CCR 11

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – The proteasome inhibitor bortezomib depletes long-lived plasma cells and thus appears to have great potential as an effective treatment for lupus, Dr. R. John Looney said at the Congress of Clinical Rheumatology.

Bortezomib (Velcade) is approved for the treatment of multiple myeloma and mantle cell lymphoma, and in fact has become a very important drug for these conditions. This "real breakthrough drug" has extensive activity against long-lived plasma cells, which in systemic lupus erythematosus – as in myelomas – are believed to produce harmful antibodies, are extremely resistant to existing therapies, and are associated with refractory disease.

The drug has been shown in some "very, very positive" mouse models to protect against nephritis in lupus-like disease, and recent case reports suggest it might do the same in humans, said Dr. Looney, professor of medicine at the University of Rochester, New York.

The cases, which were presented at the 2010 annual European Congress of Rheumatology, demonstrated that intravenous treatment with 1.3 mg/m² body surface daily at day 1, 4, and 8, together with 20 mg of dexamethasone orally and repeated 1-2 times at 21-day intervals, was associated with marked improvements in refractory lupus nephritis patients, he said.

Urine sediments in both patients were inactive at 6 weeks and proteinuria had markedly decreased, reaching normal in one of the patients at 4 months. Furthermore, anti-dsDNA antibodies had markedly decreased within 4 weeks.

The treatment was associated with some minor toxicities. One patient had myalgias, fever, and headache. Also, antibodies to hepatitis B surface antigen and tetanus toxoid decreased, but protective levels were maintained nonetheless.

Providing additional evidence of a potential role for this drug for protecting against renal damage in lupus, studies suggest it is also useful as an antirejection drug in the setting of renal transplant, Dr. Looney said.

Bortezomib has been shown to directly target long-lived plasma cells producing antihuman leukocyte antigen antibodies. Treatment depletes the plasma cells and achieves dramatic reductions in the anti-HLA antibody levels, thereby improving allograft function.

In addition to the interest in the transplant field for using bortezomib as an antirejection drug, it is also likely that this type of drug – a proteasome inhibitor that targets plasma cells – will be among the new agents available for lupus in the coming years, he said.

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – A finding that the response to etanercept is markedly better than the response to sulfasalazine among patients with ankylosing spondylitis is one of a number of recent developments regarding the treatment of the disease, Dr. Robert Inman said at the Congress of Clinical Rheumatology.

Among other developments Dr. Inman discussed were new findings regarding predictors of response to treatment, the effects of switching biologics, the effects of discontinuing biologics, and the use of newer biologics for ankylosing spondylitis (AS).

The etanercept findings are from the recently published 48-week randomized controlled ESTHER trial (Effects of etanercept versus sulfasalazine in early axial spondlyoarthritis on active inflammatory lesions as detected by whole-body MRI).

The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 20% improvement, 40% improvement, or partial response based on Assessment in SpondyloArthritis International Society (ASAS) criteria were 85% vs. 42% (ASAS20), 70% vs. 31% (ASAS40), and 50% vs. 19% (ASASpR), respectively. The percentage of patients in the etanercept vs. sulfasalazine groups who achieved 50% improvement on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) were 65% vs. 28% (Ann. Rheum. Dis. 2011;70:590-6).

"Etanercept far outperformed sulfasalazine," said Dr. Inman, professor of medicine at Toronto Western Hospital.

Another study, published online in March in Annals of the Rheumatic Diseases, showed that clinical predictors of response to treatment in AS patients include age, presence or absence of human leukocyte antigen B27 subtype (HLA-B27), Bath Ankylosing Spondylitis Functional Index (BASFI) score, and the presence or absence of enthesitis (Ann. Rheum. Dis. 2011;70:973-81).

"This is just clinical bedside analysis," he said, noting that the findings suggest that an ideal patient for treatment would be a young patient with no enthesitis who is B27 positive and who has a low BASFI. The response rate in such a patient, based on the data, would be well over 80%, but that’s not to say patients without all of these characteristics will not respond.

"We’ve certainly had patients (outside of this ideal group) who have had a great response," he said.

As for switching and discontinuing biologics, one study reported at the American College of Rheumatology meeting in 2009 (ACR 2009), which assessed outcomes in patients who switched to a second tumor necrosis factor (TNF) inhibitor after failing the first, showed that switchers achieved a reasonable response. Switchers achieved more than half the response rate (about 30%) of that achieved by nonswitchers (49%), but the percentage of patients achieving ASAS20 on the second anti-TNF (52% of nonswitchers and 44% of switchers) was "actually not bad ... so there’s certainly grounds for switching," Dr. Inman said, noting that there are enough data in the literature to support that.

Another study reported at ACR 2010 showed that infliximab had continued efficacy in HLA-B27 patients with very early AS even after discontinuation before 16 weeks. About 40% of patients treated with infliximab did not flare through week 40 following drug withdrawal.

"So there may be a subset of patients who, if you capture control very early on, you might be able to switch," he said.

Several recent studies also have assessed newer biologics for the treatment of AS – with mixed results.

In a disappointing open-label 24-week study of abatacept reported at EULAR 2010, for example, the ASAS20, ASAS40, ASASpR, and BASDAI50 responses in 15 anti-TNF naive patients were 26.7%, 13.3%, 6.7% and 6.7%, respectively. The only response seen among 15 patients who failed a prior anti-TNF was on the ASAS20, with 20% of patients responding at this level.

"So abatacept does not have a very encouraging signal in ankylosing spondylitis," Dr. Inman said.

Rituximab, however, was shown in a study presented at EULAR 2009 to be associated with good responses at week 24 of treatment. ASAS20, ASAS40 and BASDAI50 response rates were 50%, 40%, and 50%, respectively in anti-TNF treatment naive patients, and 30%, 10%, and 0%, respectively, in those who failed a prior anti-TNF drug.

While these response rates aren’t quite as good as those seen with anti-TNFs, they are fairly good, and suggest that rituximab is a reasonable choice, particularly in patients with a relative contraindication to an anti-TNF, he said.

However, in a patient who has failed an anti-TNF drug, it’s "very unlikely you’re going to hit a home run with rituximab," he added.

Another agent – the anti-IL17A monoclonal antibody secukinumab (AIN57) – was shown in a proof-of-concept study presented at ACR 2010 to be associated with substantially greater ASAS20 response in 30 patients with active AS, compared with placebo (60% vs. 17%). Responses were seen within 1 week in most of the patients.

However, while the response rate was significantly higher than with placebo, the relative change in BASDAI50 was relatively modest and not of the same magnitude typically seen with anti-TNF drugs, he said.

"So I think the jury is still out on the anti-IL17," he concluded.

Dr. Inman disclosed that he is a consultant for Abbott Laboratories, Merck , Pfizer, and Sanofi-Aventis.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Rituximab has a place in the treatment of certain subsets of patients with lupus, but generally the biologic agent has proved disappointing for this disease, according to Dr. R. John Looney.

The chimeric monoclonal antibody against the protein CD20 has worked very well in certain autoimmune diseases, and it is approved for a number of indications including refractory rheumatoid arthritis and antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis.

Rituximab is commonly used in relapsing and remitting multiple sclerosis, and early trial data suggest that the agent may have promise in the management of type 1 diabetes, said Dr. Looney, a professor of medicine at the University of Rochester (N.Y.).

In the "amazingly negative" EXPLORER (A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus) trial, however, overall clinical response rates did not differ significantly in rituximab- and placebo-treated nonrenal lupus patients (Arthritis Rheum. 2010;62:222-33).

And in the LUNAR (A Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With ISN/RPS Class III or IV Lupus Nephritis) trial, patients with lupus nephritis who were treated with rituximab had a modest improvement in proteinuria, compared with those who received placebo, but only a small, non–statistically significant improvement in overall renal outcomes of about 11%, compared with those who received placebo, according to data reported at conferences, including the annual conference of the American College of Rheumatology in 2009, Dr. Looney said.

"So rituximab has been a remarkably effective drug in certain types of autoimmune disease, but it has been a relative failure in lupus," he added.

An exception is in patients with antibodies associated with neuromyelitis optica, he said.

Neuromyelitis optica (NMO), which can also present as a primary disease, is remarkably responsive to rituximab, and there is a subset of lupus patients who have the NMO IgG/aquaporin-4 antibody that is associated with the disease, he said.

"If you’re looking at a patient with lupus who develops optic neuritis or if they develop transverse myelitis, you have to think about whether they are in a subgroup with these NMO antibodies," he said, noting that these patients will tend to have longitudinally extensive transverse myelitis that extends over three vertebral bodies, and they will tend to be positive for aquaporin-4.

"In this subgroup, we have moved to using rituximab early in the course of disease if [these patients] have been very refractory to other treatments," he said.

Dr. Looney said he also continues to use rituximab in severe refractory systemic lupus erythematosus, particularly in patients with central nervous system disease or lupus nephritis, as well as in patients with refractory idiopathic thrombocytopenic purpura (ITP).

Although rituximab is not approved for ITP, it is widely used as a secondary therapy for this condition, he said.

Dr. Looney disclosed that he has been an advisor for Genentech.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug's efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud's phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – Bosentan, which has been shown to prevent digital ulcers in systemic sclerosis, also may have beneficial effects on skin fibrosis.

In a small, prospective, open-label study, treatment with the dual endothelin receptor antagonist was associated with a significant reduction in skin thickening as measured by the modified Rodnan skin score (mRSS), Dr. Annegret Kuhn said at the Congress of Clinical Rheumatology.

The mean change from baseline in the mRSS in the 10 systemic sclerosis patients in the study was 6.4 points on the 0-51 point scale, said Dr. Kuhn of Westfälische Wilhelms-Universität Münster (Germany).

Significant responses were seen in patients with both diffuse and limited disease, and there also was significant healing of digital ulcers. No differences were seen from baseline and week 24, however, on 20-MHz ultrasound, fist-closure evaluation, U.K. systemic sclerosis functional score, or the modified sclerosis health assessment questionnaire (SHAQ) and its visual analogue scale (Rheumatology [Oxford] 2010;49:1336-45).

Patients were treated with 62.5 mg of bosentan twice daily for 4 weeks, then with 125 mg twice daily for 20 weeks. This regimen is similar to the dosing used in the RAPIDS-1 and -2 (Randomized Placebo-Controlled Study on Prevention of Ischemic Digital Ulcers in Systemic Scleroderma–1 and –2) trials, which demonstrated the drug’s efficacy for the prevention of digital ulcers. Bosentan is currently approved for use in the United States for pulmonary artery hypertension, and – based on the RAPIDS-1 trial (Arthritis Rheum. 2004;50:3985-93) – it was also approved in Europe in 2007 for prevention of digital ulcers.

The RAPIDS-2 trial that was published this year (Ann. Rheum. Dis. 2011;70:32-8), included treatment for at least 24 weeks, and confirmed the preventive effects seen in RAPIDS-1. Bosentan was not found in either trial to be associated with improved healing in existing ulcers, however.

"Iloprost remains the best treatment for digital ulcers in systemic scleroderma," Dr. Kuhn said,

But bosentan is recommended for prevention, and it may also improve fibrosis, she noted.

Guidelines that were developed this year by a group of German experts on scleroderma call for first-line treatment with iloprost for the healing of existing ulcers, with repeated infusions for long-term care. They also call for the use of bosentan for prevention, and note that current experimental treatments include sildenafil and atorvastatin, she said.

Treatment of underlying disease (such as Raynaud’s phenomenon, vasculopathy, and the like) is also important, as are general preventive measures including nicotine abstinence, cold protection, physical treatments, lymphatic draining, elimination of sympathomimetics, and vasoconstrictors.

Topical treatments can include antiseptic agents, becaplermin gel, hydrocolloid membrane, topical lidocaine, and vitamin E gel, according to the guidelines.

Dr. Kuhn had no disclosures to report.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.

DESTIN, FLA. – For now, the lupus patients most likely to respond to recently approved belimumab may be those with moderate to severe disease without renal or central nervous system involvement who have failed to respond to standard therapy, according to Dr. R. John Looney.

More specific details on which patients are most likely to benefit will require further experience with the drug, he said at the Congress of Clinical Rheumatology.

Belimumab (Benlysta), which was approved in March, is the first new drug for systemic lupus erythematosus (SLE) in 50 years. It has a very good safety profile, although the effect size, while statistically significant, is relatively small, with only an average of about a 12 percentage point difference in the response rates between treatment and placebo in trials of the fully human monoclonal antibody that inhibits B-lymphocyte stimulator, said Dr. Looney, professor of medicine at the University of Rochester (N.Y.).

Still, that reflects improvement of about 25%-30%, he noted.

The standard dosage is 10 mg/kg, given intravenously every 2 weeks for three times, then every 4 weeks, in addition to standard care.

Keep in mind that the onset is somewhat slow, so this "may not be a drug you would use in a flaring patient," Dr. Looney said.

Also, it has not been studied in severe renal or central nervous system disease, nor in combination with cyclophosphamide, he noted.

Furthermore, no particular subgroup has yet been identified in whom the drug has particular benefits, so it is a bit of a challenge to determine who should be put on this drug.

"I would consider it in patients with moderate to severe, nonrenal, nonneurologic disease who have failed standard therapy," Dr. Looney said, explaining that he would consider those to be patients with continued disease activity or patients in whom steroids can’t be tapered or stopped despite treatment.

"So I look at this as a drug that might help me get my patients who are on hydroxychloroquine and let’s say CellCept [mycophenolate] or Imuran [azathioprine], down to a manageable dose of steroids," he added.

Determining how long to treat, however, is a challenge.

"We have no good way to look at an individual patient and say they are better and they are better because they are on belimumab," Dr. Looney said, noting that based on belimumab trial data, three out of four patients who were responders at 1 year would have been responders on placebo, so further study is needed to help guide treatment duration.

"I would also really like to see predictors of response," he said, noting that such predictors have thus far not been reported.

Further analysis of existing data may be useful for identifying subgroups who will respond best to belimumab. Additional studies in renal and CNS disease would also be useful.

"It may be that you add this drug to current therapies [in renal and CNS patients] and they do that much better," Dr. Looney said, noting that it would also be useful to look at belimumab treatment in conjunction with cyclophosphamide and rituximab as well "to see what happens when B cells are targeted in two different ways."

Dr. Looney disclosed that he has been an adviser for Genentech.