EULAR (European League Against Rheumatism): 2012 Congress

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – If at first you don’t succeed in getting satisfactory results when prescribing a tumor necrosis factor inhibitor in ankylosing spondylitis, don’t hesitate to switch to another. And, if need be, switch again. And again.

"Irrespective of the reason for discontinuation of the first [tumor necrosis factor (TNF)] inhibitor, switching to another TNF inhibitor should be considered," said Dr. Bente Glintborg of Gentofte University Hospital, Copenhagen, at the annual European Congress of Rheumatology.

That’s her key message gleaned from DANBIO, the Danish national registry of patients on biologic agents for rheumatic diseases. DANBIO is a comprehensive registry reflecting real-world clinical practice. Physician reporting to the registry is mandatory, with no informed consent requirement.

Dr. Glintborg reported on 1,436 ankylosing spondylitis (AS) patients followed for a median of 2.4 years after going on their first TNF inhibitor and enrolling in DANBIO.

The first key lesson from DANBIO is that switching anti-TNF biologics in patients with AS is common. Of DANBIO participants, 30% switched to a different TNF inhibitor. Changes made due to lack of efficacy outnumbered those due to adverse events by 2 to 1.

A total of 137 patients, or 10% of the original cohort, switched again to a third TNF inhibitor. This time around, changes made because of lack of efficacy outpaced those due to adverse events by 3 to 1. Thirty-nine patients went on to switch to a fourth TNF inhibitor.

Switchers were disproportionately female, and had an average disease duration several years less briefer than that of nonswitchers. They also had greater baseline disease activity by a variety of measures.

Each successive switch to a different TNF inhibitor brought a yet-lower favorable clinical response rate. Nevertheless, 2 years after embarking on anti-TNF therapy, 52% of switchers enjoyed a good clinical response as defined by at least a 50% decrease from baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI), as did 63% of nonswitchers. The number needed to treat in order to obtain a good clinical response was 1.6 among nonswitchers and 1.9 for switchers.

The favorable clinical response rate after 6 months on a TNF inhibitor was 59% during the first treatment course, 41% during the second, and 32% with the third. The number needed to treat was 1.7, 2.4, and 3.0, respectively, she reported.

The median duration on first-line anti-TNF therapy was 3.1 years, falling to 1.6 years for a second course and 1.8 years with a third.

Male gender and a low baseline BASFI were significant predictors of longer adherence to the second TNF inhibitor prescribed. Among the many factors that proved unrelated to adherence were the specific anti-TNF agent, baseline C-reactive protein level, presence or absence of concomitant methotrexate, and the reason for stopping the first TNF inhibitor.

Infliximab (Remicade) was the most frequently prescribed first-line agent among Danish AS patients. A total of 45% of patients received it. The next most popular first-line TNF inhibitors were adalimumab (Humira), given to 37%, and etanercept (Enbrel), at 16%. Adalimumab was the second-line agent selected in 46% of first-time switchers, followed by etanercept in 40% and infliximab in 10%.

Session cochair Dr. Martin Rudwaleit expressed appreciation for the Danish effort to shed light on the sequential use of TNF inhibitors in AS, a heretofore understudied subject.

"I think it’s very good news to hear that switching can be quite effective, as you have shown in this open registry, particularly in light of not having any other compounds available at the moment to give to these patients," commented Dr. Rudwaleit of Charité University Hospital, Berlin.

Dr. Glintborg reported having no financial conflicts.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

BERLIN – Ankylosing spondylitis patients are at sharply increased risk of various forms of acute and chronic renal comorbidity, according to the first population-based study to examine the issue.

The explanation for this elevated renal risk is likely twofold: the well-documented nephrotoxic effects of long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs), the first-line treatment mainstay in ankylosing spondylitis (AS); and extra-articular manifestations of the disease process itself, according to Adrian R. Levy, Ph.D., of the research firm Oxford Outcomes in Vancouver, B.C.

He presented a retrospective cohort study utilizing Quebec’s administrative physician-billing database. He identified 8,616 individuals with AS in the Canadian province during 1996-2006, and determined their rate of diagnosed renal comorbidities. Then he compared the AS group to a randomly generated sample of 1% of the general Quebec population without AS.

Overall, diagnosed renal complications were present in 3.4% of men and 2.1% of women with AS, compared with 2% and 1.6%, respectively, in the general population. Age- and gender-adjusted prevalence ratios demonstrated significantly excess risks of various forms of renal disease in the AS population, Dr. Levy said at the annual European Congress of Rheumatology.

The magnitude of the increased risk was greatest in younger patients with AS. For example, the prevalence ratio for any of the renal conditions under study was 2.4-fold greater among 20- to 39-year-old men with AS than controls, but only 1.5-fold greater in AS patients over age 60.

The clinical implications are clear, Dr. Levy emphasized: Close and careful monitoring for renal complications is de rigueur in individuals with AS, especially if they are on long-term, full-dose, continuous NSAID therapy.

The study was funded by Abbott.

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.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

UPDATED: 06/21/2012

BERLIN – If the Food and Drug Administration follows the advice of its Arthritis Advisory Committee and approves tofacitinib as a new drug for treating rheumatoid arthritis later this summer, the oral, small-molecule drug may start to muscle in on the treatment turf now occupied by antitumor necrosis factor drugs, some experts predicted at the Annual European Congress of Rheumatology.

The attraction would be the good efficacy tofacitinib has shown in five phase III trials, a decent safety profile that looks on par with antitumor necrosis factor (TNF) drugs, and delivery as a twice-daily oral pill, a property that will give tofacitinib an edge over the anti-TNFs and other biologics that require injection or infusion.

"The fact that [tofacitinib] is oral is something of an advantage, so there will be a role for it, and it makes sense therapeutically," Dr. Joel M. Kremer said at the meeting. "But we will need to be smart" on using tofacitinib and other new drugs from the same class to treat patients with rheumatoid arthritis (RA), and their use relative to methotrexate and the biologics, said Dr. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College.

Another view was that tofacitinib will need to prove its value in larger numbers of patients, and though it will be a welcome new option – first to market from the class of Janus kinase (JAK) inhibitors – it will take its initial place post approval behind the anti-TNFs, which have more than a decade’s track record, said Dr. Iain B. McInnes in a separate talk at the meeting. Many rheumatologists "feel they will kick in after a first biologic treatment," which itself comes after first-line methotrexate, said Dr. McInnes, a rheumatologist and professor and Muirhead Chair of Medicine at the University of Glasgow, Scotland.

"The efficacy we’ve seen [from tofacitinib and other JAK inhibitors] is very encouraging, but safety will be a major driver of clinical decisions and [will] influence the order of choice. If a patient does not get an adequate response from methotrexate after 3-6 months, I would add a biologic drug, especially an anti-TNF. Inevitably, there will be less safety assurance with the new drugs. The current role for JAK inhibitors is closer to the options like abatacept, rituximab, and tocilizumab, but I think that may change" once JAK inhibitors enter routine practice, Dr. McInnes said in his talk.

"I have a lot of experience with tofacitinib, and I’m very comfortable with it; if a patient wanted this drug, I would use it," said Dr. Roy Fleischmann, who led phase II and phase III trials with tofacitinib and is codirector of rheumatology at Texas Health Presbyterian Medical Center in Dallas.

"What will practicing rheumatologists with no experience with the drug do? We’ll see what the FDA says. They might use it after methotrexate, because the data are strong. It will be up to patients: an oral drug or an injected one."

Pfizer, the company developing tofacitinib, reported data from five phase III trials and safety experience in about 4,800 patients to the FDA Advisory Committee in May. And four of the five trials examined use of the drug in RA patients as monotherapy; in combination with methotrexate; in combination with background methotrexate in patients who failed to respond to an anti-TNF drug; and in combination with a background disease modifying antirheumatic drug. The fifth study, a 2-year trial that so far has reported results from an interim, 1-year analysis only, examined tofacitinib’s ability when used in combination with methotrexate to stop radiographic progression of joint damage, compared with methotrexate alone.

Results from across the studies showed consistent efficacy, including inhibition of radiographic progression that significantly surpassed placebo patients, and a "consistent side effect profile," Dr. Kremer said. "I consider it on the same shelf for potential infections and adverse events as the [already approved] biologics," he said in an interview. He said he would shy away from prescribing tofacitinib, or any biologic, to patients who get frequent pneumonia, cellulitis, or other infections.

Perceived safety will likely be the major driver – or impediment – for use of tofacitinib during the first year or 2 after its approval, predicted Madhuri Borde, Ph.D., director of the immune and inflammatory disorders group of Decision Resources, a pharmaceutical-market consulting company in Burlington, Mass. In mid-May, Dr. Borde presented 52 U.S. rheumatologists with active RA practices the same tofacitinib data that the FDA Advisory Committee saw and she asked the rheumatologists what they thought of the drug and how they might use it soon after it hit the U.S. market.*

The results showed that rheumatologists were impressed by the efficacy results, saw safety as being similar to anti-TNF drugs, and mostly saw tofacitinib currently as a drug they would use when RA patients don’t respond to an anti-TNF agent. "For physicians, it boils down to their comfort with the safety profile," she said in an interview, and they think safety is still a little uncertain.

Although Dr. Borde conceded that "patients are wary of injections" and that oral dosing is an attractive option for many patients, physician uncertainty about safety will generally trump that. "I think safety concerns will drive caution in using tofacitinib," at least during the first couple of years on the market, until a higher comfort level is reached. It’s likely that in an effort to stimulate interest in the drug, Pfizer will price it aggressively, at a small but significant discount to anti-TNF drugs. But even a cost savings probably won’t be enough early on to knock the anti-TNFs from their established RA perch, she said.

Dr. Kremer said that he has received research support from and has been a consultant to Pfizer and several other drugs companies. Dr. McInnes said that he has received research support from and has been a consultant to and speaker for Pfizer and several other drug companies. Dr. Fleischmann said that he has received research support from and has been a consultant to Pfizer and several other drug companies. Dr. Borde said that she had no disclosures.

*New information about Dr. Borde's title has been added to this story.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

BERLIN – Prescribing hydroxychloroquine for the treatment of rheumatoid arthritis may reduce a patient’s risk of developing type 2 diabetes by more than 40%.

That’s the provocative implication of a longitudinal prospective observational study of 10,583 American patients with rheumatologist-diagnosed rheumatoid arthritis (RA) followed from 2000 through 2010. It’s a clinically important observation in light of the impact of diabetes on cardiovascular risk, Dr. Marie Holmqvist said at the annual European Congress of Rheumatology.

Findings from other, smaller studies also have shown the potential benefit of hydroxychloroquine in lowering the risk of diabetes in RA patients, but none was as large as this one (J. Clin. Rheumatol. 2011;17:115-20; JAMA 2007;298:187-93). The association has led some investigators to dub hydroxychloroquine "a diabetes drug in disguise" (BMJ Case Rep. 2009;2009. pii: bcr08.2008.0654).

At baseline, the patients with RA had an average age of 60 years and a mean 13.6-year disease duration. One-quarter of them were on hydroxychloroquine as mono- or combination therapy, 30% were on methotrexate with or without a tumor necrosis factor (TNF) inhibitor, and 42% were on other or no disease-modifying antirheumatic drugs (DMARDs).

During follow-up, 6.4% of subjects were diagnosed with new-onset type 2 diabetes. The incidence was 1.34 cases per 100 person-years. In a multivariate analysis adjusted for RA duration, ethnicity, body mass index, employment status, income, age, gender, comorbidity, and Health Assessment Questionnaire score, hydroxychloroquine use was independently associated with a 41% reduction in the likelihood of developing diabetes compared with Centers for Disease Control and Prevention–generated figures for the matched U.S. population.

Methotrexate with or without a TNF inhibitor was associated with a 20% decrease in the risk of diabetes as long as a patient wasn’t also on prednisone. If the methotrexate regimen included prednisone, the protective effect was lost. In contrast, hydroxychloroquine with prednisone remained protective, with an associated 40% risk reduction.

Prednisone by itself was associated with a 30% increased risk of developing diabetes. Most strikingly, golimumab (Simponi) was associated with a 12.3-fold increased risk. None of the other medications prescribed for RA showed a significant relationship with diabetes risk, reported Dr. Holmqvist of Karolinska University, Stockholm.

Her study was funded by the Karolinska Institute and the U.S. National Data Bank for Rheumatic Diseases. Dr. Holmqvist reported having no financial conflicts.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

BERLIN – Patients with at least three erosive joints in their hands and feet have rheumatoid arthritis regardless of whatever other signs and symptoms they may or may not have, according to a task force of the American College of Rheumatology and the European League Against Rheumatism (Ann. Rheum. Dis. 2012;71[Suppl3]:25).

This unanimous decision from the 18-member international task force closes the circle for redefining the classification of rheumatoid arthritis patients, a process that began with the 2010 release of a new signs and symptoms–driven rheumatoid arthritis (RA) classification that had no role for radiographic evidence of joint erosions (Arthritis Rheum. 2010;62:2569-81).

Although "radiographs are not required in the ACR/EULAR classification criteria, the presence of typical erosions allows classification of RA even without fulfillment of the [2010] scoring system," task force leader Dr. Désirée van der Heijde said at the meeting. "Radiographs should be taken in an unclassified patient in whom long-standing, inactive disease is suspected, and is likely misclassified," said Dr. van der Heijde, professor rheumatology at Leiden (the Netherlands) University Medical Center. Another common scenario is when a radiograph already exists for a patient who might have early arthritis because it was taken before rheumatologic referral.

The key premise of the new erosive-joint classification was that because radiographs alone could classify a patient as having RA, the erosive joint criteria had to be very specific and produce a minimal number of false positives. Lack of sensitivity was not an issue, as patients could also be classified with RA by the 2010 criteria.

To get a sense of how many erosive joints are needed to produce a reliable identification of RA, the task force studied data collected from two early-arthritis groups, the Early Arthritis Cohort assembled in Leiden with 902 patients, and the Etude et Suivi des Polyarthrites Indifferenciées Récentes (ESPOIR) cohort assembled in Montpellier, France with 811 patients. The task force focused on the subgroup of people in either cohort who did not meet the 2010 classification criteria for RA, and examined the link between various numbers of erosive joints in these people and the incidence of three outcomes the task force considered pathognomonic for RA: on methotrexate treatment after 1 year, on treatment with any disease-modifying antirheumatic drug after 1 year, or disease persistence for 5 years. They found that all three outcomes occurred at similar rates.

In the ESPOIR cohort, with the end point of 5-year disease persistence, people with at least three erosive joints developed RA with a specificity of 91% and a sensitivity of 24%. (An erosive joint was any hand or foot joint with at least one radiographic erosion visible as a cortical break.) In contrast, a threshold of at least two erosive joints carried a specificity of 82% – putting it below the 90% the task force sought – and a sensitivity of 30%. In the Leiden cohort, three or more erosive joints had a sensitivity of 95% and a sensitivity of 15%, while two or more joints was 91% specific and 20% sensitive.

"Some rheumatologists might be surprised [at the need for three erosive joints] because they think that just one erosion is very specific for RA. We showed that one erosion is not specific; you really need more to be very specific for RA," she said in an interview. "After we saw the data it was very clear to us that three would be the right cutoff. It was a unanimous decision."

It also turned out that a criterion of three or more erosive joints kept a lid on the number of positive classifications. In the Leiden cohort, 31 (10%) of the 308 enrollees who did not meet the 2010 clinical criteria met the radiographic threshold; in the ESPOIR cohort, 18 (12%) of 147 had at least three erosive joints.

"There will not be many patients who get classified," based on their erosive joints, she noted. Despite that, "it’s very important to have this definition, because many people were asking for it. It’s important to have a clear definition. And it’s important for patients who do not meet the classification criteria but have several erosions."

"Erosions are the hallmark of RA; if patients have erosions they don’t need anything else," commented Dr. Alan Silman, medical director of Arthritis Research UK in Chesterfield, England. The new findings show "there are very few people with RA who just have erosions. The results support the classification criteria," by showing that the 2010 criteria capture roughly 90% of all RA patients, he said in an interview.

Dr. van der Heijde and Dr. Silman said that they had no disclosures.

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela reported having no financial conflicts.

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela reported having no financial conflicts.

BERLIN – Occupational exposures associated with increased risk of rheumatoid arthritis include jobs involving inhalation of chemicals or dusts as well as work in cold or humid conditions, according to data from a new Scandinavian case-control study.

Dr. Ritta-Sisko Koskela obtained detailed occupational exposure histories from more than 2,000 employed Finnish adults with rheumatoid arthritis (RA) and an equal number of hypertensive controls matched for age, occupation, gender, and region.

The impetus for the study was her observation that the age-adjusted prevalence of RA in Finland shows considerable geographic variation. Some of the highest rates occur in areas where certain industries are concentrated, such as mining, steel manufacturing, chemical processing, and ship dockyards, explained Dr. Koskela of the Finnish Institute of Occupational Health, Helsinki.

A prominent theme that emerged from the data is that occupationally linked RA seems to require a long duration of exposure and entails a lengthy latency period. For example, dock and warehouse workers with RA were 3.1-fold more likely to work under drafty conditions than were hypertensive dock workers without RA. The individuals with RA had a mean 15 years of exposure to drafty conditions, and they developed the disease an average of 20 years after this workplace exposure began.

And those were among the shortest exposure and latency times recorded in the entire study. For instance, chemical plant workers with RA were 6.9-fold more likely to have been working under cold conditions than were their coworkers without RA; they averaged a 26-year exposure history and a 29-year latency period. And metal workers with RA were 10.4-fold more likely to work with rubber and elastomers than were metal workers without RA; the workers with RA had an 18-year history of exposure to those chemicals and a 23-year latency phase, she said at the annual European Congress of Rheumatology.

Truckers with RA were 5.7- to 8.3-fold more likely to haul grain, concrete, or gas mixtures than were truckers without RA. And textile workers with RA were 8.7 times more likely to labor under humid conditions than were those without the disease. Farmers and foresters with RA were 2.1-fold more likely to work under high-humidity conditions and 6.1-fold more likely to experience infection by parasites or insect vectors than were those without RA.

Inhaled dusts linked to an increased prevalence of RA included synthetic mineral fibers, concrete, paints, pesticides, and carbonate minerals.

Dr. Koskela’s study builds on an earlier Swedish analysis of a national database including nearly 30,000 Swedes hospitalized for RA. That study identified certain occupations as being associated with increased risk, among them mining, farming, and electrical work, and in women nursing and social work (J. Rheumatol. 2008;35:986-91). The Finnish study takes things a step further by examining specific work-related factors within higher-risk occupations that distinguish those who develop RA from those who don’t. The aim is eventually to reduce the incidence of RA through avoidance of potentially modifiable exposures.

Dr. Koskela 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.