants to take on. Nonetheless, you want to do the testing and then refer affected patients to an experienced hepatology center."

Chronic immunosuppressive therapy for psoriasis encompasses all the biologics agents – the tumor necrosis factor inhibitors as well as the interleukin 12/23 inhibitor ustekinumab, said Dr. Leonardi of the dermatology department at St. Louis University.

It seems likely that the next iteration of the AAD psoriasis guidelines will firmly recommend universal pretreatment screening for hepatitis. That hand was tipped in a recent review article coauthored by Dr. Alan Menter, chair of the AAD psoriasis guidelines committee.

Dr. Menter and his coauthors endorsed universal screening for hepatitis B surface antigen and HBV core antigen prior to initiating anti-TNF therapy in psoriasis patients. And while the American College of Rheumatology guidelines say anti-TNF therapy is contraindicated in patients with chronic hepatitis B, Dr. Menter and his colleagues took issue. They argued that these important biologic therapies can be used safely for psoriasis, citing evidence that the risk of reactivation of hepatitis B can be greatly minimized or eliminated altogether by preemptive antiviral therapy (J. Am. Acad. Dermatol. 2012;67:1349-61).

They advocated preferential consideration of etanercept over the other TNF-inhibitors in light of evidence suggesting it renders HBV reactivation less likely. They further recommended monthly testing of serum transaminase levels for the first 6 months of therapy in patients with chronic HBV, quarterly testing thereafter, and referral to a hepatologist if liver enzyme levels climb above three times baseline.

A major impetus behind the increased attention being given to screening for hepatitis in patients prior to long-term immunosuppressive therapy was an influential paper published last year by investigators at the CDC, the American Association for the Study of Liver Diseases, and other institutions. The authors underscored the risk of HBV reactivation during such therapy, calling it a neglected danger that is poorly recognized in some professional medical groups’ treatment guidelines (Ann. Intern. Med. 2012;156:743-5).

The risk of HBV reactivation is substantial with anti-TNF therapy in patients who express surface antigen – in the 40% range in one review – but less than 5% in those who are core antibody–positive only.

The risk of hepatitis B reactivation during immunosuppressive therapy has gotten most of the recent attention because of the vast scope of HBV worldwide, with close to 400 million people being chronically infected. In his own busy, universally screened psoriasis practice, however, Dr. Leonardi said that uncovering chronic hepatitis C comes up far more commonly.

The medical board at the National Psoriasis Foundation has cautioned that standard interferon-alpha therapy for HCV seriously exacerbates psoriasis. The group recommends considering the full range of therapeutic options in treating psoriasis in HCV-positive patients. Topical therapies are called the best option for those with limited skin disease. Second-line therapies include UVB phototherapy, acitretin, etanercept, PUVA, and possibly the other TNF-antagonists, with cyclosporine and azathioprine held in reserve as the third line (J. Am. Acad. Dermatol. 2009;61:1044-55).

The recommendation is to monitor quantitative hepatitis C viral counts and liver enzymes during psoriasis therapy and refer to a hepatologist early should levels spike.

As yet, there are very few data on the impact of ustekinumab in patients who are HBV or HCV positive, and no meaningful conclusions as to risk are possible yet, Dr. Leonardi said.

He reported that he serves as a consultant to and recipient of research grants from all the major pharmaceutical companies having an interest in biologic therapies for psoriasis. SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

ORLANDO – Although current guidelines do not recommend the use of systemic steroids for treatment of psoriasis, dermatologists still prescribe them, according to data presented at the Orlando Dermatology Aesthetic and Clinical Conference.

Researchers at Wake Forest University in Winston-Salem, N.C., analyzed a national database and found that U.S. dermatologists wrote more than 90% of the nearly 660,000 systemic steroid prescriptions for psoriasis over an 11-year period.

The authors concluded that the usefulness of systemic steroids for psoriasis should be reexamined in light of their findings.

"This is an issue that has been buried for a while," said Amir Al-Dabagh, the study’s first author and a fourth-year medical student at Wake Forest University. "Everyone knows it’s there, but it’s not discussed," he said.

Systemic steroids are not recommended for treatment of psoriasis because of evidence that discontinuing the drugs could lead to a rebound flair, sometimes beyond the baseline.

In addition, there are no data that systemic steroids are safe and effective in long-term treatment of psoriasis, said Dr. Joel Gelfand, one of the authors of the American Academy of Dermatology’s psoriasis guidelines, who was not involved in the analysis.

But, in reality, physicians do prescribe systemic steroids from time to time, especially when the patients are acutely flaring, said Dr. Gelfand, of the University of Pennsylvania in Philadelphia. "The general consensus is that it’s not a good thing to do. But sometimes the practitioners are stuck, and there are no other options for patients," he said in an interview.

Also, he added, not everyone follows the guidelines.

To analyze the prescription of steroids, Mr. Al-Dabagh and his colleagues used data from the National Ambulatory Medical Care Survey (NAMCS) from 1989 to 2010. In addition to showing that 90% of the systemic steroid prescriptions for psoriasis were written by dermatologists, the results indicated that three of the nine systemic therapies prescribed were steroids. Prednisone was ranked fourth among the nine therapies, and ranked first among the three systemic steroids, followed by methylprednisolone and dexamethasone.

In addition, no significant change was observed in the use of systemic steroids over the 11-year study period.

The poster’s findings are similar to the results of a 2011 German study that showed that systemic steroids are often used to treat psoriasis, although this treatment is not recommended in the European guidelines. The majority of prescribers in the German study were general practitioners and internists in Europe (J. Dtsch. Dermatol. Ges. 2011;9:833-8).

"If the dogma were true that systemic corticosteroids are frequently associated with severe exacerbations of the disease, then with the wide use of corticosteroids both for psoriasis and for comorbidities of psoriasis, we would expect that large numbers of patients would be seen for major problems such as precipitation, worsening, or rebound of their psoriasis. However, this has not been reported in the literature," Mr. Al-Dabagh and his colleagues wrote.

Academic dermatologists only see patients who aren’t cured by the physicians who prescribe the medications, which results in a selection bias where only the worst cases are seen in academia, the researchers noted. "This phenomenon may explain how steroids may be effective even though ‘everybody knows they don’t work,’ " they added.

Dr. Steven R. Feldman, senior author of the analysis and professor of dermatology at Wake Forest University, said that he and colleagues agreed with the current guidelines, but clinical trials of steroids for psoriasis would be helpful. "Avoiding systemic steroids in psoriasis is dogma, but is not supported by a strong scientific rationale," he said.

"There are long-term side effects from chronic use of systemic steroids, but we can say that about nearly all the treatments we use. The concerns about rebound from short-term use for psoriasis may be overblown as well," he added.

The debate on the use of systemic steroids for treatment of psoriasis is ongoing. Authors of a 2012 European study tried to parse out fact from fiction regarding the treatment and the condition. "There’s a remarkable lack of literature addressing adverse effects such as rebound, pustular, or erythrodermic flares or even new occurrence of psoriasis in patients with a negative disease history," the authors wrote. "A re-evaluation of the treatment of psoriasis and/or psoriatic arthritis with systemic steroids is necessary," the authors concluded (J. Eur. Acad. Dermatol. Venereol. 2012 Jul 25 [doi: 10.1111/j.1468-3083.2012.04656.x]).

More research is needed in the form of double-blind, controlled trials, Mr. Al-Dabagh said.

Mr. Al-Dabagh had no disclosures. Dr. Gelfand had no disclosures. Dr. Feldman said he had relationships with several pharmaceutical companies, but none produced systemic steroids.

ORLANDO – Although current guidelines do not recommend the use of systemic steroids for treatment of psoriasis, dermatologists still prescribe them, according to data presented at the Orlando Dermatology Aesthetic and Clinical Conference.

Researchers at Wake Forest University in Winston-Salem, N.C., analyzed a national database and found that U.S. dermatologists wrote more than 90% of the nearly 660,000 systemic steroid prescriptions for psoriasis over an 11-year period.

The authors concluded that the usefulness of systemic steroids for psoriasis should be reexamined in light of their findings.

"This is an issue that has been buried for a while," said Amir Al-Dabagh, the study’s first author and a fourth-year medical student at Wake Forest University. "Everyone knows it’s there, but it’s not discussed," he said.

Systemic steroids are not recommended for treatment of psoriasis because of evidence that discontinuing the drugs could lead to a rebound flair, sometimes beyond the baseline.

In addition, there are no data that systemic steroids are safe and effective in long-term treatment of psoriasis, said Dr. Joel Gelfand, one of the authors of the American Academy of Dermatology’s psoriasis guidelines, who was not involved in the analysis.

But, in reality, physicians do prescribe systemic steroids from time to time, especially when the patients are acutely flaring, said Dr. Gelfand, of the University of Pennsylvania in Philadelphia. "The general consensus is that it’s not a good thing to do. But sometimes the practitioners are stuck, and there are no other options for patients," he said in an interview.

Also, he added, not everyone follows the guidelines.

To analyze the prescription of steroids, Mr. Al-Dabagh and his colleagues used data from the National Ambulatory Medical Care Survey (NAMCS) from 1989 to 2010. In addition to showing that 90% of the systemic steroid prescriptions for psoriasis were written by dermatologists, the results indicated that three of the nine systemic therapies prescribed were steroids. Prednisone was ranked fourth among the nine therapies, and ranked first among the three systemic steroids, followed by methylprednisolone and dexamethasone.

In addition, no significant change was observed in the use of systemic steroids over the 11-year study period.

The poster’s findings are similar to the results of a 2011 German study that showed that systemic steroids are often used to treat psoriasis, although this treatment is not recommended in the European guidelines. The majority of prescribers in the German study were general practitioners and internists in Europe (J. Dtsch. Dermatol. Ges. 2011;9:833-8).

"If the dogma were true that systemic corticosteroids are frequently associated with severe exacerbations of the disease, then with the wide use of corticosteroids both for psoriasis and for comorbidities of psoriasis, we would expect that large numbers of patients would be seen for major problems such as precipitation, worsening, or rebound of their psoriasis. However, this has not been reported in the literature," Mr. Al-Dabagh and his colleagues wrote.

Academic dermatologists only see patients who aren’t cured by the physicians who prescribe the medications, which results in a selection bias where only the worst cases are seen in academia, the researchers noted. "This phenomenon may explain how steroids may be effective even though ‘everybody knows they don’t work,’ " they added.

Dr. Steven R. Feldman, senior author of the analysis and professor of dermatology at Wake Forest University, said that he and colleagues agreed with the current guidelines, but clinical trials of steroids for psoriasis would be helpful. "Avoiding systemic steroids in psoriasis is dogma, but is not supported by a strong scientific rationale," he said.

"There are long-term side effects from chronic use of systemic steroids, but we can say that about nearly all the treatments we use. The concerns about rebound from short-term use for psoriasis may be overblown as well," he added.

The debate on the use of systemic steroids for treatment of psoriasis is ongoing. Authors of a 2012 European study tried to parse out fact from fiction regarding the treatment and the condition. "There’s a remarkable lack of literature addressing adverse effects such as rebound, pustular, or erythrodermic flares or even new occurrence of psoriasis in patients with a negative disease history," the authors wrote. "A re-evaluation of the treatment of psoriasis and/or psoriatic arthritis with systemic steroids is necessary," the authors concluded (J. Eur. Acad. Dermatol. Venereol. 2012 Jul 25 [doi: 10.1111/j.1468-3083.2012.04656.x]).

More research is needed in the form of double-blind, controlled trials, Mr. Al-Dabagh said.

Mr. Al-Dabagh had no disclosures. Dr. Gelfand had no disclosures. Dr. Feldman said he had relationships with several pharmaceutical companies, but none produced systemic steroids.

ORLANDO – Although current guidelines do not recommend the use of systemic steroids for treatment of psoriasis, dermatologists still prescribe them, according to data presented at the Orlando Dermatology Aesthetic and Clinical Conference.

Researchers at Wake Forest University in Winston-Salem, N.C., analyzed a national database and found that U.S. dermatologists wrote more than 90% of the nearly 660,000 systemic steroid prescriptions for psoriasis over an 11-year period.

The authors concluded that the usefulness of systemic steroids for psoriasis should be reexamined in light of their findings.

"This is an issue that has been buried for a while," said Amir Al-Dabagh, the study’s first author and a fourth-year medical student at Wake Forest University. "Everyone knows it’s there, but it’s not discussed," he said.

Systemic steroids are not recommended for treatment of psoriasis because of evidence that discontinuing the drugs could lead to a rebound flair, sometimes beyond the baseline.

In addition, there are no data that systemic steroids are safe and effective in long-term treatment of psoriasis, said Dr. Joel Gelfand, one of the authors of the American Academy of Dermatology’s psoriasis guidelines, who was not involved in the analysis.

But, in reality, physicians do prescribe systemic steroids from time to time, especially when the patients are acutely flaring, said Dr. Gelfand, of the University of Pennsylvania in Philadelphia. "The general consensus is that it’s not a good thing to do. But sometimes the practitioners are stuck, and there are no other options for patients," he said in an interview.

Also, he added, not everyone follows the guidelines.

To analyze the prescription of steroids, Mr. Al-Dabagh and his colleagues used data from the National Ambulatory Medical Care Survey (NAMCS) from 1989 to 2010. In addition to showing that 90% of the systemic steroid prescriptions for psoriasis were written by dermatologists, the results indicated that three of the nine systemic therapies prescribed were steroids. Prednisone was ranked fourth among the nine therapies, and ranked first among the three systemic steroids, followed by methylprednisolone and dexamethasone.

In addition, no significant change was observed in the use of systemic steroids over the 11-year study period.

The poster’s findings are similar to the results of a 2011 German study that showed that systemic steroids are often used to treat psoriasis, although this treatment is not recommended in the European guidelines. The majority of prescribers in the German study were general practitioners and internists in Europe (J. Dtsch. Dermatol. Ges. 2011;9:833-8).

"If the dogma were true that systemic corticosteroids are frequently associated with severe exacerbations of the disease, then with the wide use of corticosteroids both for psoriasis and for comorbidities of psoriasis, we would expect that large numbers of patients would be seen for major problems such as precipitation, worsening, or rebound of their psoriasis. However, this has not been reported in the literature," Mr. Al-Dabagh and his colleagues wrote.

Academic dermatologists only see patients who aren’t cured by the physicians who prescribe the medications, which results in a selection bias where only the worst cases are seen in academia, the researchers noted. "This phenomenon may explain how steroids may be effective even though ‘everybody knows they don’t work,’ " they added.

Dr. Steven R. Feldman, senior author of the analysis and professor of dermatology at Wake Forest University, said that he and colleagues agreed with the current guidelines, but clinical trials of steroids for psoriasis would be helpful. "Avoiding systemic steroids in psoriasis is dogma, but is not supported by a strong scientific rationale," he said.

"There are long-term side effects from chronic use of systemic steroids, but we can say that about nearly all the treatments we use. The concerns about rebound from short-term use for psoriasis may be overblown as well," he added.

The debate on the use of systemic steroids for treatment of psoriasis is ongoing. Authors of a 2012 European study tried to parse out fact from fiction regarding the treatment and the condition. "There’s a remarkable lack of literature addressing adverse effects such as rebound, pustular, or erythrodermic flares or even new occurrence of psoriasis in patients with a negative disease history," the authors wrote. "A re-evaluation of the treatment of psoriasis and/or psoriatic arthritis with systemic steroids is necessary," the authors concluded (J. Eur. Acad. Dermatol. Venereol. 2012 Jul 25 [doi: 10.1111/j.1468-3083.2012.04656.x]).

More research is needed in the form of double-blind, controlled trials, Mr. Al-Dabagh said.

Mr. Al-Dabagh had no disclosures. Dr. Gelfand had no disclosures. Dr. Feldman said he had relationships with several pharmaceutical companies, but none produced systemic steroids.