Psoriasis

RALEIGH, N.C. – Current screening instruments that are designed to identify the 20%-30% of psoriasis patients who have psoriatic arthritis leave much to be desired, Dr. Jessica A. Walsh asserted at the annual meeting of the Society for Investigative Dermatology.

She asked 189 psoriasis patients who are enrolled in the Utah Psoriasis Initiative to take three of the most popular psoriatic arthritis self-administered screening questionnaires. The tests’ sensitivities and specificities proved markedly lower than previously reported in the instruments’ validation studies.

Moreover, all three tests – the Psoriatic Arthritis Screening and Evaluation (PASE), the Psoriasis Epidemiology Screening Project (PEST), and the Toronto Psoriatic Arthritis Screen (ToPAS) – differentiated only poorly among psoriatic arthritis, other types of arthritis, and fibromyalgia.

And the tests had other weak points: "The instruments were less sensitive in patients with lower psoriatic arthritis disease activity, fewer disease features, and shorter disease duration. This is suboptimal because these instruments were designed to help capture early disease," said Dr. Walsh, a rheumatologist at the University of Utah, Salt Lake City.

She is involved in a project aimed at reducing delays in diagnosis of psoriatic arthritis, an underdiagnosed condition in psoriasis patients. According to a 2011 National Psoriasis Foundation survey, 29% of psoriatic arthritis patients don’t receive their diagnosis until 2 years or more after onset of symptoms. That’s bad news, because early diagnosis and treatment help minimize symptoms, enhance quality of life, and prevent joint damage. Studies show that nearly one-half of psoriatic arthritis patients develop radiographic evidence of erosive damage within 2 years of symptom onset. Treatment can slow that progressive erosion.

All 189 psoriasis patients in Dr. Walsh’s study had musculoskeletal complaints of sufficient magnitude that they were willing to take the three screening tests in order to receive a free rheumatologic evaluation. A total of 137 patients had psoriatic arthritis, and two-thirds of them had already been diagnosed with the disease prior to participation in her study.

The gold standard to which the screening tests were compared was Dr. Walsh’s diagnostic evaluation, which included laboratory testing and imaging as warranted. When there was a discrepancy between any of the screening tests and her diagnosis, as occurred in 138 cases, a second rheumatologist with expertise in psoriatic arthritis was called in as a tiebreaker.

The sensitivities of PACE, PEST, and ToPAS were 68%, 85%, and 75%, respectively. The specificities were worse, at 50%, 45%, and 55%. These are in sharp contrast to previous studies, in which the test sensitivities were 88%-97%, with reported specificities of 79%-95%, she noted.

The frequency of discrepancies between patient responses to specific screening questions and the rheumatologic exam findings varied among the test instruments in a way that caused Dr. Walsh to believe that combining selected questions from each test and, in some cases, modifying the wording might result in a hybrid-screening instrument with improved performance. She plans to test that hypothesis.

Dr. Abrar A. Qureshi, one of the developers of PASE, said he and his coworkers have been thinking along the same lines.

"We’re working on a shorter version of PASE that might work better. Nine of the 15 questions on PASE seem to track well with inflammatory arthritis," commented Dr. Qureshi, vice chairman of the department of dermatology at Brigham and Women’s Hospital, Boston.

The Utah Psoriasis Initiative is funded by the University of Utah department of dermatology. Dr. Walsh reported having no financial conflicts.

RALEIGH, N.C. – Current screening instruments that are designed to identify the 20%-30% of psoriasis patients who have psoriatic arthritis leave much to be desired, Dr. Jessica A. Walsh asserted at the annual meeting of the Society for Investigative Dermatology.

She asked 189 psoriasis patients who are enrolled in the Utah Psoriasis Initiative to take three of the most popular psoriatic arthritis self-administered screening questionnaires. The tests’ sensitivities and specificities proved markedly lower than previously reported in the instruments’ validation studies.

Moreover, all three tests – the Psoriatic Arthritis Screening and Evaluation (PASE), the Psoriasis Epidemiology Screening Project (PEST), and the Toronto Psoriatic Arthritis Screen (ToPAS) – differentiated only poorly among psoriatic arthritis, other types of arthritis, and fibromyalgia.

And the tests had other weak points: "The instruments were less sensitive in patients with lower psoriatic arthritis disease activity, fewer disease features, and shorter disease duration. This is suboptimal because these instruments were designed to help capture early disease," said Dr. Walsh, a rheumatologist at the University of Utah, Salt Lake City.

She is involved in a project aimed at reducing delays in diagnosis of psoriatic arthritis, an underdiagnosed condition in psoriasis patients. According to a 2011 National Psoriasis Foundation survey, 29% of psoriatic arthritis patients don’t receive their diagnosis until 2 years or more after onset of symptoms. That’s bad news, because early diagnosis and treatment help minimize symptoms, enhance quality of life, and prevent joint damage. Studies show that nearly one-half of psoriatic arthritis patients develop radiographic evidence of erosive damage within 2 years of symptom onset. Treatment can slow that progressive erosion.

All 189 psoriasis patients in Dr. Walsh’s study had musculoskeletal complaints of sufficient magnitude that they were willing to take the three screening tests in order to receive a free rheumatologic evaluation. A total of 137 patients had psoriatic arthritis, and two-thirds of them had already been diagnosed with the disease prior to participation in her study.

The gold standard to which the screening tests were compared was Dr. Walsh’s diagnostic evaluation, which included laboratory testing and imaging as warranted. When there was a discrepancy between any of the screening tests and her diagnosis, as occurred in 138 cases, a second rheumatologist with expertise in psoriatic arthritis was called in as a tiebreaker.

The sensitivities of PACE, PEST, and ToPAS were 68%, 85%, and 75%, respectively. The specificities were worse, at 50%, 45%, and 55%. These are in sharp contrast to previous studies, in which the test sensitivities were 88%-97%, with reported specificities of 79%-95%, she noted.

The frequency of discrepancies between patient responses to specific screening questions and the rheumatologic exam findings varied among the test instruments in a way that caused Dr. Walsh to believe that combining selected questions from each test and, in some cases, modifying the wording might result in a hybrid-screening instrument with improved performance. She plans to test that hypothesis.

Dr. Abrar A. Qureshi, one of the developers of PASE, said he and his coworkers have been thinking along the same lines.

"We’re working on a shorter version of PASE that might work better. Nine of the 15 questions on PASE seem to track well with inflammatory arthritis," commented Dr. Qureshi, vice chairman of the department of dermatology at Brigham and Women’s Hospital, Boston.

The Utah Psoriasis Initiative is funded by the University of Utah department of dermatology. Dr. Walsh reported having no financial conflicts.

RALEIGH, N.C. – Current screening instruments that are designed to identify the 20%-30% of psoriasis patients who have psoriatic arthritis leave much to be desired, Dr. Jessica A. Walsh asserted at the annual meeting of the Society for Investigative Dermatology.

She asked 189 psoriasis patients who are enrolled in the Utah Psoriasis Initiative to take three of the most popular psoriatic arthritis self-administered screening questionnaires. The tests’ sensitivities and specificities proved markedly lower than previously reported in the instruments’ validation studies.

Moreover, all three tests – the Psoriatic Arthritis Screening and Evaluation (PASE), the Psoriasis Epidemiology Screening Project (PEST), and the Toronto Psoriatic Arthritis Screen (ToPAS) – differentiated only poorly among psoriatic arthritis, other types of arthritis, and fibromyalgia.

And the tests had other weak points: "The instruments were less sensitive in patients with lower psoriatic arthritis disease activity, fewer disease features, and shorter disease duration. This is suboptimal because these instruments were designed to help capture early disease," said Dr. Walsh, a rheumatologist at the University of Utah, Salt Lake City.

She is involved in a project aimed at reducing delays in diagnosis of psoriatic arthritis, an underdiagnosed condition in psoriasis patients. According to a 2011 National Psoriasis Foundation survey, 29% of psoriatic arthritis patients don’t receive their diagnosis until 2 years or more after onset of symptoms. That’s bad news, because early diagnosis and treatment help minimize symptoms, enhance quality of life, and prevent joint damage. Studies show that nearly one-half of psoriatic arthritis patients develop radiographic evidence of erosive damage within 2 years of symptom onset. Treatment can slow that progressive erosion.

All 189 psoriasis patients in Dr. Walsh’s study had musculoskeletal complaints of sufficient magnitude that they were willing to take the three screening tests in order to receive a free rheumatologic evaluation. A total of 137 patients had psoriatic arthritis, and two-thirds of them had already been diagnosed with the disease prior to participation in her study.

The gold standard to which the screening tests were compared was Dr. Walsh’s diagnostic evaluation, which included laboratory testing and imaging as warranted. When there was a discrepancy between any of the screening tests and her diagnosis, as occurred in 138 cases, a second rheumatologist with expertise in psoriatic arthritis was called in as a tiebreaker.

The sensitivities of PACE, PEST, and ToPAS were 68%, 85%, and 75%, respectively. The specificities were worse, at 50%, 45%, and 55%. These are in sharp contrast to previous studies, in which the test sensitivities were 88%-97%, with reported specificities of 79%-95%, she noted.

The frequency of discrepancies between patient responses to specific screening questions and the rheumatologic exam findings varied among the test instruments in a way that caused Dr. Walsh to believe that combining selected questions from each test and, in some cases, modifying the wording might result in a hybrid-screening instrument with improved performance. She plans to test that hypothesis.

Dr. Abrar A. Qureshi, one of the developers of PASE, said he and his coworkers have been thinking along the same lines.

"We’re working on a shorter version of PASE that might work better. Nine of the 15 questions on PASE seem to track well with inflammatory arthritis," commented Dr. Qureshi, vice chairman of the department of dermatology at Brigham and Women’s Hospital, Boston.

The Utah Psoriasis Initiative is funded by the University of Utah department of dermatology. Dr. Walsh reported having no financial conflicts.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

BERLIN – Tocilizumab monotherapy worked substantially better than adalimumab monotherapy in a head-to-head randomized trial of 326 rheumatoid arthritis patients, suggesting that the newer drug tocilizumab has superior efficacy compared with drugs that block tumor necrosis factor, at least when methotrexate isn’t coadministered.

After 24 weeks of treatment, tocilizumab monotherapy produced remission of rheumatoid arthritis (RA) in 40% of patients, based on their disease activity score in 28 joints (DAS28), compared with an 11% remission rate in patients on adalimumab monotherapy, a significant difference, Dr. Cem Gabay reported at the annual European Congress of Rheumatology.

This is the first direct RA comparison of representatives of these two drug classes, both of which block cytokines, said Dr. Gabay, professor of pathology and immunology at the University of Geneva. Both tocilizumab (Actemra) and adalimumab (Humira) have Food and Drug Administration labeling for the treatment of RA.

"Anti-TNF [tumor necrosis factor] drugs remain the first biologic drugs to try, based on EULAR recommendations, but we showed that if a patient is on monotherapy, tocilizumab might be the better choice," Dr. Gabay said in an interview.

"If a patient is on methotrexate and tolerates methotrexate, there is no reason to stop," and those patients should continue to get a TNF inhibitor. "But many patients don’t tolerate methotrexate, and in these patients tocilizumab may be the choice for a biologic as monotherapy." About a third of RA patients who receive a biologic drug get it as monotherapy and are not on concomitant therapy with a synthetic, disease-modifying antirheumatic drug (DMARD) such as methotrexate, usually because they don’t tolerate those drugs or because their preference is to avoid them.

"This needs to be confirmed by other studies, but according to these new data, when patients cannot tolerate a synthetic DMARD they will do better on tocilizumab than with an anti-TNF drug," Dr. Gabay said. "But for the majority of patients [who are on synthetic DMARD treatment], an anti-TNF drug remains the first line. They have been around for 10 years, and are much more studied than tocilizumab."

The finding is important for RA practice because "we don’t have many head-to-head studies of biologics," commented Dr. Xavier Mariette, professor and head of rheumatology at Bicetre Hospital in Paris. But he questioned the fairness of using adalimumab as the study’s representative anti-TNF drug, noting its documented immunogenicity, especially when used in monotherapy. "Other monotherapy would have been more appropriate," he said.

In response, Dr. Gabay highlighted the separation in average DAS28 scores that occurred after 8 weeks of treatment between the two study arms, the point when patients on tocilizumab began to have significantly lower scores than the adalimumab patients. The difference seems to occur too soon to result from an immune reaction to adalimumab, Dr. Gabay said.

The ADACTA trial enrolled 326 adults with RA at 82 centers in 15 countries including the United States. Enrollment criteria included having RA for at least 6 months and a DAS28 score of more than 5.1. All patients were naive for biologic drugs, but they could have had prior or current treatment with methotrexate or other synthetic DMARDs. All DMARDs were withdrawn at least 2 weeks before the study began. The patients had a mean age of 53 years, 80% were women, their average RA duration was more than 6 years, they had a history with average of two DMARDs, slightly more than half were on an oral steroid, and their mean DAS28 score was about 6.7.

The researchers randomized patients to receive 8 mg/kg tocilizumab intravenously every 4 weeks, or 40 mg of subcutaneous adalimumab every 2 weeks. Patients also received placebo treatments to blind everyone to the active-drug assignments.

For the study’s primary end point, average change in DAS28 score from baseline to 24 weeks on treatment, the reductions averaged 1.8 points in the adalimumab group and 3.3 points in the tocilizumab group, a significant difference. Low disease activity, defined as a DAS28 score of 3.2 or less, occurred in 20% of the adalimumab patients and in 52% of those on tocilizumab, also a significant difference. A 20% improvement by the criteria of the American College of Rheumatology (ACR20) occurred in 49% of the adalimumab patients, and their ACR50 and ACR70 rates were 28% and 18%, respectively. In the tocilizumab patients, the ACR20/50/70 rates were 65%, 47%, and 33%, respectively.

The rates of serious adverse events, infections, and serious infections were all similar in the two treatment arms. Infections occurred in 42% of the adalimumab patients and in 48% of those on tocilizumab, and serious infections occurred in 3% of both groups. Serious adverse events occurred in 10% of the adalimumab patients and in 12% of those on tocilizumab. Patients on tocilizumab had moderately higher rates of elevated liver enzymes. The tocilizumab patients had a 31% rate of enzymes elevated from above the upper limit of normal (ULN) to 2.5-fold the ULN, compared with 25% of the adalimumab patients; and liver enzyme elevations of 2.6-5.0 times the ULN occurred in 6% of the tocilizumab patients and in 2% of those on adalimumab. Tocilizumab showed "no new or unexpected adverse effects," Dr. Gabay said.

The study was sponsored by Roche, the company that markets tocilizumab. Dr. Gabay reported receiving research support from and being a consultant to Roche and several other drug companies. Dr. Mariette reported receiving research support from Roche and several other drug companies.

RALEIGH, N.C. – At 2 weeks after psoriasis patients received their first dose of the investigational interleukin-17 inhibitor ixekizumab, their gene expression pattern resembled that of healthy controls.

At the annual meeting of the Society for Investigative Dermatology, Dr. James G. Krueger presented a translational medicine study aimed at defining the impact that turning off IL-17 signaling has on pathological tissue structures, molecular pathways, and biomarkers.

His conclusion: "I think these data suggest IL-17 is the central cytokine driving pathogenesis in psoriasis," said Dr. Krueger of Rockefeller University in New York.

Eight psoriasis patients received a subcutaneous 150-mg dose of ixekizumab at weeks 0, 2, and 4 and underwent skin biopsies at weeks 0, 2, and 6. He compared their inflammatory gene expression profiles 2 weeks into treatment vs. those obtained from 15 psoriasis patients 2 weeks after beginning treatment with etanercept (at 50 mg twice weekly for 12 weeks).

IL-17 blockade with ixekizumab proved to have a greater impact on the expression of inflammatory genes known to be associated with psoriasis than did tumor necrosis factor inhibition via etanercept. Ixekizumab resulted in greater-than-75% normalization of expression of 643 of these inflammatory genes, compared with 104 with etanercept.

The structural result of IL-17 blockade was reversal by week 6 of the epidermal hyperplasia that is the hallmark of psoriasis, he added.

Two of the eight patients on the ixekizumab 150-mg regimen achieved PASI 75 (that is, a 75% improvement from baseline on the Psoriasis Area and Severity Index) in 2 weeks. That’s remarkably fast improvement, Dr. Krueger noted. By week 6, all eight patients had achieved PASI 75.

Another point in favor of IL-17’s being a central cytokine driving psoriasis is that ixekizumab shut down not only the IL-17A target genes downstream, but also genes controlling the production of key cytokines located upstream, including interferon-gamma and IL-22, he noted.

Phase III trials investigating ixekizumab for psoriasis are underway. The drug is also being investigated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Dr. Krueger is a consultant to Eli Lilly, which funded the study and is developing ixekizumab as a treatment for psoriasis.

RALEIGH, N.C. – At 2 weeks after psoriasis patients received their first dose of the investigational interleukin-17 inhibitor ixekizumab, their gene expression pattern resembled that of healthy controls.

At the annual meeting of the Society for Investigative Dermatology, Dr. James G. Krueger presented a translational medicine study aimed at defining the impact that turning off IL-17 signaling has on pathological tissue structures, molecular pathways, and biomarkers.

His conclusion: "I think these data suggest IL-17 is the central cytokine driving pathogenesis in psoriasis," said Dr. Krueger of Rockefeller University in New York.

Eight psoriasis patients received a subcutaneous 150-mg dose of ixekizumab at weeks 0, 2, and 4 and underwent skin biopsies at weeks 0, 2, and 6. He compared their inflammatory gene expression profiles 2 weeks into treatment vs. those obtained from 15 psoriasis patients 2 weeks after beginning treatment with etanercept (at 50 mg twice weekly for 12 weeks).

IL-17 blockade with ixekizumab proved to have a greater impact on the expression of inflammatory genes known to be associated with psoriasis than did tumor necrosis factor inhibition via etanercept. Ixekizumab resulted in greater-than-75% normalization of expression of 643 of these inflammatory genes, compared with 104 with etanercept.

The structural result of IL-17 blockade was reversal by week 6 of the epidermal hyperplasia that is the hallmark of psoriasis, he added.

Two of the eight patients on the ixekizumab 150-mg regimen achieved PASI 75 (that is, a 75% improvement from baseline on the Psoriasis Area and Severity Index) in 2 weeks. That’s remarkably fast improvement, Dr. Krueger noted. By week 6, all eight patients had achieved PASI 75.

Another point in favor of IL-17’s being a central cytokine driving psoriasis is that ixekizumab shut down not only the IL-17A target genes downstream, but also genes controlling the production of key cytokines located upstream, including interferon-gamma and IL-22, he noted.

Phase III trials investigating ixekizumab for psoriasis are underway. The drug is also being investigated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Dr. Krueger is a consultant to Eli Lilly, which funded the study and is developing ixekizumab as a treatment for psoriasis.

RALEIGH, N.C. – At 2 weeks after psoriasis patients received their first dose of the investigational interleukin-17 inhibitor ixekizumab, their gene expression pattern resembled that of healthy controls.

At the annual meeting of the Society for Investigative Dermatology, Dr. James G. Krueger presented a translational medicine study aimed at defining the impact that turning off IL-17 signaling has on pathological tissue structures, molecular pathways, and biomarkers.

His conclusion: "I think these data suggest IL-17 is the central cytokine driving pathogenesis in psoriasis," said Dr. Krueger of Rockefeller University in New York.

Eight psoriasis patients received a subcutaneous 150-mg dose of ixekizumab at weeks 0, 2, and 4 and underwent skin biopsies at weeks 0, 2, and 6. He compared their inflammatory gene expression profiles 2 weeks into treatment vs. those obtained from 15 psoriasis patients 2 weeks after beginning treatment with etanercept (at 50 mg twice weekly for 12 weeks).

IL-17 blockade with ixekizumab proved to have a greater impact on the expression of inflammatory genes known to be associated with psoriasis than did tumor necrosis factor inhibition via etanercept. Ixekizumab resulted in greater-than-75% normalization of expression of 643 of these inflammatory genes, compared with 104 with etanercept.

The structural result of IL-17 blockade was reversal by week 6 of the epidermal hyperplasia that is the hallmark of psoriasis, he added.

Two of the eight patients on the ixekizumab 150-mg regimen achieved PASI 75 (that is, a 75% improvement from baseline on the Psoriasis Area and Severity Index) in 2 weeks. That’s remarkably fast improvement, Dr. Krueger noted. By week 6, all eight patients had achieved PASI 75.

Another point in favor of IL-17’s being a central cytokine driving psoriasis is that ixekizumab shut down not only the IL-17A target genes downstream, but also genes controlling the production of key cytokines located upstream, including interferon-gamma and IL-22, he noted.

Phase III trials investigating ixekizumab for psoriasis are underway. The drug is also being investigated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Dr. Krueger is a consultant to Eli Lilly, which funded the study and is developing ixekizumab as a treatment for psoriasis.

BERLIN – The proteasome inhibitor bortezomib shows considerable promise as a novel treatment for refractory SLE, according to Dr. Reinhard E. Voll.

"I think it’s useful as an induction therapy; then you can go on with regular maintenance therapy," he said at the annual European Congress of Rheumatology.

He presented a series of 13 patients with SLE refractory to conventional immunosuppressive drugs and antimalarials treated off label with bortezomib (Velcade) at three German university medical centers. Ten patients had refractory active lupus nephritis.

All patients responded to bortezomib with significant reductions in anti–double-stranded DNA antibody titers and SLE Disease Activity Index (SLEDAI) scores. Proteinuria decreased within 6 weeks in all patients with active lupus nephritis, one of whom achieved normal protein excretion by 4 months, according to Dr. Voll, a rheumatologist at the University of Freiburg (Germany).

The mean baseline SLEDAI score was 14.3, dropping to 5.2 after two to a maximum of four courses of bortezomib. In the three patients with the highest baseline SLEDAIs of 20 or 21, their scores at the end of bortezomib therapy were 4, 6, and 7.

Patients remained on mycophenolate mofetil and antimalarials during treatment with bortezomib. Once the patients displayed marked improvement, the proteasome inhibitor was stopped. During 6 months of follow-up post bortezomib, SLEDAIs remained the same as, and in some cases lower than, at the time bortezomib was stopped.

Bortezomib is approved for the treatment of relapsed multiple myeloma and for mantle cell lymphoma.

The SLE patients received bortezomib intravenously at a dose of 1.3 mg/m² of body surface area on days 1, 4, and 8, and in some cases also on day 11 of a given treatment cycle. Patients typically received 20 mg of dexamethasone together with bortezomib. Up to four cycles could be given, with 10-14 days in between.

Dr. Voll said he limits himself to three treatment days per cycle because three of the seven patients who got a fourth dose on day 11 at other centers developed peripheral polyneuropathies, the drug’s major side effect. Bortezomib-induced peripheral neuropathy resolves upon treatment discontinuation. But the problem didn’t occur in patients treated on three days per cycle.

One patient developed a moderate transient thrombocytopenia after four treatment cycles, but no other hematologic toxicities occurred.

Because of concern that a drug that depletes pathogenic antibodies might also lower protective vaccine antibody titers, the investigators measured titers to hepatitis B surface antigen and tetanus toxoid before and after bortezomib. Vaccine antibody titers dropped by up to 50% but still remained in the protective zone.

In an interview, Dr. Voll explained that he grew interested in investigating bortezomib because of a conviction he shares with others that one of the major reasons SLE and other antibody-mediated diseases can become highly refractory to conventional therapies is that affected patients have long-lived plasma cells secreting copious quantities of pathogenic antibodies. These self-perpetuating plasma cells are resistant to conventional SLE medications, including intravenous pulsed-dose cyclophosphamide, rituximab, and antimalarials (Nat. Rev. Rheumatol. 2011;7:170-8).

"We thought bortezomib might be toxic not only to myeloma cells, but to normal plasma cells. We moved to mouse models of lupus and found we could deplete the long-lived plasma cells very nicely with bortezomib. And we could also resolve lupus nephritis," he recalled, citing his earlier published study (Nat. Med. 2008;14:748-55).

The rheumatologist speculated that the proteasome inhibitor might also be useful in very severe cases of allergic disease. A colleague treated a patient with food allergies so severe that the patient had been unable to eat solid food for 2 years and was becoming suicidal as a result.

"After the second course of bortezomib, he could eat one solid meal per day, and his IgE antibody titers went way down. It was really amazing," Dr. Voll said.

In light of the highly promising 13-patient series, the next logical step would be a formal clinical trial of bortezomib in refractory SLE. Bortezomib’s manufacturer, Millenium Pharmaceuticals, has a related drug with less associated peripheral neuropathy that’s well along in development; the company has indicated interest in sponsoring a clinical trial of the new drug in refractory SLE, according to the rheumatologist.

The bortezomib used in the 13-patient series was paid for by the German health care system. Dr. Voll reported having no relevant financial conflicts.

BERLIN – The proteasome inhibitor bortezomib shows considerable promise as a novel treatment for refractory SLE, according to Dr. Reinhard E. Voll.

"I think it’s useful as an induction therapy; then you can go on with regular maintenance therapy," he said at the annual European Congress of Rheumatology.

He presented a series of 13 patients with SLE refractory to conventional immunosuppressive drugs and antimalarials treated off label with bortezomib (Velcade) at three German university medical centers. Ten patients had refractory active lupus nephritis.

All patients responded to bortezomib with significant reductions in anti–double-stranded DNA antibody titers and SLE Disease Activity Index (SLEDAI) scores. Proteinuria decreased within 6 weeks in all patients with active lupus nephritis, one of whom achieved normal protein excretion by 4 months, according to Dr. Voll, a rheumatologist at the University of Freiburg (Germany).

The mean baseline SLEDAI score was 14.3, dropping to 5.2 after two to a maximum of four courses of bortezomib. In the three patients with the highest baseline SLEDAIs of 20 or 21, their scores at the end of bortezomib therapy were 4, 6, and 7.

Patients remained on mycophenolate mofetil and antimalarials during treatment with bortezomib. Once the patients displayed marked improvement, the proteasome inhibitor was stopped. During 6 months of follow-up post bortezomib, SLEDAIs remained the same as, and in some cases lower than, at the time bortezomib was stopped.

Bortezomib is approved for the treatment of relapsed multiple myeloma and for mantle cell lymphoma.

The SLE patients received bortezomib intravenously at a dose of 1.3 mg/m² of body surface area on days 1, 4, and 8, and in some cases also on day 11 of a given treatment cycle. Patients typically received 20 mg of dexamethasone together with bortezomib. Up to four cycles could be given, with 10-14 days in between.

Dr. Voll said he limits himself to three treatment days per cycle because three of the seven patients who got a fourth dose on day 11 at other centers developed peripheral polyneuropathies, the drug’s major side effect. Bortezomib-induced peripheral neuropathy resolves upon treatment discontinuation. But the problem didn’t occur in patients treated on three days per cycle.

One patient developed a moderate transient thrombocytopenia after four treatment cycles, but no other hematologic toxicities occurred.

Because of concern that a drug that depletes pathogenic antibodies might also lower protective vaccine antibody titers, the investigators measured titers to hepatitis B surface antigen and tetanus toxoid before and after bortezomib. Vaccine antibody titers dropped by up to 50% but still remained in the protective zone.

In an interview, Dr. Voll explained that he grew interested in investigating bortezomib because of a conviction he shares with others that one of the major reasons SLE and other antibody-mediated diseases can become highly refractory to conventional therapies is that affected patients have long-lived plasma cells secreting copious quantities of pathogenic antibodies. These self-perpetuating plasma cells are resistant to conventional SLE medications, including intravenous pulsed-dose cyclophosphamide, rituximab, and antimalarials (Nat. Rev. Rheumatol. 2011;7:170-8).

"We thought bortezomib might be toxic not only to myeloma cells, but to normal plasma cells. We moved to mouse models of lupus and found we could deplete the long-lived plasma cells very nicely with bortezomib. And we could also resolve lupus nephritis," he recalled, citing his earlier published study (Nat. Med. 2008;14:748-55).

The rheumatologist speculated that the proteasome inhibitor might also be useful in very severe cases of allergic disease. A colleague treated a patient with food allergies so severe that the patient had been unable to eat solid food for 2 years and was becoming suicidal as a result.

"After the second course of bortezomib, he could eat one solid meal per day, and his IgE antibody titers went way down. It was really amazing," Dr. Voll said.

In light of the highly promising 13-patient series, the next logical step would be a formal clinical trial of bortezomib in refractory SLE. Bortezomib’s manufacturer, Millenium Pharmaceuticals, has a related drug with less associated peripheral neuropathy that’s well along in development; the company has indicated interest in sponsoring a clinical trial of the new drug in refractory SLE, according to the rheumatologist.

The bortezomib used in the 13-patient series was paid for by the German health care system. Dr. Voll reported having no relevant financial conflicts.

BERLIN – The proteasome inhibitor bortezomib shows considerable promise as a novel treatment for refractory SLE, according to Dr. Reinhard E. Voll.

"I think it’s useful as an induction therapy; then you can go on with regular maintenance therapy," he said at the annual European Congress of Rheumatology.

He presented a series of 13 patients with SLE refractory to conventional immunosuppressive drugs and antimalarials treated off label with bortezomib (Velcade) at three German university medical centers. Ten patients had refractory active lupus nephritis.

All patients responded to bortezomib with significant reductions in anti–double-stranded DNA antibody titers and SLE Disease Activity Index (SLEDAI) scores. Proteinuria decreased within 6 weeks in all patients with active lupus nephritis, one of whom achieved normal protein excretion by 4 months, according to Dr. Voll, a rheumatologist at the University of Freiburg (Germany).

The mean baseline SLEDAI score was 14.3, dropping to 5.2 after two to a maximum of four courses of bortezomib. In the three patients with the highest baseline SLEDAIs of 20 or 21, their scores at the end of bortezomib therapy were 4, 6, and 7.

Patients remained on mycophenolate mofetil and antimalarials during treatment with bortezomib. Once the patients displayed marked improvement, the proteasome inhibitor was stopped. During 6 months of follow-up post bortezomib, SLEDAIs remained the same as, and in some cases lower than, at the time bortezomib was stopped.

Bortezomib is approved for the treatment of relapsed multiple myeloma and for mantle cell lymphoma.

The SLE patients received bortezomib intravenously at a dose of 1.3 mg/m² of body surface area on days 1, 4, and 8, and in some cases also on day 11 of a given treatment cycle. Patients typically received 20 mg of dexamethasone together with bortezomib. Up to four cycles could be given, with 10-14 days in between.

Dr. Voll said he limits himself to three treatment days per cycle because three of the seven patients who got a fourth dose on day 11 at other centers developed peripheral polyneuropathies, the drug’s major side effect. Bortezomib-induced peripheral neuropathy resolves upon treatment discontinuation. But the problem didn’t occur in patients treated on three days per cycle.

One patient developed a moderate transient thrombocytopenia after four treatment cycles, but no other hematologic toxicities occurred.

Because of concern that a drug that depletes pathogenic antibodies might also lower protective vaccine antibody titers, the investigators measured titers to hepatitis B surface antigen and tetanus toxoid before and after bortezomib. Vaccine antibody titers dropped by up to 50% but still remained in the protective zone.

In an interview, Dr. Voll explained that he grew interested in investigating bortezomib because of a conviction he shares with others that one of the major reasons SLE and other antibody-mediated diseases can become highly refractory to conventional therapies is that affected patients have long-lived plasma cells secreting copious quantities of pathogenic antibodies. These self-perpetuating plasma cells are resistant to conventional SLE medications, including intravenous pulsed-dose cyclophosphamide, rituximab, and antimalarials (Nat. Rev. Rheumatol. 2011;7:170-8).

"We thought bortezomib might be toxic not only to myeloma cells, but to normal plasma cells. We moved to mouse models of lupus and found we could deplete the long-lived plasma cells very nicely with bortezomib. And we could also resolve lupus nephritis," he recalled, citing his earlier published study (Nat. Med. 2008;14:748-55).

The rheumatologist speculated that the proteasome inhibitor might also be useful in very severe cases of allergic disease. A colleague treated a patient with food allergies so severe that the patient had been unable to eat solid food for 2 years and was becoming suicidal as a result.

"After the second course of bortezomib, he could eat one solid meal per day, and his IgE antibody titers went way down. It was really amazing," Dr. Voll said.

In light of the highly promising 13-patient series, the next logical step would be a formal clinical trial of bortezomib in refractory SLE. Bortezomib’s manufacturer, Millenium Pharmaceuticals, has a related drug with less associated peripheral neuropathy that’s well along in development; the company has indicated interest in sponsoring a clinical trial of the new drug in refractory SLE, according to the rheumatologist.

The bortezomib used in the 13-patient series was paid for by the German health care system. Dr. Voll reported having no relevant financial conflicts.

Tumor necrosis factor inhibitor drugs began to dominate treatment of inflammatory diseases like rheumatoid arthritis, psoriasis, and the inflammatory bowel diseases ulcerative colitis and Crohn’s disease a little over a decade again. Now, the time when the importance of the anti-TNFs will wane and newer drugs will take their place is clearly visible on the horizon. It hasn’t happened yet, but the era of anti-TNF dominance for treating inflammatory diseases that persisted throughout the 2000s will end in the next 5 years.

The anti-TNF era began in 1998 with the approval of etanercept (Enbrel) for rheumatoid arthritis and infliximab (Remicade) to treat Crohn’s disease. In subsequent years, the list of approved anti-TNFs expanded to include adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia), and the approved indications grew to include many inflammatory disease of joints, the GI tract, and skin. The anti-TNFs revolutionized inflammatory disease treatment and made treatment to remission possible for many patients.

Courtesy Bassil Dahiyat; Science

But reports from just the past month show that new agents are overtaking the anti-TNFs.

In May, I reported from Digestive Disease Week on phase III trial results with vedolizumab, which was compared against placebo for patients with ulcerative colitis. One of the study investigators noted that vedolizumab beat the placebo arm for steroid-free clinical remission by 30 percentage points. “Nothing else is that good,” Dr. William Sandborn, professor of medicine and chief of gastroenterology at the University of California, San Diego, told me, and the benchmark he had in mind was the performance of the anti-TNFs in similar patients.

More recently, at the European Congress of Rheumatology earlier this month I heard a report on a head-to-head comparison of the anti-IL-6 drug tocilizumab (Actemra) and the anti-TNF adalimumab in patients with rheumatoid arthritis. After 24 weeks of monotherapy, patients on tocilizumab had nearly a fourfold higher remission rate than patients on adalimumab. Though the monotherapy trial design did not mimic the way most rheumatoid arthritis patients get treated, the new drug tocilizumab absolutely blew adalimumab out of the water in a rare head-to-head comparison among different classes of anti-inflammatory drugs.

And at the same meeting several talks highlighted another new anti-inflammatory class of agents coming soon to the U.S. market, the Janus kinase (JAK) inhibitors, such as tofacitinib, which is expected to received FDA approval later this summer. Phase III results show that tofacitinib has safety and efficacy that seems at least comparable to anti-TNF drugs, with the advantage of oral dosing.

Vedolizumab, tocilizumab, and tofacitinib are just the tip of new waves of anti-inflammatory drugs that will soon substantially alter a landscape that the anti-TNFs have mostly had to themselves for the past 14 years. For the moment, the anti-TNFs have the advantage of a longer track record for safety, but changing that is only a matter of time.

—Mitchel Zoler (on Twitter @mitchelzoler)

Tumor necrosis factor inhibitor drugs began to dominate treatment of inflammatory diseases like rheumatoid arthritis, psoriasis, and the inflammatory bowel diseases ulcerative colitis and Crohn’s disease a little over a decade again. Now, the time when the importance of the anti-TNFs will wane and newer drugs will take their place is clearly visible on the horizon. It hasn’t happened yet, but the era of anti-TNF dominance for treating inflammatory diseases that persisted throughout the 2000s will end in the next 5 years.

The anti-TNF era began in 1998 with the approval of etanercept (Enbrel) for rheumatoid arthritis and infliximab (Remicade) to treat Crohn’s disease. In subsequent years, the list of approved anti-TNFs expanded to include adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia), and the approved indications grew to include many inflammatory disease of joints, the GI tract, and skin. The anti-TNFs revolutionized inflammatory disease treatment and made treatment to remission possible for many patients.

Courtesy Bassil Dahiyat; Science

But reports from just the past month show that new agents are overtaking the anti-TNFs.

In May, I reported from Digestive Disease Week on phase III trial results with vedolizumab, which was compared against placebo for patients with ulcerative colitis. One of the study investigators noted that vedolizumab beat the placebo arm for steroid-free clinical remission by 30 percentage points. “Nothing else is that good,” Dr. William Sandborn, professor of medicine and chief of gastroenterology at the University of California, San Diego, told me, and the benchmark he had in mind was the performance of the anti-TNFs in similar patients.

More recently, at the European Congress of Rheumatology earlier this month I heard a report on a head-to-head comparison of the anti-IL-6 drug tocilizumab (Actemra) and the anti-TNF adalimumab in patients with rheumatoid arthritis. After 24 weeks of monotherapy, patients on tocilizumab had nearly a fourfold higher remission rate than patients on adalimumab. Though the monotherapy trial design did not mimic the way most rheumatoid arthritis patients get treated, the new drug tocilizumab absolutely blew adalimumab out of the water in a rare head-to-head comparison among different classes of anti-inflammatory drugs.

And at the same meeting several talks highlighted another new anti-inflammatory class of agents coming soon to the U.S. market, the Janus kinase (JAK) inhibitors, such as tofacitinib, which is expected to received FDA approval later this summer. Phase III results show that tofacitinib has safety and efficacy that seems at least comparable to anti-TNF drugs, with the advantage of oral dosing.

Vedolizumab, tocilizumab, and tofacitinib are just the tip of new waves of anti-inflammatory drugs that will soon substantially alter a landscape that the anti-TNFs have mostly had to themselves for the past 14 years. For the moment, the anti-TNFs have the advantage of a longer track record for safety, but changing that is only a matter of time.

—Mitchel Zoler (on Twitter @mitchelzoler)

Tumor necrosis factor inhibitor drugs began to dominate treatment of inflammatory diseases like rheumatoid arthritis, psoriasis, and the inflammatory bowel diseases ulcerative colitis and Crohn’s disease a little over a decade again. Now, the time when the importance of the anti-TNFs will wane and newer drugs will take their place is clearly visible on the horizon. It hasn’t happened yet, but the era of anti-TNF dominance for treating inflammatory diseases that persisted throughout the 2000s will end in the next 5 years.

The anti-TNF era began in 1998 with the approval of etanercept (Enbrel) for rheumatoid arthritis and infliximab (Remicade) to treat Crohn’s disease. In subsequent years, the list of approved anti-TNFs expanded to include adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia), and the approved indications grew to include many inflammatory disease of joints, the GI tract, and skin. The anti-TNFs revolutionized inflammatory disease treatment and made treatment to remission possible for many patients.

Courtesy Bassil Dahiyat; Science

But reports from just the past month show that new agents are overtaking the anti-TNFs.

In May, I reported from Digestive Disease Week on phase III trial results with vedolizumab, which was compared against placebo for patients with ulcerative colitis. One of the study investigators noted that vedolizumab beat the placebo arm for steroid-free clinical remission by 30 percentage points. “Nothing else is that good,” Dr. William Sandborn, professor of medicine and chief of gastroenterology at the University of California, San Diego, told me, and the benchmark he had in mind was the performance of the anti-TNFs in similar patients.

More recently, at the European Congress of Rheumatology earlier this month I heard a report on a head-to-head comparison of the anti-IL-6 drug tocilizumab (Actemra) and the anti-TNF adalimumab in patients with rheumatoid arthritis. After 24 weeks of monotherapy, patients on tocilizumab had nearly a fourfold higher remission rate than patients on adalimumab. Though the monotherapy trial design did not mimic the way most rheumatoid arthritis patients get treated, the new drug tocilizumab absolutely blew adalimumab out of the water in a rare head-to-head comparison among different classes of anti-inflammatory drugs.

And at the same meeting several talks highlighted another new anti-inflammatory class of agents coming soon to the U.S. market, the Janus kinase (JAK) inhibitors, such as tofacitinib, which is expected to received FDA approval later this summer. Phase III results show that tofacitinib has safety and efficacy that seems at least comparable to anti-TNF drugs, with the advantage of oral dosing.

Vedolizumab, tocilizumab, and tofacitinib are just the tip of new waves of anti-inflammatory drugs that will soon substantially alter a landscape that the anti-TNFs have mostly had to themselves for the past 14 years. For the moment, the anti-TNFs have the advantage of a longer track record for safety, but changing that is only a matter of time.

—Mitchel Zoler (on Twitter @mitchelzoler)

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – Many of the classic manifestations of Behçet’s disease show a significant and previously unappreciated gender-based difference in expression, judging from the results of a new study of more than 10,000 patients.

For example, the most common form of skin involvement – erythema nodosum – is more common in women than men with Behçet’s disease, whereas papulopustular lesions and pseudofolliculitis occur more often in men with this highly variable multisystem disorder, Dr. Alfred Mahr reported at the annual European Congress of Rheumatology.

Dr. Mahr, chairman of the internal medicine department at Saint-Louis Hospital in Paris, presented a meta-analysis of the published literature on Behçet’s disease supplemented by new and unpublished data on 721 patients in the German Registry for Adamantiades-Behçet’s Disease for 1990-2011. All told, the analysis included 30 published studies, which, along with the unpublished data, comprised more than 10,000 affected patients.

The most common expression of Behçet’s disease was genital ulcers, affecting 79% of subjects, closely followed by skin involvement, at 77%. Erythema nodosum was present in 53% of patients, papulopustular skin lesions in 38%, and pseudofolliculitis in 29%.

Other frequent manifestations of Behçet’s disease included eye disease, affecting 49% of subjects, joint disease in 40%, major blood vessel involvement in 9.5%, and either deep vein or superficial thrombophlebitis in 31%.

Joint involvement was present in half of men with Behçet’s disease, compared with more than 60% of women. Even more striking was the gender difference in major vessel involvement, which affected roughly 30% of men and 10% of women. And cardiac involvement was documented in 14 men but just 1 woman.

These observations on gender differences in Behçet’s disease are important for two reasons, Dr. Mahr said: They may help in the differential diagnosis of this multisystem disorder, and they could shed light on disease pathogenesis. For example, Turkish investigators previously identified testosterone as having potentially relevant effects on neutrophil production (Clin. Exp. Rheumatol. 2007;25(4Suppl 45):46-51).

Dr. Mahr reported having no financial conflicts.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – Nonmelanoma skin cancer was the only type of malignancy found to occur at an increased rate in new 5-year follow-up data on 535 patients treated for systemic small-vessel vasculitis in four major randomized trials sponsored by the European Vasculitis Society.

With 2,650 person-years of prospective observation of 281 clinical trial participants treated for granulomatosis with polyangiitis (formerly called Wegener’s granulomatosis) and 254 treated for microscopic polyangiitis, patients with circulating antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis had a 2.78-fold greater incidence of nonmelanoma skin cancer than did the matched general population, based upon data from the European cancer registry. But no other type of cancer was significantly increased, Dr. Kerstin W.A. Westman reported at the annual European Congress of Rheumatology.

This finding came as a pleasant surprise. Earlier publications by other investigators have reported broadly elevated malignancy risks in the years following administration of the various toxic, largely cyclophosphamide-based therapeutic regimens for ANCA-associated vasculitis, noted Dr. Westman, a nephrologist at Lund (Sweden) University.

For example, Danish investigators reported significantly increased rates of bladder and prostate cancer and acute myeloid leukemia as well as nonmelanoma skin cancer in a study featuring 2,121 person-years of follow-up (J. Rheumatol.2008;35:100-5). However, the Danish patients were treated during 1973-1999, while participants in the four European Vasculitis Society randomized trials underwent treatment as recently as 2007, at which time, the research focus had shifted to trying to decrease the burden of immunosuppression while maintaining effectiveness, Dr. Westman observed. For this reason, she and her coworkers are cautiously optimistic about the limited cancer risk seen to date in their analysis.

"This may be caused by too short a period of time of follow-up or else, as we would like to think, maybe we have improved the treatment by lowering the cumulative dose of cyclophosphamide, making it less toxic. But that we don’t really know yet," she said.

Several audience members rose to relate that their own clinical experience has been that lymphoma, bladder cancer, and other malignancies crop up not within 5 years post treatment for ANCA-associated vasculitis, but 10-15 years later or even more.

"I completely agree," Dr. Westman replied. "It’s important for us to arrange longer-term follow-up to say anything conclusive about malignancy. We’re aiming for 10-year follow-up in these patients."

Still, she added, there is reason to be hopeful that some of the more recently evaluated treatment regimens are less oncogenic. For one thing, the earlier Danish study found increased rates of several types of cancer within 5 years.

Also, she cited a recent report on 445 patients with granulomatosis with polyangiitis treated during the past 4 decades at a single large German academic rheumatology center. The German investigators found no increase in malignancies. Moreover, the standardized mortality ratio – essentially, the risk of all-cause mortality compared to that of the matched general population – fell from 2.1 in patients treated during 1966-1993, to 1.41 in those treated in 1994-1998, to 1.03, meaning no increased risk, in patients treated in 1999-2002. Relapse rates during those three time periods dropped from 61% to 51% to 35% (Arthritis Rheum. 2011;63:257-66).

The four-study European Vasculitis Society cohort followed prospectively for 5 years had a median age of 61 years at the time of enrollment in the randomized trials. Of the 535 patients, 53% had antiproteinase-3 antibody positive ANCA (PR3-ANCA) and 38% had antimyeloperoxidase-positive ANCA.

Overall survival at 2 and 5 years was 85% and 78%, respectively. Mortality was 2.6-fold higher than in the age- and sex-matched general population. The mortality risk was greatest during the first year of follow up, with deaths mainly from infection or active vasculitis. After year 1, most deaths were caused by infection, cardiovascular events, or cancer.

Relapse, defined as new or worsened manifestations of ANCA-associated vasculitis requiring a change in therapy, occurred in 38% of patients. The two major risk factors for relapse were being PR3-ANCA positive or having cardiovascular involvement at enrollment.

The best 5-year overall survival was in patients younger than age 50 years at enrollment in their randomized trial. Survival was significantly worse in stepwise fashion in 50- to 60-year-olds, worse yet in 60- to 70-year-olds, and lowest of all in patients above age 70 years.

"Age matters," Dr. Westman declared.

One or more cardiovascular events occurred in 14% of the subjects during 5 years of follow-up. There were 32 cardiovascular deaths, 25 nonfatal strokes, and 42 nonfatal myocardial infarctions or revascularization procedures. Not surprisingly, older age was an independent risk factor for cardiovascular events. But PR3-ANCA–positive status proved to be an independent protector against cardiovascular events; it was associated with a 59% reduction in risk.

Also, in a new analysis of the CYCLOPS study, the most recent of the four European Vasculitis Society clinical trials, the risk of relapse was independently related to a participant’s PR3-ANCA status. The lowest relapse rate occurred in PR3-ANCA–negative patients randomized to daily oral cyclophosphamide for remission induction, while the worst relapse rate was in PR3-ANCA–positive patients assigned to pulse cyclophosphamide (Ann. Rheum. Dis. 2012;71:955-60). These findings may bring closer the day when individualized tailoring of immunosuppression might become possible.

Of patients with granulomatosis with polyangiitis, 49% experienced otolaryngologic involvement during 5 years of follow up, and in 65% of affected patients the otolaryngologic damage appeared to be permanent. An important study observation was that patients with frequent relapses were at increased risk of permanent otolaryngologic damage, Dr. Westman continued.

The four European Vasculitis Society randomized trials that tested various induction and maintenance-of-remission treatment regimens were known as NORAM, CYCAZAREM, MEPEX, and CYCLOPS.

The 5-year follow-up analysis of the four trials was funded by the European League Against Rheumatism. Dr. Westman reported having no financial conflicts.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.

"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.

The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.

"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.

The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.

These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.

"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.

The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)

Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.

Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.

Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.

"No new safety news," Dr. Mease commented.

He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.

Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.

Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.

"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.

Dr. Mease reported financial relation ships with UCB, which markets certolizumab. In addition, as a clinical trialist he has financial relationships with numerous other pharmaceutical companies that are interested in rheumatologic diseases.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – Hematopoietic stem cell transplantation appears to be a breakthrough in the treatment of poor-prognosis early diffuse cutaneous systemic sclerosis.

This complex, multistage therapy produced significantly better long-term survival than conventional pulsed-dose cyclophosphamide, despite the 10% treatment-related mortality in the first 100 days, according to the first report from the ASTIS (Autologous Stem Cell Transplantation International Scleroderma) trial.

Preliminary analysis indicates smoking canceled out the benefits of hematopoietic stem cell transplantation (HSCT) in ASTIS. If this finding is confirmed, it will create a "very tricky" ethical question: namely, should smokers with severe scleroderma be excluded from this therapy, said Dr. Jacob M. van Laar, who presented the ASTIS results at the European College of Rheumatology.

ASTIS was a 27-center European, randomized trial involving 156 patients with poor-prognosis early diffuse cutaneous scleroderma. Given that the condition’s mortality rivals that of lymphoma, the ASTIS investigators decided to study a therapy developed by oncologists for lymphoma: high-dose cyclophosphamide plus growth colony–stimulating factor, followed by collection of the patient’s CD34+ hematopoietic stem cells, another round of high-dose cyclophosphamide plus T-cell ablative therapy to ‘condition’ the immune system, then reintroduction of the CD34+ cells in order to fashion a new healthy immune system.

It’s an arduous procedure that takes place over the course of several months. The study hypothesis was that although some scleroderma patients would die early because of transplant-related complications, the net result in those who survived the procedure would be improved long-term outcomes, compared with conventional, lower-risk therapy. And that’s exactly what was seen, according to Dr. van Laar, who is professor of clinical rheumatology at Newcastle (U.K.) University.

The primary study end point was event-free survival; that is, survival without persistent organ failure involving the lungs, heart, or kidneys. During an average follow-up of 7 years, an event occurred in 19 patients in the HSCT group, compared with 27 who were randomized to standard therapy with 12 monthly intravenous pulses of cyclophosphamide at 750 mg/m².

There were 16 deaths in the HSCT arm, compared with 26 in the control group. Half of the deaths in the transplant arm were treatment related, five resulted from disease progression, and one each from sepsis, stroke, and major organ failure.

In sharp contrast, major causes of death in the control group included disease progression in 15 cases, four fatal malignancies, and three deaths from major organ failure.

The HSCT group had a 2.5-fold greater risk of mortality than did controls during the first 4 months of the study. But by 1 year, the HSCT group had a 61% lower risk of death than patients on standard therapy and, since then, they have had a 78% lower mortality extending through 8 years of follow up.

Dr. van Laar emphasized that this was a sick group of scleroderma patients. They had an average disease duration of roughly 1.5 years at enrollment, an average age of 44 years, a modified Rodnan skin score of 25, major organ involvement in a high proportion of cases, and poor physical functioning as reflected in a mean Health Assessment Questionnaire Disease Index (HAQ-DI) score of 1.3.

Many (52%) of participants were past or current smokers. In those patients, there was no significant difference in long-term event-free survival among those who received HSCT as compared with conventional therapy. But among nonsmokers, HSCT was associated with nearly a 90% long-term event-free survival rate, compared with a 60% rate if they received conventional cyclophosphamide therapy.

Asked if he thought one of the lessons of ASTIS is that smokers should not have access to HSCT, the rheumatologist replied that it’s too early to say. He and his coinvestigators haven’t yet broken down the results in terms of past vs. current smokers, number of pack-years, and other potentially relevant factors. It will be instructive as well to see if the ongoing National Institutes of Health-sponsored SCOT (Scleroderma: Cyclophosphamide Or Transplantation) trial being conducted in 226 U.S. poor-prognosis scleroderma patients confirms that smoking has a deleterious effect on long-term outcomes, Dr. van Laar added.

Dr. Xavier Mariette, Congress scientific program chairman and professor of rheumatology at Hôpital Bicêtre in Paris, took issue with the ASTIS investigators’ description of their treatment regimen as HSCT.

"It’s very important to realize it’s not the autologous stem cell transplantation that is curative, it is the high-dose cyclophosphamide that is the most important element in the combination treatment," he asserted.

Dr. van Laar disagreed. He cited evidence that high-dose cyclophosphamide alone doesn’t bring sustained long-term benefits, and other data to suggest that stem cell transplantation may mediate immune effects.

"I personally think you need the whole package," Dr. van Laar said.

Ongoing ASTIS analyses of the impact of HSCT on skin scores, functional ability, and other important questions will be completed later this year in time for presentation at the annual meeting of the American College of Rheumatology.

Scleroderma is a connective tissue disorder with a prevalence of about 1 in 10,000. Diffuse scleroderma accounts for roughly 30% of cases.

ASTIS was jointly sponsored by the European Group for Blood and Marrow Transplantation and the European League Against Rheumatism.

Dr. van Laar reported having no financial conflicts.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.

BERLIN – A 6-month course of rosuvastatin (Crestor) significantly lessened endothelial dysfunction and lowered levels of C-reactive protein in patients with systemic sclerosis, judging from findings from a new study presented at the annual European Congress of Rheumatology.

Dr. Gabriella Szucs of the department of rheumatology, University of Debrecen, Hungary, presented results from the first study of rosuvastatin therapy in systemic sclerosis (SSc), measuring the extent of endothelial dysfunction and response to the drug in the small and large vessels of these patients.

The most significant results were seen in flow-mediated dilatation (FMD), which improved from 2.2% plus or minus 3.1% to 5.7% plus or minus 3.8% (P = .0033) over the 6 months of rosuvastatin therapy. A normal level of FMD would be 8%.

The Hungarian researcher said she and her colleagues wanted to find out whether statin therapy improved the endothelial and macrovascular function as well as arterial stiffness. "These patients had systemic sclerosis with continuous progression for which we don’t even have basic therapy or so-called disease-modifying therapy. We need to try everything to see if something works or not," said Dr. Szucs, the principal investigator.

"Endothelial dysfunction is one of the first steps in the pathogenesis of the disease. If we can improve this step, it is possible that we can slow disease progression, but if this is allowed to worsen then vascular complications lead to clinical symptoms."

All 28 patients who entered the case series study had SSc, according to American College of Rheumatology criteria. The majority (25/28) were female, and average disease duration was just over 13 years. The limited form of SSc, which is most common in females, was present in 21 patients, and 7 had the cutaneous form. Patients included had not received any statin medication for 6 months prior to the study. All patients received 20 mg of rosuvastatin daily for the 6 months of the case-series study.

Other therapies used by patients, and on which they were stable at entry to the study, included ARB/ACE inhibitors (75%), calcium channel blockers (57%), and pentoxifylline (82%).

Vascular and laboratory parameters were checked both before and after rosuvastatin therapy, including triglycerides, total and low-density lipoprotein (LDL) cholesterol, and C-reactive protein (CRP) levels.

Notably, brachial artery flow-mediated dilatation significantly improved in 23 of the total of 28 patients (82%). "For stiffness in the larger arteries [pulse-wave velocity of the aorto-femoral and carotid-femoral] we didn’t see any changes but this might vary if treatment continues for longer. We intend to follow these patients up at 12 months and thereafter."

She added that CRP levels were also shown to improve. CRP levels dropped from 5.1 plus or minus 5.2 mg/L before treatment to 3.4 plus or minus 2.7 mg/L (P = .01) after 6 months. "They are almost in the normal range, but it is better for the patient to have a lower CRP because later cardiovascular morbidity and mortality can decrease."

As expected, LDL levels decreased over the 6 months from 3.0 plus or minus 1.3 mmol/L to 2.2 plus or minus 1.0 mmol/L (P = .005), and mean triglyceride levels dropped from 1.7 plus or minus 0.97 mmol/L to 1.3 plus or minus 0.46 mmol/L (P = .0004).

No difference was seen between the limited form or the diffuse cutaneous form, reported Dr. Szucs.

"Systemic sclerosis is basically a vascular disease and rosuvastatin may improve endothelial dysfunction, correct dyslipidemia, and decrease CRP levels," said Dr. Szucs. "These results suggest that statins should be used together with more conventional vasodilator therapy throughout the disease course in order to protect from micro- and macrovascular damage and complications in scleroderma."

Dr. Szucs has declared no relevant conflicts of interest.