Psoriasis

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

BERLIN – Obese patients with psoriatic arthritis demonstrate a worse response when starting anti–tumor necrosis factor therapy than do normal weight patients, but achievement of minimal disease activity can be improved by weight loss, based on two studies by Dr. Giovanni Di Minno, lead investigator on both.

The first study investigated the influence of obesity and the second, the influence of weight loss on response to starting anti–tumor necrosis factor (TNF) therapy.

The study on the effect of obesity on response to anti-TNF therapy in psoriatic arthritis (PsA) involved 135 psoriatic arthritis patients with a body mass index (BMI) over 30 kg/m²and 135 normal weight controls. Dr. Di Minno and his coinvestigators found that the two groups did not differ significantly in terms of disease activity and vascular risk factors including swollen and tender joint counts, levels of C-reactive protein, erythrocyte sedimentation rates, and psoriasis area severity index scores. They found that patients with a BMI over 30 had a higher prevalence of hypercholesterolemia and hypertriglyceridemia.

"Controlling weight is very important for these patients in the long term."

Dr. Di Minno and his associates in the department of clinical and experimental medicine, Federico II University, Naples, Italy, found that at 12 months’ follow-up, 98 of the 270 patients (36.3%) had achieved minimal disease activity (MDA). The prevalence of obesity was higher in those not achieving MDA than in those achieving it (64% vs. 25.5%, P less than .001).

"A BMI of over 30 was shown to be a strong predictor [of not achieving MDA] with a hazard ratio of 4.90 (95%CI: 3.04-7.87; P less than .001)," according to Cox regression analysis findings, reported Dr. Di Minno.

At 24 months, 17.3% of those who achieved MDA a year earlier relapsed, and 82.7% maintained their MDA. "A BMI greater than 30 was associated with a higher risk of disease relapse, with a hazard ratio of 2.04 [95% CI: 1.02-3.61; P = .014]," he said at the annual European Congress of Rheumatology.

Dr. Di Minno also noted that there was no difference found between the three anti-TNF blockers (infliximab, etanercept, and adalimumab) used in the study.

Session moderator Dr. Laura Coates said that the study was valuable because patients with PsA were prone to being overweight, and there was an established link between excess weight, metabolic syndrome, and psoriasis. "Until this study, there were no data to support the concept that weight loss could alter people’s outcome in terms of their arthritis response.

"This provides evidence of an immediate improvement to people’s health with weight loss, in terms of a better response to the anti-TNF therapies," said Dr. Coates of the division of rheumatic and musculoskeletal disease at Chapel Allerton Hospital in Leeds, England.

Furthermore, Dr. Coates noted that there was also a known association between psoriasis/PsA and cardiovascular morbidity related to the metabolic syndrome. "Controlling weight is very important for these patients in the long term as well," she said.

Introducing his second study, which investigated the effect of weight loss in obese patients, Dr Di Minno noted that prior studies had shown that restricting calorie intake reduced obesity-related inflammation.

The study specifically investigated the impact of changes in body weight on the achievement of MDA in PsA patients starting treatment on anti-TNF therapy.

A total of 126 obese (BMI greater than 30) patients with active PsA, who had not responded to traditional disease-modifying antirheumaic drugs were randomized to either a diet of 1,300 calories per day (n = 63), or an unrestricted diet (n = 63), with the advice to eat more vegetables, fish, and fresh fruits and no more than 2 tablespoons of olive oil per day. All patients were encouraged to exercise five times a week, and all started on anti-TNF therapy immediately.

"The intervention diet was the traditional Mediterranean diet rich in fibers, with a careful balance of sugar, proteins, and lipids, similar to the diet used by diabetics," explained Dr. Di Minno. The Mediterranean diet has been shown to lessen inflammation because it is rich in mono- and polyunsaturated fatty acids, antioxidants, dietary fiber, and phytochemicals.

At the 6-month follow-up, the researchers found a 5%-10% weight loss was achieved by 47.6% of patients on the hypocaloric diet versus 28.6% on the unrestricted diet. Only 41.3% of patients on the hypocaloric diet lost more than 10% of their body weight.

Furthermore, patients on the hypocaloric diet had more significant reductions in triglycerides and cholesterol compared with those on the unrestricted diet (29.1% vs. 10% for triglycerides. and 23.7% vs. 8.1% for cholesterol, for hypocaloric and unrestricted diets, respectively).

"To our surprise we found that the Mediterranean diet was not much better than the other diet in terms of MDA achievement [42.9% on the hypocaloric diet vs. 34.9% on the free diet; P = .465]," reported Dr. Di Minno.

MDA was achieved more frequently by patients who achieved a greater than 5% weight loss compared with those who did not [50% vs. 23.1%]. Furthermore, as weight loss increased so did the achievement of MDA, with 16.7%, 42.9%, and 59.5% MDA achievement for a weight loss of less than 5%, 5%-10%, and more than 10%, respectively.

The data strongly support the need for the control of body weight and cardiometabolic parameters in PsA subjects starting anti-TNF treatment, Dr. Di Minno said. "This may result in a better achievement of minimal disease activity in these patients."

Dr. Di Minno and Dr. Coates reported having no relevant financial conflicts.

Psoriatic arthritis patients who are taking a tumor necrosis factor inhibitor for the first time do about the same with or without the addition of methotrexate, Dr. Karen M. Fagerli said at the annual European Congress of Rheumatology.

Patients who received concomitant methotrexate, however, were more likely to still be taking that therapy after 3 years than were patients on anti-TNF monotherapy.

Dr. Fagerli of the Diakonhjemmet Hospital, Oslo, and her colleagues presented new data on the impact of concomitant medication with methotrexate for psoriatic arthritis patients who are taking a TNF inhibitor for the first time. Although comedication with methotrexate is known to be helpful in rheumatoid arthritis and ineffective in ankylosing spondylitis, its value has been unclear when comes to psoriatic arthritis.

"The jury is very much still out on this," Dr. Fagerli said in an interview.

The new data indicate that the combination of methotrexate and a TNF inhibitor doesn’t have the same synergistic effect in psoriatic arthritis as it does in rheumatoid arthritis, but the fact that patients on combination therapy had superior drug survival indicates that there is a role for methotrexate with a TNF inhibitor, she said.

"We saw similar responses in patients with or without concomitant methotrexate. However, there were improved 3-year drug survival rates seen with concomitant methotrexate. This was most prominent in patients on infliximab, but there was no clear trend in patients receiving etanercept," she reported.

Figuring out exactly what that role is and which patients can most benefit from this combination of treatments will require more research. Examining the treatment effect in psoriatic arthritis is a growing area of study, Dr. Fagerli said, as more researchers look for effects specifically in that condition, rather than adopting practice from other diseases.

"I think this is really an emerging issue," Dr. Fagerli said.

In this study, the researchers analyzed data from the NOR-DMARD register, a repository of data on adult patients with inflammatory arthropathies who are starting a new DMARD (disease-modifying antirheumatic drug) treatment. The register, which began in 2000, includes patients consecutively from across five rheumatology departments in Norway. The current analysis included 370 psoriatic arthritis patients who were being treated with their first TNF inhibitor. The patients were receiving either combined treatment with methotrexate or were not receiving a concomitant DMARD.

At 3 months, there was very little difference in either the state of disease or the change from baseline between the two groups. The researchers considered responses on the patient and physician global assessments and the Modified Health Assessment Questionnaire and SF-6D health status instruments. However, there was an improved 3-year drug survival in the group receiving combination treatment.

Dr. Fagerli reported that she has received speakers honoraria from Abbott, MSD, Pfizer, and Roche.

Psoriatic arthritis patients who are taking a tumor necrosis factor inhibitor for the first time do about the same with or without the addition of methotrexate, Dr. Karen M. Fagerli said at the annual European Congress of Rheumatology.

Patients who received concomitant methotrexate, however, were more likely to still be taking that therapy after 3 years than were patients on anti-TNF monotherapy.

Dr. Fagerli of the Diakonhjemmet Hospital, Oslo, and her colleagues presented new data on the impact of concomitant medication with methotrexate for psoriatic arthritis patients who are taking a TNF inhibitor for the first time. Although comedication with methotrexate is known to be helpful in rheumatoid arthritis and ineffective in ankylosing spondylitis, its value has been unclear when comes to psoriatic arthritis.

"The jury is very much still out on this," Dr. Fagerli said in an interview.

The new data indicate that the combination of methotrexate and a TNF inhibitor doesn’t have the same synergistic effect in psoriatic arthritis as it does in rheumatoid arthritis, but the fact that patients on combination therapy had superior drug survival indicates that there is a role for methotrexate with a TNF inhibitor, she said.

"We saw similar responses in patients with or without concomitant methotrexate. However, there were improved 3-year drug survival rates seen with concomitant methotrexate. This was most prominent in patients on infliximab, but there was no clear trend in patients receiving etanercept," she reported.

Figuring out exactly what that role is and which patients can most benefit from this combination of treatments will require more research. Examining the treatment effect in psoriatic arthritis is a growing area of study, Dr. Fagerli said, as more researchers look for effects specifically in that condition, rather than adopting practice from other diseases.

"I think this is really an emerging issue," Dr. Fagerli said.

In this study, the researchers analyzed data from the NOR-DMARD register, a repository of data on adult patients with inflammatory arthropathies who are starting a new DMARD (disease-modifying antirheumatic drug) treatment. The register, which began in 2000, includes patients consecutively from across five rheumatology departments in Norway. The current analysis included 370 psoriatic arthritis patients who were being treated with their first TNF inhibitor. The patients were receiving either combined treatment with methotrexate or were not receiving a concomitant DMARD.

At 3 months, there was very little difference in either the state of disease or the change from baseline between the two groups. The researchers considered responses on the patient and physician global assessments and the Modified Health Assessment Questionnaire and SF-6D health status instruments. However, there was an improved 3-year drug survival in the group receiving combination treatment.

Dr. Fagerli reported that she has received speakers honoraria from Abbott, MSD, Pfizer, and Roche.

Psoriatic arthritis patients who are taking a tumor necrosis factor inhibitor for the first time do about the same with or without the addition of methotrexate, Dr. Karen M. Fagerli said at the annual European Congress of Rheumatology.

Patients who received concomitant methotrexate, however, were more likely to still be taking that therapy after 3 years than were patients on anti-TNF monotherapy.

Dr. Fagerli of the Diakonhjemmet Hospital, Oslo, and her colleagues presented new data on the impact of concomitant medication with methotrexate for psoriatic arthritis patients who are taking a TNF inhibitor for the first time. Although comedication with methotrexate is known to be helpful in rheumatoid arthritis and ineffective in ankylosing spondylitis, its value has been unclear when comes to psoriatic arthritis.

"The jury is very much still out on this," Dr. Fagerli said in an interview.

The new data indicate that the combination of methotrexate and a TNF inhibitor doesn’t have the same synergistic effect in psoriatic arthritis as it does in rheumatoid arthritis, but the fact that patients on combination therapy had superior drug survival indicates that there is a role for methotrexate with a TNF inhibitor, she said.

"We saw similar responses in patients with or without concomitant methotrexate. However, there were improved 3-year drug survival rates seen with concomitant methotrexate. This was most prominent in patients on infliximab, but there was no clear trend in patients receiving etanercept," she reported.

Figuring out exactly what that role is and which patients can most benefit from this combination of treatments will require more research. Examining the treatment effect in psoriatic arthritis is a growing area of study, Dr. Fagerli said, as more researchers look for effects specifically in that condition, rather than adopting practice from other diseases.

"I think this is really an emerging issue," Dr. Fagerli said.

In this study, the researchers analyzed data from the NOR-DMARD register, a repository of data on adult patients with inflammatory arthropathies who are starting a new DMARD (disease-modifying antirheumatic drug) treatment. The register, which began in 2000, includes patients consecutively from across five rheumatology departments in Norway. The current analysis included 370 psoriatic arthritis patients who were being treated with their first TNF inhibitor. The patients were receiving either combined treatment with methotrexate or were not receiving a concomitant DMARD.

At 3 months, there was very little difference in either the state of disease or the change from baseline between the two groups. The researchers considered responses on the patient and physician global assessments and the Modified Health Assessment Questionnaire and SF-6D health status instruments. However, there was an improved 3-year drug survival in the group receiving combination treatment.

Dr. Fagerli reported that she has received speakers honoraria from Abbott, MSD, Pfizer, and Roche.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

Ustekinumab at 45-mg and 90-mg doses significantly improved arthritis symptoms, physical function, and inflammation in adults with psoriatic arthritis, compared with placebo, after 24 weeks of treatment, according to findings presented by Dr. Iain B. McInnes at the annual European Congress of Rheumatology.

These findings come from the PSUMMIT I study, a multicenter, randomized trial of 615 patients. Participants were patients whose psoriatic arthritis (PsA) remained persistent, despite treatment with NSAIDS or disease-modifying antirheumatic drugs (DMARDs). They were randomized to 45 mg of ustekinumab, 90 mg of ustekinumab, or a placebo. Patients who had been treated with anti–tumor necrosis factor (anti-TNF) agents were excluded from the study.

After 24 weeks, approximately half of the patients in the 45 mg–dose (42%) and 90 mg–dose (50%) groups achieved an ACR 20 response (that is, a 20% improvement based on certain parameters specified by the American College of Rheumatology); the percentages for both groups were significantly greater than that of the placebo group (23%).

"These findings are in line with our expectations from the original phase II trial published a short number of years ago and with the success already enjoyed in using this medicine in treating the skin component of the psoriasis/psoriatic arthritis spectrum," said Dr. McInnes, director of the Institute for Infection, Inflammation, and Immunity at the University of Glascow (Scotland). The findings are also gratifying, he added. "There has been some evidence elsewhere to suggest that the cytokines that are targeted by ustekinumab might be of importance in psoriasis and psoriatic arthritis pathogenesis – these clinical data are compatible with those ideas," he noted.

Significantly more patients in both ustekinumab groups achieved ACR 50 and ACR 70 responses, compared with the placebo patients. In addition, ustekinumab patients had clinically meaningful changes from baseline Health Assessment Questionnaire Disability Index scores (defined as a change greater than or equal to 0.3), compared with placebo patients. Approximately twice as many patients in the two treatment groups demonstrated this change, compared with the placebo patients (48% vs. 28%, respectively).

The median change in enthesitis scores were 43% in the 45-mg ustekinumab group and 50% in the 90-mg ustekinumab group, compared with no change in the placebo group.

So far, no substantial differences in adverse events between the treatment and placebo groups have emerged, Dr. McInnes said in an interview. However, "this is a small trial – in comparison to the larger phase III and postmarketing datasets for this agent in the psoriasis field – and as such we need to be conservative in our interpretation of adverse events," he emphasized. "Continued vigilance will be the key here, and follow-up is ongoing," he said.

If the findings are confirmed in other studies, "we may be able to offer this agent to provide a new mode of action for the treatment of psoriatic arthritis, a disease for which we currently have too few options available," said Dr. McInnes. However, "it is too early to determine at which stage in the patient journey such use would be optimally employed," he said.

"It seems self-evident that use of ustekinumab would be after conventional drugs have been tried, and then, most likely it would be used after a TNF inhibitor because that has been the order of discovery. This reflects the RA treatment paradigm.

"But this might not be the best course; in fact, we might get similar results with different modes of action. So without head-to-head data we would make our decision based on the extent of safety data available. There is considerable safety evidence for ustekinumab in the skin literature; however, right now there is a challenge to work out where this drug will be used if it is marketed" said Dr. McInnes.

Approximately half of the patients were using methotrexate at baseline, but this did not impact the effect of ustekinumab vs. placebo.

Dr. McInnes reported financial support from Janssen Research and Development.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

RALEIGH, N.C. – Ustekinumab proved effective for the clearance of palmoplantar psoriasis in an open-label pilot study, but only at the higher 90-mg dose reserved under current labeling for psoriasis patients weighing at least 100 kg.

"Higher or more frequent dosing may be required to achieve clinical clearance in patients with palmoplantar psoriasis compared to current recommendations for plaque-type psoriasis," said Dr. Shiu-Chung Au of Tufts Medical Center, Boston.

Photos courtesy Dr. David J. Goldberg

Dr. Au presented an open-label, 24-week study of 20 patients with moderate to severe palmoplantar psoriasis that was refractory to topical corticosteroids. Dosing of ustekinumab (Stelara) was as for plaque-type psoriasis: The 11 patients weighing less than 100 kg received 45 mg subcutaneously at weeks 0, 4, and 16, whereas the 9 patients weighing 100 kg or more received 90 mg on the same schedule.

The primary study end point was a Palm-Sole PGA (Physician’s Global Assessment) score of 0 or 1 at week 16. The average baseline score on this 0-5 measure of induration, erythema, and scaling was 4. The primary end point was achieved in 1 of 11 patients on the 45-mg dose, compared with 6 of 9 on the 90-mg dose (J. Dermatolog. Treat. 2012 May 8. [Epub ahead of print]). Of 20 patients, 12 improved at least 2 points on the Palm-Sole PGA at week 16.

In addition, significant improvements were documented with respect to the secondary end points for pain and quality of life. The mean pain score on a 100-point visual analog scale improved from 51 at week 0 to 29 at week 16, and held steady with a score of 30 at 24 weeks. Moreover, the mean score on the Dermatology Life Quality Index improved from 13.9 at baseline to 6.05 at week 16 and to 6.18 at week 24.

Ustekinumab was well tolerated with no serious adverse events.

Palmoplantar psoriasis is an uncommon variant of psoriasis that constitutes a therapeutic challenge, noted Dr. Au. It can be disfiguring and disabling, even though affected patients don’t necessarily have a large area of body surface involvement. The condition is characterized by fissures and sterile inflammatory pustules, in addition to classic well-demarcated psoriasis plaques. Affected patients experience considerable skin pain, often accompanied by a burning sensation. Some patients are unable to walk.

Clinically, palmoplantar psoriasis can look like other diseases, including palmoplantar pustulosis, dyshidrotic eczema, tinea pedis, and contact dermatitis, he explained. To help eliminate other possible diagnoses in the differential diagnosis, participants in the ustekinumab study had to have at least one classic psoriasis plaque somewhere other than the palms and soles.

Current treatment of palmoplantar psoriasis has been unsatisfactory, noted Dr. Au. No standard therapy is recognized, which was the impetus for studying ustekinumab. Future studies will look at employing the 90-mg dose in patients who weigh less than 100 kg and/or administering the 45-mg dose more frequently than the current standard every 3 months, he added.

In response to an audience question, he noted that responsiveness to the 90-mg dose was not weight related. The average weight in the high-dose group was 250 pounds, and the three nonresponders weighed in similarly to the six responders.

This investigator-initiated ustekinumab study was funded by a grant from Janssen Pharmaceuticals. Dr. Au reported having no financial conflicts. Senior investigator Dr. Alice B. Gottlieb reported having numerous industry relationships.

RALEIGH, N.C. – Ustekinumab proved effective for the clearance of palmoplantar psoriasis in an open-label pilot study, but only at the higher 90-mg dose reserved under current labeling for psoriasis patients weighing at least 100 kg.

"Higher or more frequent dosing may be required to achieve clinical clearance in patients with palmoplantar psoriasis compared to current recommendations for plaque-type psoriasis," said Dr. Shiu-Chung Au of Tufts Medical Center, Boston.

Photos courtesy Dr. David J. Goldberg

Dr. Au presented an open-label, 24-week study of 20 patients with moderate to severe palmoplantar psoriasis that was refractory to topical corticosteroids. Dosing of ustekinumab (Stelara) was as for plaque-type psoriasis: The 11 patients weighing less than 100 kg received 45 mg subcutaneously at weeks 0, 4, and 16, whereas the 9 patients weighing 100 kg or more received 90 mg on the same schedule.

The primary study end point was a Palm-Sole PGA (Physician’s Global Assessment) score of 0 or 1 at week 16. The average baseline score on this 0-5 measure of induration, erythema, and scaling was 4. The primary end point was achieved in 1 of 11 patients on the 45-mg dose, compared with 6 of 9 on the 90-mg dose (J. Dermatolog. Treat. 2012 May 8. [Epub ahead of print]). Of 20 patients, 12 improved at least 2 points on the Palm-Sole PGA at week 16.

In addition, significant improvements were documented with respect to the secondary end points for pain and quality of life. The mean pain score on a 100-point visual analog scale improved from 51 at week 0 to 29 at week 16, and held steady with a score of 30 at 24 weeks. Moreover, the mean score on the Dermatology Life Quality Index improved from 13.9 at baseline to 6.05 at week 16 and to 6.18 at week 24.

Ustekinumab was well tolerated with no serious adverse events.

Palmoplantar psoriasis is an uncommon variant of psoriasis that constitutes a therapeutic challenge, noted Dr. Au. It can be disfiguring and disabling, even though affected patients don’t necessarily have a large area of body surface involvement. The condition is characterized by fissures and sterile inflammatory pustules, in addition to classic well-demarcated psoriasis plaques. Affected patients experience considerable skin pain, often accompanied by a burning sensation. Some patients are unable to walk.

Clinically, palmoplantar psoriasis can look like other diseases, including palmoplantar pustulosis, dyshidrotic eczema, tinea pedis, and contact dermatitis, he explained. To help eliminate other possible diagnoses in the differential diagnosis, participants in the ustekinumab study had to have at least one classic psoriasis plaque somewhere other than the palms and soles.

Current treatment of palmoplantar psoriasis has been unsatisfactory, noted Dr. Au. No standard therapy is recognized, which was the impetus for studying ustekinumab. Future studies will look at employing the 90-mg dose in patients who weigh less than 100 kg and/or administering the 45-mg dose more frequently than the current standard every 3 months, he added.

In response to an audience question, he noted that responsiveness to the 90-mg dose was not weight related. The average weight in the high-dose group was 250 pounds, and the three nonresponders weighed in similarly to the six responders.

This investigator-initiated ustekinumab study was funded by a grant from Janssen Pharmaceuticals. Dr. Au reported having no financial conflicts. Senior investigator Dr. Alice B. Gottlieb reported having numerous industry relationships.

RALEIGH, N.C. – Ustekinumab proved effective for the clearance of palmoplantar psoriasis in an open-label pilot study, but only at the higher 90-mg dose reserved under current labeling for psoriasis patients weighing at least 100 kg.

"Higher or more frequent dosing may be required to achieve clinical clearance in patients with palmoplantar psoriasis compared to current recommendations for plaque-type psoriasis," said Dr. Shiu-Chung Au of Tufts Medical Center, Boston.

Photos courtesy Dr. David J. Goldberg

Dr. Au presented an open-label, 24-week study of 20 patients with moderate to severe palmoplantar psoriasis that was refractory to topical corticosteroids. Dosing of ustekinumab (Stelara) was as for plaque-type psoriasis: The 11 patients weighing less than 100 kg received 45 mg subcutaneously at weeks 0, 4, and 16, whereas the 9 patients weighing 100 kg or more received 90 mg on the same schedule.

The primary study end point was a Palm-Sole PGA (Physician’s Global Assessment) score of 0 or 1 at week 16. The average baseline score on this 0-5 measure of induration, erythema, and scaling was 4. The primary end point was achieved in 1 of 11 patients on the 45-mg dose, compared with 6 of 9 on the 90-mg dose (J. Dermatolog. Treat. 2012 May 8. [Epub ahead of print]). Of 20 patients, 12 improved at least 2 points on the Palm-Sole PGA at week 16.

In addition, significant improvements were documented with respect to the secondary end points for pain and quality of life. The mean pain score on a 100-point visual analog scale improved from 51 at week 0 to 29 at week 16, and held steady with a score of 30 at 24 weeks. Moreover, the mean score on the Dermatology Life Quality Index improved from 13.9 at baseline to 6.05 at week 16 and to 6.18 at week 24.

Ustekinumab was well tolerated with no serious adverse events.

Palmoplantar psoriasis is an uncommon variant of psoriasis that constitutes a therapeutic challenge, noted Dr. Au. It can be disfiguring and disabling, even though affected patients don’t necessarily have a large area of body surface involvement. The condition is characterized by fissures and sterile inflammatory pustules, in addition to classic well-demarcated psoriasis plaques. Affected patients experience considerable skin pain, often accompanied by a burning sensation. Some patients are unable to walk.

Clinically, palmoplantar psoriasis can look like other diseases, including palmoplantar pustulosis, dyshidrotic eczema, tinea pedis, and contact dermatitis, he explained. To help eliminate other possible diagnoses in the differential diagnosis, participants in the ustekinumab study had to have at least one classic psoriasis plaque somewhere other than the palms and soles.

Current treatment of palmoplantar psoriasis has been unsatisfactory, noted Dr. Au. No standard therapy is recognized, which was the impetus for studying ustekinumab. Future studies will look at employing the 90-mg dose in patients who weigh less than 100 kg and/or administering the 45-mg dose more frequently than the current standard every 3 months, he added.

In response to an audience question, he noted that responsiveness to the 90-mg dose was not weight related. The average weight in the high-dose group was 250 pounds, and the three nonresponders weighed in similarly to the six responders.

This investigator-initiated ustekinumab study was funded by a grant from Janssen Pharmaceuticals. Dr. Au reported having no financial conflicts. Senior investigator Dr. Alice B. Gottlieb reported having numerous industry relationships.

RALEIGH, N.C. – Psoriasis patients are at a nearly fourfold increased risk of developing Crohn’s disease, and the risk is higher in psoriatic arthritis patients.

These findings from 174,646 prospectively followed participants in the Nurses’ Health Study and the Nurses’ Health Study II are consistent with the results of genomewide association studies which have found susceptibility genes common to both psoriasis and inflammatory bowel disease, especially genes in the interleukin-23 pathway, Dr. Wenqing Li said at the annual meeting of the Society for Investigative Dermatology.

"Further understanding of the mechanisms that mediate both psoriasis and Crohn’s disease could eventually lead to elucidation of new targets for interventions that may modulate the incidence or activity of both diseases," added Dr. Li of Harvard Medical School, Boston.

Of note, the psoriasis patients were not at significantly increased risk for developing ulcerative colitis. This suggests that psoriasis may share fewer overlapping pathways with ulcerative colitis than it does with Crohn’s disease, he continued.

Women in the Nurses’ Health Study were prospectively followed from 1996 to 2008, whereas those in the NHS II were followed from 1991 to 2005. During follow-up, there were 188 incident cases of Crohn’s disease and 240 of ulcerative colitis in the study population. All diagnoses of inflammatory bowel disease were confirmed by two gastroenterologists blinded as to whether or not the affected patients also had psoriasis, Dr. Li noted.

The combined analysis of the two studies included 47,618 person-years of prospective follow-up of psoriasis patients and 2,401,883 person-years of follow-up of participants without psoriasis. The psoriasis patients had an age-adjusted 3.74-fold increased risk of developing Crohn’s disease.

Having psoriasis was still an independent risk factor for Crohn’s disease, with an associated 3.5-fold relative risk, in a multivariate analysis that was adjusted for body mass index, physical activity, smoking status, alcohol consumption, use of oral contraceptives, and postmenopausal hormone therapy as well as age.

Based upon 5,661 person-years of prospective follow-up of subjects with psoriasis and comorbid psoriatic arthritis, affected patients had a 6.8-fold increased of Crohn’s disease in a multivariate analysis.

Multivariate analysis was appropriate because patients with psoriasis had a higher BMI, tended to be older, consumed more alcohol, and were less physically active than were those without psoriasis. The psoriasis patients were also more likely to be current smokers, users of oral contraceptives, and current users of postmenopausal hormone therapy.

The risk of new-onset Crohn’s disease was significantly greater among psoriasis patients whose dermatologic disease was diagnosed when they were younger than 40 years than it was among those diagnosed later in life. The risk was also greater in those with at least a 10-year history of active psoriasis. However, as 87% of patients with psoriasis had mild skin disease based upon the involved body surface area, this study didn’t have sufficient power to determine if the risk of Crohn’s disease was greater in individuals with more severe psoriasis, according to Dr. Li.

To ensure that the increased risk of inflammatory bowel disease associated with having psoriasis wasn’t in some way affected by the use of tumor necrosis factor inhibitors to treat psoriasis, Dr. Li and coinvestigators conducted a separate analysis restricting follow-up through 2004, the year the biologic therapies were approved for psoriasis. This didn’t change the results.

The studies were sponsored by the National Institutes of Health. Dr. Li reported having no financial conflicts.

RALEIGH, N.C. – Psoriasis patients are at a nearly fourfold increased risk of developing Crohn’s disease, and the risk is higher in psoriatic arthritis patients.

These findings from 174,646 prospectively followed participants in the Nurses’ Health Study and the Nurses’ Health Study II are consistent with the results of genomewide association studies which have found susceptibility genes common to both psoriasis and inflammatory bowel disease, especially genes in the interleukin-23 pathway, Dr. Wenqing Li said at the annual meeting of the Society for Investigative Dermatology.

"Further understanding of the mechanisms that mediate both psoriasis and Crohn’s disease could eventually lead to elucidation of new targets for interventions that may modulate the incidence or activity of both diseases," added Dr. Li of Harvard Medical School, Boston.

Of note, the psoriasis patients were not at significantly increased risk for developing ulcerative colitis. This suggests that psoriasis may share fewer overlapping pathways with ulcerative colitis than it does with Crohn’s disease, he continued.

Women in the Nurses’ Health Study were prospectively followed from 1996 to 2008, whereas those in the NHS II were followed from 1991 to 2005. During follow-up, there were 188 incident cases of Crohn’s disease and 240 of ulcerative colitis in the study population. All diagnoses of inflammatory bowel disease were confirmed by two gastroenterologists blinded as to whether or not the affected patients also had psoriasis, Dr. Li noted.

The combined analysis of the two studies included 47,618 person-years of prospective follow-up of psoriasis patients and 2,401,883 person-years of follow-up of participants without psoriasis. The psoriasis patients had an age-adjusted 3.74-fold increased risk of developing Crohn’s disease.

Having psoriasis was still an independent risk factor for Crohn’s disease, with an associated 3.5-fold relative risk, in a multivariate analysis that was adjusted for body mass index, physical activity, smoking status, alcohol consumption, use of oral contraceptives, and postmenopausal hormone therapy as well as age.

Based upon 5,661 person-years of prospective follow-up of subjects with psoriasis and comorbid psoriatic arthritis, affected patients had a 6.8-fold increased of Crohn’s disease in a multivariate analysis.

Multivariate analysis was appropriate because patients with psoriasis had a higher BMI, tended to be older, consumed more alcohol, and were less physically active than were those without psoriasis. The psoriasis patients were also more likely to be current smokers, users of oral contraceptives, and current users of postmenopausal hormone therapy.

The risk of new-onset Crohn’s disease was significantly greater among psoriasis patients whose dermatologic disease was diagnosed when they were younger than 40 years than it was among those diagnosed later in life. The risk was also greater in those with at least a 10-year history of active psoriasis. However, as 87% of patients with psoriasis had mild skin disease based upon the involved body surface area, this study didn’t have sufficient power to determine if the risk of Crohn’s disease was greater in individuals with more severe psoriasis, according to Dr. Li.

To ensure that the increased risk of inflammatory bowel disease associated with having psoriasis wasn’t in some way affected by the use of tumor necrosis factor inhibitors to treat psoriasis, Dr. Li and coinvestigators conducted a separate analysis restricting follow-up through 2004, the year the biologic therapies were approved for psoriasis. This didn’t change the results.

The studies were sponsored by the National Institutes of Health. Dr. Li reported having no financial conflicts.

RALEIGH, N.C. – Psoriasis patients are at a nearly fourfold increased risk of developing Crohn’s disease, and the risk is higher in psoriatic arthritis patients.

These findings from 174,646 prospectively followed participants in the Nurses’ Health Study and the Nurses’ Health Study II are consistent with the results of genomewide association studies which have found susceptibility genes common to both psoriasis and inflammatory bowel disease, especially genes in the interleukin-23 pathway, Dr. Wenqing Li said at the annual meeting of the Society for Investigative Dermatology.

"Further understanding of the mechanisms that mediate both psoriasis and Crohn’s disease could eventually lead to elucidation of new targets for interventions that may modulate the incidence or activity of both diseases," added Dr. Li of Harvard Medical School, Boston.

Of note, the psoriasis patients were not at significantly increased risk for developing ulcerative colitis. This suggests that psoriasis may share fewer overlapping pathways with ulcerative colitis than it does with Crohn’s disease, he continued.

Women in the Nurses’ Health Study were prospectively followed from 1996 to 2008, whereas those in the NHS II were followed from 1991 to 2005. During follow-up, there were 188 incident cases of Crohn’s disease and 240 of ulcerative colitis in the study population. All diagnoses of inflammatory bowel disease were confirmed by two gastroenterologists blinded as to whether or not the affected patients also had psoriasis, Dr. Li noted.

The combined analysis of the two studies included 47,618 person-years of prospective follow-up of psoriasis patients and 2,401,883 person-years of follow-up of participants without psoriasis. The psoriasis patients had an age-adjusted 3.74-fold increased risk of developing Crohn’s disease.

Having psoriasis was still an independent risk factor for Crohn’s disease, with an associated 3.5-fold relative risk, in a multivariate analysis that was adjusted for body mass index, physical activity, smoking status, alcohol consumption, use of oral contraceptives, and postmenopausal hormone therapy as well as age.

Based upon 5,661 person-years of prospective follow-up of subjects with psoriasis and comorbid psoriatic arthritis, affected patients had a 6.8-fold increased of Crohn’s disease in a multivariate analysis.

Multivariate analysis was appropriate because patients with psoriasis had a higher BMI, tended to be older, consumed more alcohol, and were less physically active than were those without psoriasis. The psoriasis patients were also more likely to be current smokers, users of oral contraceptives, and current users of postmenopausal hormone therapy.

The risk of new-onset Crohn’s disease was significantly greater among psoriasis patients whose dermatologic disease was diagnosed when they were younger than 40 years than it was among those diagnosed later in life. The risk was also greater in those with at least a 10-year history of active psoriasis. However, as 87% of patients with psoriasis had mild skin disease based upon the involved body surface area, this study didn’t have sufficient power to determine if the risk of Crohn’s disease was greater in individuals with more severe psoriasis, according to Dr. Li.

To ensure that the increased risk of inflammatory bowel disease associated with having psoriasis wasn’t in some way affected by the use of tumor necrosis factor inhibitors to treat psoriasis, Dr. Li and coinvestigators conducted a separate analysis restricting follow-up through 2004, the year the biologic therapies were approved for psoriasis. This didn’t change the results.

The studies were sponsored by the National Institutes of Health. Dr. Li reported having no financial conflicts.

RALEIGH, N.C. – Psoriasis patients who possess the HLA-Cw6 allele appear to be protected against the increased risk of cardiovascular and metabolic comorbidities associated with the disease.

In a study that included 199 psoriasis patients under the age of 40, those who carried the histocompatibility antigen HLA-Cw6 allele had a 66% reduction in the prevalence of comorbid hypertension and a 72% reduction in dyslipidemia, compared with HLA-Cw6-negative psoriasis patients, according to Dr. Trilokraj Tejasvi of the University of Michigan, Ann Arbor.

This is a particularly intriguing finding, he noted, because previous studies have demonstrated that HLA-Cw6-positive psoriasis patients tend to have more severe skin disease, an earlier age at disease onset, higher rates of the guttate and eruptive forms of psoriasis as well as Koebner phenomenon, and more extensive disease (J. Invest. Dermatol. 2002;118:362-5).

Moreover, other studies have shown that patients with more severe psoriasis tend to have higher rates of comorbid cardiovascular and metabolic disorders. For example, a large recent study that included 4,065 psoriasis patients aged 45-65 years and nearly 41,000 age- and physician practice-matched controls showed that the risk of comorbid metabolic syndrome increased from 1.2-fold in patients with mild psoriasis to twofold in those with severe psoriasis, compared with controls (J. Invest. Dermatol. 2012;132:556-62).

A strikingly similar twofold increased risk of the metabolic syndrome in psoriasis patients was recently reported based upon data from the National Health and Nutrition Examination Survey for 2003-2006 (Arch. Dermatol. 2011;147:419-24).

Since neither the NHANES psoriasis patients nor those in the U.K. study underwent genotyping, there is no way of knowing what proportion of those who were HLA-Cw6-positive had the metabolic syndrome, Dr. Tejasvi noted.

In a recent, still-to-be-published genome-wide association study, he and his colleagues found that all known psoriasis-associated single nucleotide polymorphisms explained roughly 22% of the disease’s heritability – and nearly half of were because of genes located at HLA-C.

The study included 1,134 psoriasis patients and 1,174 unaffected controls who underwent genomic DNA analysis. He and his coinvestigators examined the rates of hypertension, dyslipidemia, acute MI, and diabetes mellitus in the two groups.

One analysis was restricted to the 199 psoriasis patients and 392 controls under age 40, since the comorbid conditions under scrutiny tend to less frequently in younger people. In this under-40 analysis, the prevalence of diabetes wasn’t significantly different between psoriasis patients and controls. Neither was a history of MI.

However, 15% of the younger psoriasis patients carried the diagnosis of hypertension, compared with 6.8% of controls, and 29% of the psoriasis patients were dyslipidemic, compared with 10.5% of controls. Thus, psoriasis patients under age 40 were 2.2-fold more likely than controls to be hypertensive and 2.75-fold more likely to be dyslipidemic. Both differences were highly significant.

The prevalence of hypertension among 80 HLA-Cw6-positive psoriasis patients under age 40 was 7.5%, compared with 22% in HLA-Cw6-negative psoriasis patients under age 40. And the prevalence of dyslipidemia in the HLA-Cw6-positive group was 12.5% vs. 44% in the HLA-Cw6-negative psoriasis patients.

The under-40 psoriatic HLA-Cw6 carriers and noncarriers were essentially the same in terms of body mass index – a mean of 28 kg/m2 in both groups – and in mean age at evaluation, which was 28 years in the HLa-Cw6-positive patients and 29 years in the HLA-Cw6-negative cohort, Dr. Tejasvi reported.

Several key findings stood out in the analysis of the overall study population comprised of 1,134 psoriasis patients and 1,174 controls. One was that among control patients without psoriasis, HLA-Cw6 status was unrelated to comorbid hypertension, dyslipidemia, diabetes, or a positive history for MI. And in the full group of psoriasis patients, hypertension and dyslipidemia remained significantly less common among those who were HLA-Cw6-negative, although the association was less robust than in the below-40 subgroup. Specifically, HLA-Cw6 carriers with psoriasis were 24% less likely to be hypertensive and 25% less likely to have dyslipidemia than psoriatic HLAL-Cw6 noncarriers.

Dr. Tejasvi commented that an HLA-Cw6 protective effect against hypertension and dyslipidemia isn’t the only possible explanation for the lower rates of these two components of the metabolic syndrome found in HLA-Cw6-positive psoriasis patients. The alternate possibility is that HLA-Cw6 noncarrier status in psoriasis patients is associated with other genetic loci that increase the risk of dyslipidemia and hypertension. Sorting this out will require a prospective study with a large sample size.

The study was sponsored by the National Institutes of Health. Dr. Tejasvi reported having no financial conflicts.

RALEIGH, N.C. – Psoriasis patients who possess the HLA-Cw6 allele appear to be protected against the increased risk of cardiovascular and metabolic comorbidities associated with the disease.

In a study that included 199 psoriasis patients under the age of 40, those who carried the histocompatibility antigen HLA-Cw6 allele had a 66% reduction in the prevalence of comorbid hypertension and a 72% reduction in dyslipidemia, compared with HLA-Cw6-negative psoriasis patients, according to Dr. Trilokraj Tejasvi of the University of Michigan, Ann Arbor.

This is a particularly intriguing finding, he noted, because previous studies have demonstrated that HLA-Cw6-positive psoriasis patients tend to have more severe skin disease, an earlier age at disease onset, higher rates of the guttate and eruptive forms of psoriasis as well as Koebner phenomenon, and more extensive disease (J. Invest. Dermatol. 2002;118:362-5).

Moreover, other studies have shown that patients with more severe psoriasis tend to have higher rates of comorbid cardiovascular and metabolic disorders. For example, a large recent study that included 4,065 psoriasis patients aged 45-65 years and nearly 41,000 age- and physician practice-matched controls showed that the risk of comorbid metabolic syndrome increased from 1.2-fold in patients with mild psoriasis to twofold in those with severe psoriasis, compared with controls (J. Invest. Dermatol. 2012;132:556-62).

A strikingly similar twofold increased risk of the metabolic syndrome in psoriasis patients was recently reported based upon data from the National Health and Nutrition Examination Survey for 2003-2006 (Arch. Dermatol. 2011;147:419-24).

Since neither the NHANES psoriasis patients nor those in the U.K. study underwent genotyping, there is no way of knowing what proportion of those who were HLA-Cw6-positive had the metabolic syndrome, Dr. Tejasvi noted.

In a recent, still-to-be-published genome-wide association study, he and his colleagues found that all known psoriasis-associated single nucleotide polymorphisms explained roughly 22% of the disease’s heritability – and nearly half of were because of genes located at HLA-C.

The study included 1,134 psoriasis patients and 1,174 unaffected controls who underwent genomic DNA analysis. He and his coinvestigators examined the rates of hypertension, dyslipidemia, acute MI, and diabetes mellitus in the two groups.

One analysis was restricted to the 199 psoriasis patients and 392 controls under age 40, since the comorbid conditions under scrutiny tend to less frequently in younger people. In this under-40 analysis, the prevalence of diabetes wasn’t significantly different between psoriasis patients and controls. Neither was a history of MI.

However, 15% of the younger psoriasis patients carried the diagnosis of hypertension, compared with 6.8% of controls, and 29% of the psoriasis patients were dyslipidemic, compared with 10.5% of controls. Thus, psoriasis patients under age 40 were 2.2-fold more likely than controls to be hypertensive and 2.75-fold more likely to be dyslipidemic. Both differences were highly significant.

The prevalence of hypertension among 80 HLA-Cw6-positive psoriasis patients under age 40 was 7.5%, compared with 22% in HLA-Cw6-negative psoriasis patients under age 40. And the prevalence of dyslipidemia in the HLA-Cw6-positive group was 12.5% vs. 44% in the HLA-Cw6-negative psoriasis patients.

The under-40 psoriatic HLA-Cw6 carriers and noncarriers were essentially the same in terms of body mass index – a mean of 28 kg/m2 in both groups – and in mean age at evaluation, which was 28 years in the HLa-Cw6-positive patients and 29 years in the HLA-Cw6-negative cohort, Dr. Tejasvi reported.

Several key findings stood out in the analysis of the overall study population comprised of 1,134 psoriasis patients and 1,174 controls. One was that among control patients without psoriasis, HLA-Cw6 status was unrelated to comorbid hypertension, dyslipidemia, diabetes, or a positive history for MI. And in the full group of psoriasis patients, hypertension and dyslipidemia remained significantly less common among those who were HLA-Cw6-negative, although the association was less robust than in the below-40 subgroup. Specifically, HLA-Cw6 carriers with psoriasis were 24% less likely to be hypertensive and 25% less likely to have dyslipidemia than psoriatic HLAL-Cw6 noncarriers.

Dr. Tejasvi commented that an HLA-Cw6 protective effect against hypertension and dyslipidemia isn’t the only possible explanation for the lower rates of these two components of the metabolic syndrome found in HLA-Cw6-positive psoriasis patients. The alternate possibility is that HLA-Cw6 noncarrier status in psoriasis patients is associated with other genetic loci that increase the risk of dyslipidemia and hypertension. Sorting this out will require a prospective study with a large sample size.

The study was sponsored by the National Institutes of Health. Dr. Tejasvi reported having no financial conflicts.

RALEIGH, N.C. – Psoriasis patients who possess the HLA-Cw6 allele appear to be protected against the increased risk of cardiovascular and metabolic comorbidities associated with the disease.

In a study that included 199 psoriasis patients under the age of 40, those who carried the histocompatibility antigen HLA-Cw6 allele had a 66% reduction in the prevalence of comorbid hypertension and a 72% reduction in dyslipidemia, compared with HLA-Cw6-negative psoriasis patients, according to Dr. Trilokraj Tejasvi of the University of Michigan, Ann Arbor.

This is a particularly intriguing finding, he noted, because previous studies have demonstrated that HLA-Cw6-positive psoriasis patients tend to have more severe skin disease, an earlier age at disease onset, higher rates of the guttate and eruptive forms of psoriasis as well as Koebner phenomenon, and more extensive disease (J. Invest. Dermatol. 2002;118:362-5).

Moreover, other studies have shown that patients with more severe psoriasis tend to have higher rates of comorbid cardiovascular and metabolic disorders. For example, a large recent study that included 4,065 psoriasis patients aged 45-65 years and nearly 41,000 age- and physician practice-matched controls showed that the risk of comorbid metabolic syndrome increased from 1.2-fold in patients with mild psoriasis to twofold in those with severe psoriasis, compared with controls (J. Invest. Dermatol. 2012;132:556-62).

A strikingly similar twofold increased risk of the metabolic syndrome in psoriasis patients was recently reported based upon data from the National Health and Nutrition Examination Survey for 2003-2006 (Arch. Dermatol. 2011;147:419-24).

Since neither the NHANES psoriasis patients nor those in the U.K. study underwent genotyping, there is no way of knowing what proportion of those who were HLA-Cw6-positive had the metabolic syndrome, Dr. Tejasvi noted.

In a recent, still-to-be-published genome-wide association study, he and his colleagues found that all known psoriasis-associated single nucleotide polymorphisms explained roughly 22% of the disease’s heritability – and nearly half of were because of genes located at HLA-C.

The study included 1,134 psoriasis patients and 1,174 unaffected controls who underwent genomic DNA analysis. He and his coinvestigators examined the rates of hypertension, dyslipidemia, acute MI, and diabetes mellitus in the two groups.

One analysis was restricted to the 199 psoriasis patients and 392 controls under age 40, since the comorbid conditions under scrutiny tend to less frequently in younger people. In this under-40 analysis, the prevalence of diabetes wasn’t significantly different between psoriasis patients and controls. Neither was a history of MI.

However, 15% of the younger psoriasis patients carried the diagnosis of hypertension, compared with 6.8% of controls, and 29% of the psoriasis patients were dyslipidemic, compared with 10.5% of controls. Thus, psoriasis patients under age 40 were 2.2-fold more likely than controls to be hypertensive and 2.75-fold more likely to be dyslipidemic. Both differences were highly significant.

The prevalence of hypertension among 80 HLA-Cw6-positive psoriasis patients under age 40 was 7.5%, compared with 22% in HLA-Cw6-negative psoriasis patients under age 40. And the prevalence of dyslipidemia in the HLA-Cw6-positive group was 12.5% vs. 44% in the HLA-Cw6-negative psoriasis patients.

The under-40 psoriatic HLA-Cw6 carriers and noncarriers were essentially the same in terms of body mass index – a mean of 28 kg/m2 in both groups – and in mean age at evaluation, which was 28 years in the HLa-Cw6-positive patients and 29 years in the HLA-Cw6-negative cohort, Dr. Tejasvi reported.

Several key findings stood out in the analysis of the overall study population comprised of 1,134 psoriasis patients and 1,174 controls. One was that among control patients without psoriasis, HLA-Cw6 status was unrelated to comorbid hypertension, dyslipidemia, diabetes, or a positive history for MI. And in the full group of psoriasis patients, hypertension and dyslipidemia remained significantly less common among those who were HLA-Cw6-negative, although the association was less robust than in the below-40 subgroup. Specifically, HLA-Cw6 carriers with psoriasis were 24% less likely to be hypertensive and 25% less likely to have dyslipidemia than psoriatic HLAL-Cw6 noncarriers.

Dr. Tejasvi commented that an HLA-Cw6 protective effect against hypertension and dyslipidemia isn’t the only possible explanation for the lower rates of these two components of the metabolic syndrome found in HLA-Cw6-positive psoriasis patients. The alternate possibility is that HLA-Cw6 noncarrier status in psoriasis patients is associated with other genetic loci that increase the risk of dyslipidemia and hypertension. Sorting this out will require a prospective study with a large sample size.

The study was sponsored by the National Institutes of Health. Dr. Tejasvi reported having no financial conflicts.

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Vigorous physical activity – particularly running and aerobics – appears to protect women against developing psoriasis, according to a report published online May 21 in the Archives of Dermatology.

In what the researchers described as the first prospective study to examine the association between physical activity and the onset of psoriasis, women who reported participating in at least 20.9 MET (metabolic equivalent)–hours per week of vigorous exercise – the equivalent of 105 minutes of running or 180 minutes of swimming or playing tennis – showed a 25%-30% lower risk of incident psoriasis, compared with women who reported no vigorous exercise, said Hillary C. Frankel of the department of dermatology at Brigham and Women’s Hospital, Boston, and her associates.

"This amount of vigorous activity is roughly equivalent to the current U.S. Department of Health and Human Services recommendation for greater health benefits," they noted.

Physical activity has been associated with a decreased risk of several disorders that are characterized by systemic inflammation, including type 2 diabetes, colon cancer, coronary artery disease, and breast cancer. Until now, only a few cross-sectional studies have examined the role of physical activity in psoriasis, and those have yielded inconsistent results.

Ms. Frankel and her associates prospectively assessed the relationship between customary physical activity and incident psoriasis using data from the Nurses' Health Study. That study included a longitudinal cohort of more than 116,000 female registered nurses residing in 15 states who were aged 25-42 years at baseline in 1989, and who completed biennial questionnaires about their health.

For this study, the researchers focused on 86,665 participants who did not have psoriasis at baseline and who answered detailed questions about their physical activity in 1991, 1997, and 2001. This included 1,026 study participants who developed psoriasis during the 14-year follow-up period.

The total physical activity score, measured in MET-hours per week, was inversely related to the risk of developing psoriasis in a dose-dependent fashion. The most physically active quintile of the cohort had a relative risk of 0.71 of developing psoriasis, compared with the least-active quintile.

In a separate analysis by type of physical activity, only certain vigorous physical activity was found to be protective against psoriasis.

After adjustment for age, smoking status, alcohol intake, and other vigorous activity, women who ran for more than 1 hour per week had a relative risk of 0.37, compared with those who did not run. Similarly, women who participated in at least 4 hours per week of aerobics had an adjusted relative risk of 0.54, compared with those who did not do aerobics. Both trends were statistically significant.

However, no such association was seen among women who participated in other vigorous activities such as bicycling, swimming, and playing tennis. And walking – regardless of the amount of time devoted to it – was not associated with reduced risk of psoriasis.

"The highly variable intensity at which these activities are performed may account for this finding," the investigators said (Arch. Dermatol. 2012 May 21 [doi:10.1001/archdermatol.2012.943]).

The mechanism by which vigorous exercise might reduce psoriasis risk is not yet known, but "it is biologically plausible that [it] could modulate a state of chronic inflammation and/or immune activation that predisposes women to develop psoriasis," Ms. Frankel and her colleagues said.

Physical activity is known to lower levels of proinflammatory cytokines and elevate levels of anti-inflammatory cytokines. It also has beneficial effects on mood, decreasing anxiety and stress; stress is believed to incite psoriasis by activating the immune system, they added.

This study was supported by the National Institutes of Health and the department of dermatology at Brigham and Women’s Hospital. Study coauthor Dr. Abrar A. Qureshi reported ties to Novartis. No other potential financial conflicts of interest were reported.

Digital ulcers are a frequent manifestation of systemic sclerosis, affecting approximately half of all patients with the multisystem connective tissue disorder. Often persistent and recurring, these ischemic wounds tend to be slow-healing and difficult to manage. In addition to pain and disability, severe complications such as tissue loss, infection, gangrene, autoamputation, and septicemia can exacerbate the clinical burden by an order of magnitude, according to Christopher Denton, Ph.D., director of the Center for Rheumatology at University College London.

In an effort to better understand the clinical and antibody characteristics, disease course, and outcomes associated with digital ulcers, Dr. Denton and his colleagues established the Digital Ulcers Outcome Registry, a European, multicenter, observational registry of systemic sclerosis (SSc) patients with ongoing digital ulcer disease. To date, the registry includes demographic, clinical, and treatment information for more than 2,500 patients, providing investigators with valuable insight into the nature and progression of digital ulcer disease in this at-risk population.

In this month’s column, Dr. Denton discusses the progress of the registry as well as the information that investigators have gleaned from it.

Question: What are the objectives for the Digital Ulcers Outcome (DUO) Registry?

Dr. Denton: The DUO registry is a prospective observational program for SSc patients with digital ulcers. In 2008, physicians at participating centers began enrolling consenting consecutive patients with ongoing digital ulcers associated with SSc. The objectives of the registry include tracking key information on the clinical course and outcome of digital ulcers, regardless of their treatment regimen, although an express goal is to collect safety information on the use of the dual endothelin receptor antagonist bosentan, which is approved in Europe for reducing the number of new digital ulcers in SSc.

The DUO registry is a noninterventional registry. Patients receive standard medical care and follow-up as determined by their physician. The data collected include patient demographics, SSc disease duration, classification of underlying disease, internal organ manifestations, autoantibodies, history of interventions and complications related to digital ulcers, ongoing complications related to digital ulcers, ongoing medications, and functional assessment based on a disease-specific questionnaire. Additionally, the presence of antinuclear antibodies, anti-scleroderma-70 antibodies, anticentromere antibodies, anti-RNA polymerase 3, anti-U1-ribonucleoprotein, and anti-U3-ribonucleoprotein is recorded, as well as all serology tests and other tests that have been performed.

Question: Based on the registry data collected to date, which SSc patients are most likely to develop digital ulcers?

Dr. Denton: Digital ulcers appear to develop earliest and most frequently in patients with diffuse cutaneous SSc, anti-scleroderma-70 antibodies, or both. In our recent review, we reported that among 2,439 patients enrolled through November 2010, most of whom had limited or diffuse cutaneous SSc, digital ulcers developed earlier in patients with the diffuse cutaneous subtype (Ann. Rheum. Dis. 2012;71:718-21). Patients who tested positive for anti-scleroderma-70 antibodies, in particular, developed first digital ulcers at a significantly younger mean age (44.7 years) than those who tested positive for anticentromere antibodies (ACAs) (50.1 years). Similarly, patients positive for anti-scleroderma-70 antibodies were younger than ACA-positive patients at the onset of the first symptoms of Raynaud’s phenomenon, and had less time between the onset of Raynaud’s and development of their first digital ulcer.

Question: What are some of the most common digital ulcer–associated complications that have been reported, and which patients are most vulnerable?

Dr. Denton: Infections requiring antibiotics, gangrene, and amputation were frequent complications across all of the major disease subsets. Patients positive for anti-scleroderma-70 were twice as likely to develop lung fibrosis compared with ACA-positive patients, and they were also more likely to have heart manifestations. Both lung fibrosis and heart disease are consistent with studies indicating more severe disease in patients positive for anti-scleroderma-70.

Question: Can the risk of the development of digital ulcers be minimized or prevented in SSc?

Dr. Denton: Treatment with the oral endothelin receptor antagonist bosentan appears to be effective in preventing new digital ulcers. Last year we reported results from the RAPIDS-2 randomized, double-blind, placebo-controlled trial (Ann. Rheum. Dis. 2011;70:32-8) showing that treatment with bosentan reduced the occurrence of new digital ulcers by 30% over 24 weeks compared with placebo in patients with at least one active digital ulcer at the time of enrollment. The effect was greater in patients who entered the trial with more digital ulcers.

Question: What is the optimal treatment of digital ulcers in this population?

Dr. Denton: There is still a great clinical need for a tolerable, effective therapeutic option for improving tissue integrity and viability and promoting ulcer healing, in addition to reducing the formation of new ulcers. Although bosentan has been approved [in Europe] for the prevention of new digital ulcers in patients with SSc and ongoing digital ulcer disease, our findings [from the RAPIDS-2 trial] suggest that the treatment has no effect on digital ulcer healing. Vasodilators may improve digital circulation, and small studies suggest that the prostanoids epoprostenol and iloprost may improve healing, but controlled data supporting their use is lacking. The DUO registry may provide data that informs clinical trials of targeted therapies.

Dr. Denton reported that he has financial relationships with
Actelion Pharmaceuticals, Aspreva, Biovitrum, Digna,
Encysive Pharmaceuticals, Genzyme, and Pfizer.

Digital ulcers are a frequent manifestation of systemic sclerosis, affecting approximately half of all patients with the multisystem connective tissue disorder. Often persistent and recurring, these ischemic wounds tend to be slow-healing and difficult to manage. In addition to pain and disability, severe complications such as tissue loss, infection, gangrene, autoamputation, and septicemia can exacerbate the clinical burden by an order of magnitude, according to Christopher Denton, Ph.D., director of the Center for Rheumatology at University College London.

In an effort to better understand the clinical and antibody characteristics, disease course, and outcomes associated with digital ulcers, Dr. Denton and his colleagues established the Digital Ulcers Outcome Registry, a European, multicenter, observational registry of systemic sclerosis (SSc) patients with ongoing digital ulcer disease. To date, the registry includes demographic, clinical, and treatment information for more than 2,500 patients, providing investigators with valuable insight into the nature and progression of digital ulcer disease in this at-risk population.

In this month’s column, Dr. Denton discusses the progress of the registry as well as the information that investigators have gleaned from it.

Question: What are the objectives for the Digital Ulcers Outcome (DUO) Registry?

Dr. Denton: The DUO registry is a prospective observational program for SSc patients with digital ulcers. In 2008, physicians at participating centers began enrolling consenting consecutive patients with ongoing digital ulcers associated with SSc. The objectives of the registry include tracking key information on the clinical course and outcome of digital ulcers, regardless of their treatment regimen, although an express goal is to collect safety information on the use of the dual endothelin receptor antagonist bosentan, which is approved in Europe for reducing the number of new digital ulcers in SSc.

The DUO registry is a noninterventional registry. Patients receive standard medical care and follow-up as determined by their physician. The data collected include patient demographics, SSc disease duration, classification of underlying disease, internal organ manifestations, autoantibodies, history of interventions and complications related to digital ulcers, ongoing complications related to digital ulcers, ongoing medications, and functional assessment based on a disease-specific questionnaire. Additionally, the presence of antinuclear antibodies, anti-scleroderma-70 antibodies, anticentromere antibodies, anti-RNA polymerase 3, anti-U1-ribonucleoprotein, and anti-U3-ribonucleoprotein is recorded, as well as all serology tests and other tests that have been performed.

Question: Based on the registry data collected to date, which SSc patients are most likely to develop digital ulcers?

Dr. Denton: Digital ulcers appear to develop earliest and most frequently in patients with diffuse cutaneous SSc, anti-scleroderma-70 antibodies, or both. In our recent review, we reported that among 2,439 patients enrolled through November 2010, most of whom had limited or diffuse cutaneous SSc, digital ulcers developed earlier in patients with the diffuse cutaneous subtype (Ann. Rheum. Dis. 2012;71:718-21). Patients who tested positive for anti-scleroderma-70 antibodies, in particular, developed first digital ulcers at a significantly younger mean age (44.7 years) than those who tested positive for anticentromere antibodies (ACAs) (50.1 years). Similarly, patients positive for anti-scleroderma-70 antibodies were younger than ACA-positive patients at the onset of the first symptoms of Raynaud’s phenomenon, and had less time between the onset of Raynaud’s and development of their first digital ulcer.

Question: What are some of the most common digital ulcer–associated complications that have been reported, and which patients are most vulnerable?

Dr. Denton: Infections requiring antibiotics, gangrene, and amputation were frequent complications across all of the major disease subsets. Patients positive for anti-scleroderma-70 were twice as likely to develop lung fibrosis compared with ACA-positive patients, and they were also more likely to have heart manifestations. Both lung fibrosis and heart disease are consistent with studies indicating more severe disease in patients positive for anti-scleroderma-70.

Question: Can the risk of the development of digital ulcers be minimized or prevented in SSc?

Dr. Denton: Treatment with the oral endothelin receptor antagonist bosentan appears to be effective in preventing new digital ulcers. Last year we reported results from the RAPIDS-2 randomized, double-blind, placebo-controlled trial (Ann. Rheum. Dis. 2011;70:32-8) showing that treatment with bosentan reduced the occurrence of new digital ulcers by 30% over 24 weeks compared with placebo in patients with at least one active digital ulcer at the time of enrollment. The effect was greater in patients who entered the trial with more digital ulcers.

Question: What is the optimal treatment of digital ulcers in this population?

Dr. Denton: There is still a great clinical need for a tolerable, effective therapeutic option for improving tissue integrity and viability and promoting ulcer healing, in addition to reducing the formation of new ulcers. Although bosentan has been approved [in Europe] for the prevention of new digital ulcers in patients with SSc and ongoing digital ulcer disease, our findings [from the RAPIDS-2 trial] suggest that the treatment has no effect on digital ulcer healing. Vasodilators may improve digital circulation, and small studies suggest that the prostanoids epoprostenol and iloprost may improve healing, but controlled data supporting their use is lacking. The DUO registry may provide data that informs clinical trials of targeted therapies.

Dr. Denton reported that he has financial relationships with
Actelion Pharmaceuticals, Aspreva, Biovitrum, Digna,
Encysive Pharmaceuticals, Genzyme, and Pfizer.

Digital ulcers are a frequent manifestation of systemic sclerosis, affecting approximately half of all patients with the multisystem connective tissue disorder. Often persistent and recurring, these ischemic wounds tend to be slow-healing and difficult to manage. In addition to pain and disability, severe complications such as tissue loss, infection, gangrene, autoamputation, and septicemia can exacerbate the clinical burden by an order of magnitude, according to Christopher Denton, Ph.D., director of the Center for Rheumatology at University College London.

In an effort to better understand the clinical and antibody characteristics, disease course, and outcomes associated with digital ulcers, Dr. Denton and his colleagues established the Digital Ulcers Outcome Registry, a European, multicenter, observational registry of systemic sclerosis (SSc) patients with ongoing digital ulcer disease. To date, the registry includes demographic, clinical, and treatment information for more than 2,500 patients, providing investigators with valuable insight into the nature and progression of digital ulcer disease in this at-risk population.

In this month’s column, Dr. Denton discusses the progress of the registry as well as the information that investigators have gleaned from it.

Question: What are the objectives for the Digital Ulcers Outcome (DUO) Registry?

Dr. Denton: The DUO registry is a prospective observational program for SSc patients with digital ulcers. In 2008, physicians at participating centers began enrolling consenting consecutive patients with ongoing digital ulcers associated with SSc. The objectives of the registry include tracking key information on the clinical course and outcome of digital ulcers, regardless of their treatment regimen, although an express goal is to collect safety information on the use of the dual endothelin receptor antagonist bosentan, which is approved in Europe for reducing the number of new digital ulcers in SSc.

The DUO registry is a noninterventional registry. Patients receive standard medical care and follow-up as determined by their physician. The data collected include patient demographics, SSc disease duration, classification of underlying disease, internal organ manifestations, autoantibodies, history of interventions and complications related to digital ulcers, ongoing complications related to digital ulcers, ongoing medications, and functional assessment based on a disease-specific questionnaire. Additionally, the presence of antinuclear antibodies, anti-scleroderma-70 antibodies, anticentromere antibodies, anti-RNA polymerase 3, anti-U1-ribonucleoprotein, and anti-U3-ribonucleoprotein is recorded, as well as all serology tests and other tests that have been performed.

Question: Based on the registry data collected to date, which SSc patients are most likely to develop digital ulcers?

Dr. Denton: Digital ulcers appear to develop earliest and most frequently in patients with diffuse cutaneous SSc, anti-scleroderma-70 antibodies, or both. In our recent review, we reported that among 2,439 patients enrolled through November 2010, most of whom had limited or diffuse cutaneous SSc, digital ulcers developed earlier in patients with the diffuse cutaneous subtype (Ann. Rheum. Dis. 2012;71:718-21). Patients who tested positive for anti-scleroderma-70 antibodies, in particular, developed first digital ulcers at a significantly younger mean age (44.7 years) than those who tested positive for anticentromere antibodies (ACAs) (50.1 years). Similarly, patients positive for anti-scleroderma-70 antibodies were younger than ACA-positive patients at the onset of the first symptoms of Raynaud’s phenomenon, and had less time between the onset of Raynaud’s and development of their first digital ulcer.

Question: What are some of the most common digital ulcer–associated complications that have been reported, and which patients are most vulnerable?

Dr. Denton: Infections requiring antibiotics, gangrene, and amputation were frequent complications across all of the major disease subsets. Patients positive for anti-scleroderma-70 were twice as likely to develop lung fibrosis compared with ACA-positive patients, and they were also more likely to have heart manifestations. Both lung fibrosis and heart disease are consistent with studies indicating more severe disease in patients positive for anti-scleroderma-70.

Question: Can the risk of the development of digital ulcers be minimized or prevented in SSc?

Dr. Denton: Treatment with the oral endothelin receptor antagonist bosentan appears to be effective in preventing new digital ulcers. Last year we reported results from the RAPIDS-2 randomized, double-blind, placebo-controlled trial (Ann. Rheum. Dis. 2011;70:32-8) showing that treatment with bosentan reduced the occurrence of new digital ulcers by 30% over 24 weeks compared with placebo in patients with at least one active digital ulcer at the time of enrollment. The effect was greater in patients who entered the trial with more digital ulcers.

Question: What is the optimal treatment of digital ulcers in this population?

Dr. Denton: There is still a great clinical need for a tolerable, effective therapeutic option for improving tissue integrity and viability and promoting ulcer healing, in addition to reducing the formation of new ulcers. Although bosentan has been approved [in Europe] for the prevention of new digital ulcers in patients with SSc and ongoing digital ulcer disease, our findings [from the RAPIDS-2 trial] suggest that the treatment has no effect on digital ulcer healing. Vasodilators may improve digital circulation, and small studies suggest that the prostanoids epoprostenol and iloprost may improve healing, but controlled data supporting their use is lacking. The DUO registry may provide data that informs clinical trials of targeted therapies.

Dr. Denton reported that he has financial relationships with
Actelion Pharmaceuticals, Aspreva, Biovitrum, Digna,
Encysive Pharmaceuticals, Genzyme, and Pfizer.