Psoriasis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

GLASGOW, SCOTLAND – The presence of specific autoantibodies may help to predict which patients with systemic sclerosis are likely to develop cancer within a few years of their diagnosis, according to the findings of a U.K.-based registry study.

Development of malignancy within 3 years of a diagnosis of scleroderma was positively correlated with the presence of antinuclear antibodies (ANA) directed against RNA polymerase (RNAP) III in more than half (55.3%) of the patients studied (n = 154).

Anticentromere antibodies (ACA) were found in almost a quarter (23.4%) of patients, and 13.6% had antitopoisomerase I (ATA) or anti-Scl70 (antibodies).

Furthermore, patients with anti-RNAP III antibodies had an almost threefold increased risk of cancer compared with patients with ACA (hazard ratio [HR] 2.907; 95% confidence interval [CI] 1.69-4.99, P less than .0001).

"We think that patients who develop scleroderma and cancer can be divided into two different groups," trainee dermatologist Dr. Pia Moinzadeh of the University of Cologne, Germany, said at the annual meeting of the British Society for Rheumatology.

"The first group are those who develop scleroderma and cancer in a very close temporal relationship, and we saw that these patients are most frequently anti-RNA polymerase positive. So scleroderma in these patients can be considered a paraneoplastic disease."

The other group includes patients who develop cancer after a delay of several years from the onset of systemic sclerosis.

Several epidemiological studies have shown an increased risk of malignancy in patients with systemic sclerosis compared with the general population (Br. J. Dermatol. 2010;163:800-6), Dr. Moinzadeh observed.

This includes increases in breast, lung, and hematologic malignancies (Ann. Rheum. Dis. 2003;62:728-31) in 3%-11% of scleroderma cases (South. Med. J. 2008;101:59-62).

"Late onset of scleroderma has been recognized as a significant risk factor for malignancies, and recent reports have also shown a close and, at times, concurrent onset of scleroderma and cancer," Dr. Moinzadeh added (Clin. Rheumatol. 2004;23:516-22; Curr. Opin. Rheumatol. 2011;23:530-5).

The aim of the current study (Rheumatology 2012;51:[suppl. 3]abstract O42) was to determine the risk of cancer and its association with autoantibodies in a large U.K. cohort. Dr. Moinzadeh performed the research while working at the Royal Free Hospital in London with Dr. Voon Ong and colleagues.

Of 2,177 patients with systemic sclerosis, 154 (7.1%) had a history of cancer. The majority (85.1%) of the patients who developed malignancy were female with a median age of 53 years. Almost two-thirds (63.3%) of the patients had limited disease, and 34.4% had diffuse systemic sclerosis. Anti-RNAP, ACA, and Scl70 were detected in 26.6%, 26%, and 18.2% of patients, respectively.

The most common type of cancer was breast cancer (42%), followed by hematologic malignancies (12%), gastrointestinal tumors (11%), gynecologic cancers (11%), and lung cancer (10.4%).

"We found no differences in gender, age, and disease subsets between patients with and without cancer," Dr. Moinzadeh said.

"When we looked closer at the autoantibody subgroups we saw that the overall frequency to develop cancer was significantly higher in the group of patients who were positive for anti-RNA polymerase antibodies compared with the ones which had anticentromere antibodies."

Differences were seen in the frequency of autoantibodies by tumor type. For example, a higher frequency of anti-RNAP antibodies than the other autoantibodies was seen in breast cancer patients, Scl70 was associated with lung cancer, and ACA with gastrointestinal tumors.

While further research is needed to confirm whether anti-RNAP antibodies could be a marker for early cancer in patients with scleroderma, Dr. Moinzadeh noted there were several "red flags" that could perhaps signal if patients were likely to have "paraneoplastic scleroderma."

These red flags included older age (older than 65 years) of scleroderma onset, male gender, contractural arthropathy or palmar fibrosis, lack of ANA antibodies, and no sign of Raynaud’s phenomenon.

"This is a retrospective study, so we are going to do a prospective study in collaboration with Johns Hopkins University School of Medicine," said coinvestigator Dr. Voon Ong, a consultant rheumatologist at the Royal Free Hospital. The collaboration is necessary given that scleroderma is rare, regardless of its association with cancer.

Dr. Moinzadeh and Dr. Ong reported that they had no financial disclosures.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Urine analysis might help to predict if patients with rheumatoid arthritis are likely to respond to biologic treatments, the results of a small metabolomics study suggest.

Pretreatment levels of histamine, glutamine, xanthurenic acid, and ethanolamine were consistently correlated to response to anti–tumor necrosis factor–alpha (anti-TNF-alpha) therapy at 12 weeks in the 36-patient evaluation.

Further research is needed, of course, before any practical application of the research can be confirmed, but the finding does raise the possibly that a simple urine-based dipstick test could one day be available in the physician’s office.

"TNF has huge effects on metabolism," said Dr. Sabrina Kapoor at the annual meeting of the British Society for Rheumatology. These include effects on rheumatoid cachexia, angiogenesis, the acute phase response, and the recruitment of leukocytes to sites of inflammation.

"Metabolomics assess many metabolites together in biological samples, such as urine or blood," explained Dr. Kapoor, an Arthritis U.K. clinical research fellow in the Rheumatology Research Group at the University of Birmingham (England). The questions were, could such metabolites be found in the urine of patients with arthritic disease, and if they were present, did the metabolites change in response to treatment?

Dr. Kapoor and her associates obtained frozen urine samples from 16 patients with RA and 20 with psoriatic arthritis (PsA).

The samples had been taken during a randomized, three-center clinical study investigating patient responses to treatment with infliximab or etanercept (Rheumatology 2012;51[suppl.3]:abstract O15).

Nuclear magnetic resonance (NMR) spectroscopy was used to analyze the metabolomic profiles of the urine samples that were taken before and 12 weeks after anti-TNF treatment.

All patients in the study received methotrexate and had a disease duration of more than 6 months. RA patients were rheumatoid factor (RF) positive, anti–cyclic citrullinated protein (CCP) antibody positive, or both, and had a DAS28 (Disease Activity Score based on a 28-joint count) greater than 4. PsA patients were negative for RF and anti-CCP antibodies, with three or more swollen or tender joints.

Only the samples from the patients with RA could be linked to treatment effect. All the patients with PsA had a good response to treatment according to EULAR criteria (defined as improvement in two or more of the following: tender joint score, swollen joint score, patient global score, and physician global score).

Changes in the DAS28 were used to identify patients with RA who did (n = 7) or did not (n = 9) respond to anti-TNF therapy at 12 weeks. Good responders were those who achieved a DAS28 lower than 3.2, or an improvement in score greater than 1.2.

The baseline clinical characteristics of "good responders" and "not good responders" were similar: The mean age was about 50 years, all patients were women, and all had a similar history of steroid or nonsteroidal anti-inflammatory drug use.

RA patients who responded well to anti-TNF therapy had a distinct metabolomic profile compared with those who did not exhibit a good response to treatment.

"There was a significant [P = .04] correlation between baseline metabolomic profiles in the urine samples and the extent of change in DAS28," Dr. Kapoor said.

Baseline metabolomic analysis of the urine in RA patients had 85.9% sensitivity and 85.7%, specificity to detect treatment response.

"Urine is actually a cleaner biofluid than other biofluids, such as serum," Dr. Kapoor noted in the discussion that followed her presentation, noting that there are fewer proteins involved that could interfere with the NMR.

The samples tested were randomly obtained, but there is no evidence that any special collection protocols (such as early-morning collection or dietary restrictions) would be needed, she said. There is also no suggestion that urine would need handling in a particular way, although perhaps antibacterial treatment might be needed to keep specimens fresh.

These data, of course, need to be confirmed in a much larger, independent cohort of patients before any subsequent investigation of specific collection or storage requirements.

Dr. Kapoor had no financial disclosures. Merck sponsored the original study, but the company did not sponsor the metabolomics analysis reported here.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

GLASGOW, SCOTLAND – Patients who smoke are substantially less likely to respond to biologic treatment for rheumatoid arthritis than are those who have never smoked.

The percentage of current smokers who responded to treatment with anti–tumor necrosis factor-alpha (anti-TNF-alpha) drugs at 6 months was just 27%, compared with 90% of never smokers and 63% of ex-smokers in a retrospective study of 359 patients.

Similarly poor response to rituximab was seen in patients who were current smokers, with respective response rates for current, ex-, and never smokers of 20%, 68%, and 98%.

©Sveta Kashkina/iStockphoto.com

A response was defined as a mean change in 28-joint disease activity score (DAS28) of 1.2 or greater, according to the U.K. National Clinical for Health and Clinical of Excellence (NICE) definition.

This begs the controversial question of whether current smokers should be given treatment with biologic agents unless they quit smoking, said Dr. Abdul Khan, a rheumatology specialist trainee at St. George’s Hospital in London, speaking at the annual meeting of the British Society for Rheumatology.

Working with Dr. David L. Scott, Dr. Khan assessed whether two simple pretreatment biomarkers – rheumatoid factor (RF) and smoking status – could help predict the response to biologic therapy for RA (Rheumatology 2012;51:iii41-2, abstract O40). They studied 209 patients treated with anti-TNFs and 150 treated with rituximab. The mean age of patients was 56 years for the anti-TNF treated patients and 61 years for the rituximab group. The mean disease duration was 8 years and 13 years, respectively, and 61% and 53% were RF positive.

Primary outcome assessments included the 6-month change in DAS28 and calculation of NICE responders (DAS28 change greater than or equal to 1.2). Smoking status was assessed as being current, previous, or never. Dr. Khan observed that a more detailed evaluation of smoking history might be warranted in future investigations, such as the calculation of pack years. RF status was determined, and anticitrullinated protein autoantibody (ACPA) positivity was determined for patients receiving rituximab therapy.

The mean change in DAS28 scores after 6 months’ anti-TNF therapy for never smokers was 2.6. For current smokers, the mean change was just 0.9 and for ex-smokers, it was 1.39. Corresponding figures for rituximab were 2.92, 0.63, and 1.49.

RF status predicted responses to rituximab but not to anti-TNFs, with a mean change of 2.14 for RF-positive patients and 0.98 for RF-negative patients treated with rituximab after 6 months.

Combining RF and ACPA status showed significant effects with regards to response to rituximab – 80% of never but only 22% of current smokers responded to treatment at 6 month if they were positive for both RF and ACPA

"Smoking and rheumatoid factor/ACPA status had an additive effect on DAS28 responses," Dr. Khan reported. Of 55 never smokers, 46 were RF/ACPA positive and nine were negative and almost all (98%) were NICE responders, with the mean fall in DAS28 score of 2.77.

Strikingly different results were seen for current smokers, however, with 50% of RF-positive patients responding, compared with 3% of RF-negative patients. Previous smokers showed intermediate response rates between those of current and never smokers.

Aside from the other well-documented health risks of smoking – including an increased risk of cardiovascular and pulmonary complications such as chronic obstructive pulmonary disease and lung cancer – these data suggest that patients with RA would do well to give up smoking if they currently smoke.

Indeed, in a press statement, Dr. Scott, professor of rheumatology at King’s College in London, suggested that "these findings show what a dramatic effect modifying your lifestyle, such as giving up smoking, can have on treatment outcomes."

Dr. Khan noted that they also raise an ethical dilemma for clinicians. "The balance of evidence suggests that biologics are unlikely to be cost effective in RA patients who continue to smoke.

"This observation creates a complex ethical dilemma which needs to be addressed."

Dr. Khan and Dr. Scott had no financial disclosures.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.

NEW YORK – Handy mnemonic devices can help predict vaccine response in patients taking biologics for rheumatoid arthritis, according to Dr. Daniel E. Furst.

Vaccinating patients taking biologic agents for rheumatoid arthritis is tricky. The effects of both the vaccine and biologic can be T-cell dependent or independent, or sometimes both, and when the mechanisms match, the vaccine’s response will likely be attenuated, he said at a rheumatology meeting sponsored by New York University.

Think ‘PITH’ – (Human) Papillomavirus, Influenza A/B, Tetanus, and Hepatitis B – to remember which vaccines have protein-based antigens and are T-cell dependent, said Dr. Furst, a rheumatology professor at the University of California in Los Angeles.

For vaccines that have carbohydrate-based antigens, which are largely T-cell independent (B-cell dependent), remember ‘PHIM’: Pneumococcus, H. influenzae B, Influenza A/B, and Meningococcus.

Biologic agents that affect T-cells include methotrexate, the TNF inhibitors, abatacept, and tocilizumab. As a general rule, biologics that affect T-cells decrease one’s response to T-cell dependent vaccines. For example, etanercept has been shown to decrease by as much as half, as well as delay the response to, the hepatitis B vaccine in both normal controls and patients with RA.

In normal volunteers abatacept blunted the response to tetanus vaccine given 2 weeks later by about 50% and given 8 weeks later by about 20%, compared to normal controls (Arthritis Res. Ther. 2007;9:R38).

Likewise, tocilizumab has been shown to reduce the response to the influenza vaccine by about 15%, according to a study presented at EULAR 2007 in Barcelona.

B-cell dependent vaccine responses are diminished by B-cell directed therapy. For example, the SIERRA study of pneumococcal vaccination in rituximab-treated patients showed that, compared to methotrexate alone, a combination of rituximab plus methotrexate decreased the response to the vaccination at 4 weeks by 30% to 60% (Arthritis Rheum. 2010;62:64-74). "That’s just what we would expect," Dr. Furst noted.

It is important to note that biologics that affect T-cell independent mechanisms (B-cell directed therapy), such as rituximab, will not usually affect T-cell mediated vaccine responses. For example, rituximab does not change the response to tetanus toxoid, said Dr. Furst. Similarly, T-cell dependent biologics will not affect T-cell independent vaccinations, citing as an example the lack of effect of adalimumab on the response to the pneumococcal vaccine, according to a paper presented at EULAR in 2006.

The influenza A/B vaccine is an exception to the rule, because it first requires an early B-cell response followed by a T-cell response.

Dr. Furst recommends avoiding live attenuated virus vaccines in patients on biologics or immunosuppressive agents. Vaccines that are likely to be affected include those for varicella/zoster, intranasal influenza/H1N1, measles/mumps/rubella (MMR), yellow fever, oral polio, typhoid (Ty21a oral), vaccinia (smallpox), the BCG vaccine for tuberculosis, and rotavirus. Live viruses can result in disseminated disease in such patients, he said. Ideally patients should be immunized with these vaccines as needed before starting a biologic or any other immunosuppressive therapy.

Dr. Furst is the recipient of research funding/consultant/advisory board member of Abbott Laboratories, Actelion Pharmaceuticals, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor Ortho Biotech, CORRONA, Gilead Sciences, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, Roche Pharmaceuticals/Genentech, and UCB.