Psoriasis

BUENOS AIRES – The antimalarial drug hydroxychloroquine is now standard first-line therapy in systemic lupus erythematosus, with most SLE patients taking it indefinitely alone or in addition to other medications.

It was not always this way. The past 15 years have seen what was long regarded as a mild drug, one commonly withdrawn after evidence of disease improvement, become more often compared to a miracle drug. Hydroxychloroquine (HCQ) is now considered indispensible in lupus, and is thought to confer a host of previously unrecognized benefits, with new ones being discovered every year.

Prospective and retrospective observational studies have found HCQ use associated with the prevention of lupus flares, less damage accrual, prolonged survival, less vascular damage, fewer thrombolic and cardiovascular events, better renal outcomes, and skin and joint improvement (J. Rheumatol. 2012;39:1769-71). One team of investigators has hypothesized that HCQ decreases cancer risk in people with lupus (Ann. Rheum. Dis. 2007;66:815-17). But other researchers have challenged some of these studies as potentially biased and not in keeping with observed clinical outcomes.

At the international congress on systemic lupus erythematosus, researchers discussed the latest findings related to HCQ in lupus, and shared thoughts on their implications for clinical practice.

Dr. Murray Urowitz, a senior scientist at the Toronto Western Research Institute, referred to results from a large multicenter cohort study (n = 1,631) that showed SLE patients taking antimalarial drugs in the absence of immunosuppressant medicines had significantly lower risk of seizures (Ann. Rheum. Dis. 2012;71:1502-9), possibly because HCQ is protective against flares, and seizures are thought to be caused by active neuropsychiatric lupus.

"We’ve heard this antimalarials story over and over again," Dr. Urowitz said, in commenting on the seizure findings. "Why aren’t all of our patients on antimalarials?"

HCQ use was seen as protective against cardiovascular disease (odds ratio 0.34, 95% confidence interval 0.16-0.71; P = .003) in a cohort of 306 SLE patients in Turkey, according to findings presented at the conference by Dr. Murat Inanc of Istanbul University (Lupus 2013;22[Suppl.]:O07).

In a separate presentation, Dr. Jill Buyon, director of the Lupus Center at New York University, reported encouraging preliminary data from a small, open-label study (n = 19) of HCQ in pregnant women with anti-SSA/Ro antibodies who previously had a child with cardiac manifestations of neonatal lupus, or cardiac-NL.

The major manifestation of cardiac-NL is heart block, an abnormality in which the heart beats too slowly. It is seen in about 2% of pregnancies in mothers with anti-SSA/Ro and anti-SSB/La serology, and the risk is 17.4% for those who have previously given birth to a child with cardiac-NL. Thus far, third degree heart block has been seen in only 1 of 17 pregnancies in women with a previous child with cardiac-NL taking 400 mg hydroxychloroquine daily, Dr. Buyon reported, suggesting a protective effect.

Dr. Bevra Hahn, chief of rheumatology at UCLA David Geffen School of Medicine, Los Angeles, discussed her own approach to HCQ in the clinic. When faced with patients whose serology or symptoms are suggestive of lupus yet insufficient to fulfill criteria for a lupus diagnosis, Dr. Hahn said she initiates treatment with HCQ. "Can we prevent, delay, or make disease milder with [HCQ]? My answer to that is yes, and we do it a lot," Dr. Hahn said, citing a retrospective study that showed lupus onset to be delayed in people treated with HCQ (Lupus 2007;16:401-9).

Another recent case-control study (n = 481) bolstered the case for early use of HCQ. Investigators found that prompt use of HCQ after SLE diagnosis protected against cumulative damage after 3 years (J. Rheumatol. 2013 April 15 [doi:10.3899/jrheum.120572]).

Dr. Guillermo Ruiz-Irastorza of the University of the Basque Country, Barakaldo, Spain, gave an update at the congress on current approaches to antimalarials. "I am absolutely convinced that HCQ has a very wide range of good effects in lupus, and that the longer it is used, the better it works," he said in a later interview. "Our patients are now almost 100% on HCQ, and the outcome of most of them is amazing – obviously not only because of HCQ, but I am sure it plays a main role. We have seen very severe flares in patients stopping HCQ monotherapy. HCQ is also a crucial part of therapy in renal disease – along with lower prednisone doses, pulse methylprednisolone, and low-dose cyclophosphamide. That is our protocol, with excellent results."

A better understanding of the way HCQ works in lupus has only increased the perception of its clinical importance. In recent years, HCQ was found to have activity against antiphospholipid antibodies (Lupus 2010;19:460-9), which helps to explain its protective effect against pregnancy loss and thrombosis in SLE. More recently, HCQ has been found to antagonize toll-like receptors (TLR) 7 and 9, which are components of innate immunity erroneously activated in lupus. They are a target for new drug development in SLE (Curr. Allergy Asthma Rep. 2012;12:1-7).

Dr. David Pisetsky, professor of immunology at Duke University, Durham, N.C., discussed the implications of HCQ’s anti-TLR activity at the congress. "This relatively benign drug has powerful immunological effects, even though we don’t really think of it that way," he said. "When we’re talking about strategies to block TLR, we’ve already been probably doing it unbeknownst to us rather effectively."

Dr. Buyon, who was moderating Dr. Pisetsky’s talk, noted: "Maybe we’re really underselling ourselves [with HCQ]. Most of us confine ourselves to 6.5 mg/kg," she said, referring to the well-known risk of ocular toxicity and retinal changes associated with long-term HCQ treatment, requiring patients on HCQ to get eye exams yearly. Dr. Pisetsky agreed: "To me it would seem very worthwhile to push the dose to get more out of it."

Dr. Pisetsky and Dr. Buyon both expressed hope that manufacturers would seek to create an HCQ-like compound without the ocular risk, allowing the administration of higher doses with presumably more clinical effect. "But so far there’s been a very limited effort," Dr. Pisetsky said.

Another lupus researcher, rheumatologist and epidemiologist Dr. Sasha Bernatsky of McGill University, Montreal, expressed cautious optimism about some of the recent findings. Like Dr. Urowitz, Dr. Inanc, Dr. Buyon, Dr. Ruiz-Irastorz, and many other international scientists, Dr. Bernatsky is a member of the Systemic Lupus International Collaborating Clinics research group, which studies long-term outcomes in SLE.

"The exact possibilities, in terms of disease modification, remain a matter for further study," Dr. Bernatsky said in an interview, adding that while she strongly endorses HCQ for its many benefits, and recommends the drug in almost all SLE patients, she doesn’t fully understand the extremely strong effects that recent studies have suggested, related to nephritis, central nervous system manifestations, cancer, and overall survival.

Dr. Bernatsky struggles with the findings of a study that found HCQ associated with a 70% reduction in renal damage in lupus patients (Arthritis Rheum. 2009;61:830-9; Arthritis Rheum. 2009;61:1614-5). "I am amazed by that degree of disease-modifying effect in terms of active kidney disease, with [HCQ]," she said.

The recent finding of reduced seizures in lupus patients taking HCQ also surprised her. "A hazards ratio of 0.07 suggests that antimalarials reduce 93% of the risk of seizures, which is an incredibly large effect size."

One area of particular debate in HCQ and lupus concerns cancer risk. While Dr. Ruiz-Irastorza and his colleagues found a protective effect associated with HCQ in a cohort study of 235 patients (Ann. Rheum. Dis. 2007;66:815-7), "I did not believe the results at first," Dr. Ruiz-Irastorza said. "However, after discovering several papers showing biological plausibility for such an effect, I changed my mind. It seems to work by a number of different mechanisms, including inhibition of autophagy and sensitization of tumor cells to chemotherapy."

Dr. Bernatsky and SLICC investigators have studied malignancy risk and medication exposures in a large cohort (n = 16,409) of SLE patients (J. Autoimmun. 2013;42:130-5) without finding a protective effect associated with HCQ. "While I would not rule out some beneficial effects for cancer risk in the rheumatic diseases, I think the jury is still out," she said.

Nonetheless, Dr. Bernatsky said, "At our clinic, we keep most of our patients on antimalarials for years, and I hope it is similar in the United States and Europe. I’m happy for almost all SLE patients to be on HCQ because I think it’s a great drug."

None of the investigators mentioned have financial disclosures related to HCQ.

BUENOS AIRES – The antimalarial drug hydroxychloroquine is now standard first-line therapy in systemic lupus erythematosus, with most SLE patients taking it indefinitely alone or in addition to other medications.

It was not always this way. The past 15 years have seen what was long regarded as a mild drug, one commonly withdrawn after evidence of disease improvement, become more often compared to a miracle drug. Hydroxychloroquine (HCQ) is now considered indispensible in lupus, and is thought to confer a host of previously unrecognized benefits, with new ones being discovered every year.

Prospective and retrospective observational studies have found HCQ use associated with the prevention of lupus flares, less damage accrual, prolonged survival, less vascular damage, fewer thrombolic and cardiovascular events, better renal outcomes, and skin and joint improvement (J. Rheumatol. 2012;39:1769-71). One team of investigators has hypothesized that HCQ decreases cancer risk in people with lupus (Ann. Rheum. Dis. 2007;66:815-17). But other researchers have challenged some of these studies as potentially biased and not in keeping with observed clinical outcomes.

At the international congress on systemic lupus erythematosus, researchers discussed the latest findings related to HCQ in lupus, and shared thoughts on their implications for clinical practice.

Dr. Murray Urowitz, a senior scientist at the Toronto Western Research Institute, referred to results from a large multicenter cohort study (n = 1,631) that showed SLE patients taking antimalarial drugs in the absence of immunosuppressant medicines had significantly lower risk of seizures (Ann. Rheum. Dis. 2012;71:1502-9), possibly because HCQ is protective against flares, and seizures are thought to be caused by active neuropsychiatric lupus.

"We’ve heard this antimalarials story over and over again," Dr. Urowitz said, in commenting on the seizure findings. "Why aren’t all of our patients on antimalarials?"

HCQ use was seen as protective against cardiovascular disease (odds ratio 0.34, 95% confidence interval 0.16-0.71; P = .003) in a cohort of 306 SLE patients in Turkey, according to findings presented at the conference by Dr. Murat Inanc of Istanbul University (Lupus 2013;22[Suppl.]:O07).

In a separate presentation, Dr. Jill Buyon, director of the Lupus Center at New York University, reported encouraging preliminary data from a small, open-label study (n = 19) of HCQ in pregnant women with anti-SSA/Ro antibodies who previously had a child with cardiac manifestations of neonatal lupus, or cardiac-NL.

The major manifestation of cardiac-NL is heart block, an abnormality in which the heart beats too slowly. It is seen in about 2% of pregnancies in mothers with anti-SSA/Ro and anti-SSB/La serology, and the risk is 17.4% for those who have previously given birth to a child with cardiac-NL. Thus far, third degree heart block has been seen in only 1 of 17 pregnancies in women with a previous child with cardiac-NL taking 400 mg hydroxychloroquine daily, Dr. Buyon reported, suggesting a protective effect.

Dr. Bevra Hahn, chief of rheumatology at UCLA David Geffen School of Medicine, Los Angeles, discussed her own approach to HCQ in the clinic. When faced with patients whose serology or symptoms are suggestive of lupus yet insufficient to fulfill criteria for a lupus diagnosis, Dr. Hahn said she initiates treatment with HCQ. "Can we prevent, delay, or make disease milder with [HCQ]? My answer to that is yes, and we do it a lot," Dr. Hahn said, citing a retrospective study that showed lupus onset to be delayed in people treated with HCQ (Lupus 2007;16:401-9).

Another recent case-control study (n = 481) bolstered the case for early use of HCQ. Investigators found that prompt use of HCQ after SLE diagnosis protected against cumulative damage after 3 years (J. Rheumatol. 2013 April 15 [doi:10.3899/jrheum.120572]).

Dr. Guillermo Ruiz-Irastorza of the University of the Basque Country, Barakaldo, Spain, gave an update at the congress on current approaches to antimalarials. "I am absolutely convinced that HCQ has a very wide range of good effects in lupus, and that the longer it is used, the better it works," he said in a later interview. "Our patients are now almost 100% on HCQ, and the outcome of most of them is amazing – obviously not only because of HCQ, but I am sure it plays a main role. We have seen very severe flares in patients stopping HCQ monotherapy. HCQ is also a crucial part of therapy in renal disease – along with lower prednisone doses, pulse methylprednisolone, and low-dose cyclophosphamide. That is our protocol, with excellent results."

A better understanding of the way HCQ works in lupus has only increased the perception of its clinical importance. In recent years, HCQ was found to have activity against antiphospholipid antibodies (Lupus 2010;19:460-9), which helps to explain its protective effect against pregnancy loss and thrombosis in SLE. More recently, HCQ has been found to antagonize toll-like receptors (TLR) 7 and 9, which are components of innate immunity erroneously activated in lupus. They are a target for new drug development in SLE (Curr. Allergy Asthma Rep. 2012;12:1-7).

Dr. David Pisetsky, professor of immunology at Duke University, Durham, N.C., discussed the implications of HCQ’s anti-TLR activity at the congress. "This relatively benign drug has powerful immunological effects, even though we don’t really think of it that way," he said. "When we’re talking about strategies to block TLR, we’ve already been probably doing it unbeknownst to us rather effectively."

Dr. Buyon, who was moderating Dr. Pisetsky’s talk, noted: "Maybe we’re really underselling ourselves [with HCQ]. Most of us confine ourselves to 6.5 mg/kg," she said, referring to the well-known risk of ocular toxicity and retinal changes associated with long-term HCQ treatment, requiring patients on HCQ to get eye exams yearly. Dr. Pisetsky agreed: "To me it would seem very worthwhile to push the dose to get more out of it."

Dr. Pisetsky and Dr. Buyon both expressed hope that manufacturers would seek to create an HCQ-like compound without the ocular risk, allowing the administration of higher doses with presumably more clinical effect. "But so far there’s been a very limited effort," Dr. Pisetsky said.

Another lupus researcher, rheumatologist and epidemiologist Dr. Sasha Bernatsky of McGill University, Montreal, expressed cautious optimism about some of the recent findings. Like Dr. Urowitz, Dr. Inanc, Dr. Buyon, Dr. Ruiz-Irastorz, and many other international scientists, Dr. Bernatsky is a member of the Systemic Lupus International Collaborating Clinics research group, which studies long-term outcomes in SLE.

"The exact possibilities, in terms of disease modification, remain a matter for further study," Dr. Bernatsky said in an interview, adding that while she strongly endorses HCQ for its many benefits, and recommends the drug in almost all SLE patients, she doesn’t fully understand the extremely strong effects that recent studies have suggested, related to nephritis, central nervous system manifestations, cancer, and overall survival.

Dr. Bernatsky struggles with the findings of a study that found HCQ associated with a 70% reduction in renal damage in lupus patients (Arthritis Rheum. 2009;61:830-9; Arthritis Rheum. 2009;61:1614-5). "I am amazed by that degree of disease-modifying effect in terms of active kidney disease, with [HCQ]," she said.

The recent finding of reduced seizures in lupus patients taking HCQ also surprised her. "A hazards ratio of 0.07 suggests that antimalarials reduce 93% of the risk of seizures, which is an incredibly large effect size."

One area of particular debate in HCQ and lupus concerns cancer risk. While Dr. Ruiz-Irastorza and his colleagues found a protective effect associated with HCQ in a cohort study of 235 patients (Ann. Rheum. Dis. 2007;66:815-7), "I did not believe the results at first," Dr. Ruiz-Irastorza said. "However, after discovering several papers showing biological plausibility for such an effect, I changed my mind. It seems to work by a number of different mechanisms, including inhibition of autophagy and sensitization of tumor cells to chemotherapy."

Dr. Bernatsky and SLICC investigators have studied malignancy risk and medication exposures in a large cohort (n = 16,409) of SLE patients (J. Autoimmun. 2013;42:130-5) without finding a protective effect associated with HCQ. "While I would not rule out some beneficial effects for cancer risk in the rheumatic diseases, I think the jury is still out," she said.

Nonetheless, Dr. Bernatsky said, "At our clinic, we keep most of our patients on antimalarials for years, and I hope it is similar in the United States and Europe. I’m happy for almost all SLE patients to be on HCQ because I think it’s a great drug."

None of the investigators mentioned have financial disclosures related to HCQ.

BUENOS AIRES – The antimalarial drug hydroxychloroquine is now standard first-line therapy in systemic lupus erythematosus, with most SLE patients taking it indefinitely alone or in addition to other medications.

It was not always this way. The past 15 years have seen what was long regarded as a mild drug, one commonly withdrawn after evidence of disease improvement, become more often compared to a miracle drug. Hydroxychloroquine (HCQ) is now considered indispensible in lupus, and is thought to confer a host of previously unrecognized benefits, with new ones being discovered every year.

Prospective and retrospective observational studies have found HCQ use associated with the prevention of lupus flares, less damage accrual, prolonged survival, less vascular damage, fewer thrombolic and cardiovascular events, better renal outcomes, and skin and joint improvement (J. Rheumatol. 2012;39:1769-71). One team of investigators has hypothesized that HCQ decreases cancer risk in people with lupus (Ann. Rheum. Dis. 2007;66:815-17). But other researchers have challenged some of these studies as potentially biased and not in keeping with observed clinical outcomes.

At the international congress on systemic lupus erythematosus, researchers discussed the latest findings related to HCQ in lupus, and shared thoughts on their implications for clinical practice.

Dr. Murray Urowitz, a senior scientist at the Toronto Western Research Institute, referred to results from a large multicenter cohort study (n = 1,631) that showed SLE patients taking antimalarial drugs in the absence of immunosuppressant medicines had significantly lower risk of seizures (Ann. Rheum. Dis. 2012;71:1502-9), possibly because HCQ is protective against flares, and seizures are thought to be caused by active neuropsychiatric lupus.

"We’ve heard this antimalarials story over and over again," Dr. Urowitz said, in commenting on the seizure findings. "Why aren’t all of our patients on antimalarials?"

HCQ use was seen as protective against cardiovascular disease (odds ratio 0.34, 95% confidence interval 0.16-0.71; P = .003) in a cohort of 306 SLE patients in Turkey, according to findings presented at the conference by Dr. Murat Inanc of Istanbul University (Lupus 2013;22[Suppl.]:O07).

In a separate presentation, Dr. Jill Buyon, director of the Lupus Center at New York University, reported encouraging preliminary data from a small, open-label study (n = 19) of HCQ in pregnant women with anti-SSA/Ro antibodies who previously had a child with cardiac manifestations of neonatal lupus, or cardiac-NL.

The major manifestation of cardiac-NL is heart block, an abnormality in which the heart beats too slowly. It is seen in about 2% of pregnancies in mothers with anti-SSA/Ro and anti-SSB/La serology, and the risk is 17.4% for those who have previously given birth to a child with cardiac-NL. Thus far, third degree heart block has been seen in only 1 of 17 pregnancies in women with a previous child with cardiac-NL taking 400 mg hydroxychloroquine daily, Dr. Buyon reported, suggesting a protective effect.

Dr. Bevra Hahn, chief of rheumatology at UCLA David Geffen School of Medicine, Los Angeles, discussed her own approach to HCQ in the clinic. When faced with patients whose serology or symptoms are suggestive of lupus yet insufficient to fulfill criteria for a lupus diagnosis, Dr. Hahn said she initiates treatment with HCQ. "Can we prevent, delay, or make disease milder with [HCQ]? My answer to that is yes, and we do it a lot," Dr. Hahn said, citing a retrospective study that showed lupus onset to be delayed in people treated with HCQ (Lupus 2007;16:401-9).

Another recent case-control study (n = 481) bolstered the case for early use of HCQ. Investigators found that prompt use of HCQ after SLE diagnosis protected against cumulative damage after 3 years (J. Rheumatol. 2013 April 15 [doi:10.3899/jrheum.120572]).

Dr. Guillermo Ruiz-Irastorza of the University of the Basque Country, Barakaldo, Spain, gave an update at the congress on current approaches to antimalarials. "I am absolutely convinced that HCQ has a very wide range of good effects in lupus, and that the longer it is used, the better it works," he said in a later interview. "Our patients are now almost 100% on HCQ, and the outcome of most of them is amazing – obviously not only because of HCQ, but I am sure it plays a main role. We have seen very severe flares in patients stopping HCQ monotherapy. HCQ is also a crucial part of therapy in renal disease – along with lower prednisone doses, pulse methylprednisolone, and low-dose cyclophosphamide. That is our protocol, with excellent results."

A better understanding of the way HCQ works in lupus has only increased the perception of its clinical importance. In recent years, HCQ was found to have activity against antiphospholipid antibodies (Lupus 2010;19:460-9), which helps to explain its protective effect against pregnancy loss and thrombosis in SLE. More recently, HCQ has been found to antagonize toll-like receptors (TLR) 7 and 9, which are components of innate immunity erroneously activated in lupus. They are a target for new drug development in SLE (Curr. Allergy Asthma Rep. 2012;12:1-7).

Dr. David Pisetsky, professor of immunology at Duke University, Durham, N.C., discussed the implications of HCQ’s anti-TLR activity at the congress. "This relatively benign drug has powerful immunological effects, even though we don’t really think of it that way," he said. "When we’re talking about strategies to block TLR, we’ve already been probably doing it unbeknownst to us rather effectively."

Dr. Buyon, who was moderating Dr. Pisetsky’s talk, noted: "Maybe we’re really underselling ourselves [with HCQ]. Most of us confine ourselves to 6.5 mg/kg," she said, referring to the well-known risk of ocular toxicity and retinal changes associated with long-term HCQ treatment, requiring patients on HCQ to get eye exams yearly. Dr. Pisetsky agreed: "To me it would seem very worthwhile to push the dose to get more out of it."

Dr. Pisetsky and Dr. Buyon both expressed hope that manufacturers would seek to create an HCQ-like compound without the ocular risk, allowing the administration of higher doses with presumably more clinical effect. "But so far there’s been a very limited effort," Dr. Pisetsky said.

Another lupus researcher, rheumatologist and epidemiologist Dr. Sasha Bernatsky of McGill University, Montreal, expressed cautious optimism about some of the recent findings. Like Dr. Urowitz, Dr. Inanc, Dr. Buyon, Dr. Ruiz-Irastorz, and many other international scientists, Dr. Bernatsky is a member of the Systemic Lupus International Collaborating Clinics research group, which studies long-term outcomes in SLE.

"The exact possibilities, in terms of disease modification, remain a matter for further study," Dr. Bernatsky said in an interview, adding that while she strongly endorses HCQ for its many benefits, and recommends the drug in almost all SLE patients, she doesn’t fully understand the extremely strong effects that recent studies have suggested, related to nephritis, central nervous system manifestations, cancer, and overall survival.

Dr. Bernatsky struggles with the findings of a study that found HCQ associated with a 70% reduction in renal damage in lupus patients (Arthritis Rheum. 2009;61:830-9; Arthritis Rheum. 2009;61:1614-5). "I am amazed by that degree of disease-modifying effect in terms of active kidney disease, with [HCQ]," she said.

The recent finding of reduced seizures in lupus patients taking HCQ also surprised her. "A hazards ratio of 0.07 suggests that antimalarials reduce 93% of the risk of seizures, which is an incredibly large effect size."

One area of particular debate in HCQ and lupus concerns cancer risk. While Dr. Ruiz-Irastorza and his colleagues found a protective effect associated with HCQ in a cohort study of 235 patients (Ann. Rheum. Dis. 2007;66:815-7), "I did not believe the results at first," Dr. Ruiz-Irastorza said. "However, after discovering several papers showing biological plausibility for such an effect, I changed my mind. It seems to work by a number of different mechanisms, including inhibition of autophagy and sensitization of tumor cells to chemotherapy."

Dr. Bernatsky and SLICC investigators have studied malignancy risk and medication exposures in a large cohort (n = 16,409) of SLE patients (J. Autoimmun. 2013;42:130-5) without finding a protective effect associated with HCQ. "While I would not rule out some beneficial effects for cancer risk in the rheumatic diseases, I think the jury is still out," she said.

Nonetheless, Dr. Bernatsky said, "At our clinic, we keep most of our patients on antimalarials for years, and I hope it is similar in the United States and Europe. I’m happy for almost all SLE patients to be on HCQ because I think it’s a great drug."

None of the investigators mentioned have financial disclosures related to HCQ.

BUENOS AIRES – Clinicians facing cases of severe refractory cutaneous lupus erythematosus – including in patients who smoke – have several treatment options, according to a prominent CLE researcher.

Dr. Victoria P. Werth, professor of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Affairs Medical Center, shared clinical strategies for treating CLE that is resistant to topical or intralesional treatments, and even systemic therapy with antimalarials.

"In terms of systemic therapy there are very few randomized placebo-controlled trials, and recommendations are based on expert opinion and retrospective case series. However, this is beginning to change," Dr. Werth said at an international congress on systemic lupus erythematosus. With the validated CLASI (CLE Disease Area and Severity Index) measure, which Dr. Werth and her colleagues introduced in 2005, "it’s been possible to prospectively follow patients who are being put on treatment."

Antimalarials are the established first-line systemic treatment for CLE, with studies showing hydroxychloroquine to be effective in 50%-70% of patients (Curr. Rheumatol. Rep. 2011;13: 300-7). "It’s worth it to give antimalarials to smokers," Dr. Werth said, citing findings from a prospective cohort study she coauthored (n = 218). She and her colleagues found that even though smoking was associated with more severe disease activity, current smokers requiring treatment with antimalarial agents alone actually improved more than nonsmokers treated with only these agents (Arch. Dermatol. 2012;148:317-21). When skin disease was refractory to antimalarials, the smokers responded less well than nonsmokers to additional therapies such as immunosuppressants.

Dr. Werth noted that patients who do not respond to hydroxychloroquine tend to be those with generalized discoid lupus. In her clinic, she said, patients are started with hydroxychloroquine at less than 6.5 mg/kg per day and given 6-8 weeks to respond. If they do not, quinacrine 100 mg/day is added. At another 6-8 weeks, if no improvement is seen, "stop the hydroxychloroquine and consider starting chloroquine at a dose of less than 3.5 mg/kg per day," Dr. Werth advised, noting that chloroquine has more eye toxicity than hydroxychloroquine.

Immunosuppressants are the usual next step after treatment failure with antimalarials; mycophenolate mofetil (MMF) has been shown in small, uncontrolled studies to be effective in CLE. Dr. Werth discussed a yet-unpublished open-label study (n = 13) that her group conducted in which azathioprine tended to be less effective than MMF in patients who had failed antimalarials.

Thalidomide is effective for refractory CLE, Dr. Werth noted, citing a Spanish study (n = 60) in which nearly all patients treated with 100 mg daily achieved a clinical response, as assessed by CLASI scores, with a complete response seen in 85% (Br. J. Dermatol. 2012;166:616-23).

"Many patients not responsive to antimalarials do respond to thalidomide, and sometimes a lower maintenance dose – as much as 25-50 mg/day or even once a week – can be helpful," she said. Patients, particularly those with discoid forms of CLE, can relapse when taken off thalidomide, but do respond when started again, she said, and kept on low-dose aspirin or hydroxychloroquine to prevent thrombotic events.

Thalidomide is used cautiously in CLE because of its serious adverse effect profile, which includes teratogenicity, amenorrhea, stroke, and peripheral neuropathy. And about 10% of patients, mostly smokers, prove refractory to immunosuppressives and/or thalidomide. For severely refractory patients, the thalidomide analog lenalidomide may have a role.

In Dr. Werth and her colleagues’ case series of lenalidomide in five severely refractory CLE patients, four improved, but one developed systemic lupus erythematosus, leading to speculation that the drug could activate T cells and trigger systemic disease (J. Am. Acad. Dermatol. 2012;66:571-82). In a Spanish open-label study evaluating 5-10 mg/day of lenalidomide in 15 patients, a complete response occurred in 12, and there were no reports of systemic lupus developing after a mean 15 months’ follow-up (Arthritis Res. Ther. 2012;14:R265). Dr. Werth called the lenalidomide findings "encouraging," but warned that the thalidomide derivatives "have complex mechanisms that need to be studied."

The biologic agents belimumab and rituximab offer other options for patients who fail thalidomide. Post-hoc analyses of randomized clinical trials of belimumab "showed that there seemed to be dose-dependent improvement in rash in patients relative to baseline – so there’s hope that further study will demonstrate that skin may benefit from treatment with belimumab," Dr. Werth said.

Rituximab also may be indicated for patients with bullous lupus that is unresponsive to treatment with dapsone or steroids. "It would make sense because this is clearly an autoantibody-driven process," Dr. Werth said. "There have been a number of reports of rituximab helping patients with refractory bullous lupus."

The CLASI copyright is owned by the University of Pennsylvania, Dr. Werth’s institution. Dr. Werth disclosed financial relationships with Pfizer, Novartis, Cephalon, Rigel, and Medimmune, and grant support from Celgene and Amgen.

BUENOS AIRES – Clinicians facing cases of severe refractory cutaneous lupus erythematosus – including in patients who smoke – have several treatment options, according to a prominent CLE researcher.

Dr. Victoria P. Werth, professor of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Affairs Medical Center, shared clinical strategies for treating CLE that is resistant to topical or intralesional treatments, and even systemic therapy with antimalarials.

"In terms of systemic therapy there are very few randomized placebo-controlled trials, and recommendations are based on expert opinion and retrospective case series. However, this is beginning to change," Dr. Werth said at an international congress on systemic lupus erythematosus. With the validated CLASI (CLE Disease Area and Severity Index) measure, which Dr. Werth and her colleagues introduced in 2005, "it’s been possible to prospectively follow patients who are being put on treatment."

Antimalarials are the established first-line systemic treatment for CLE, with studies showing hydroxychloroquine to be effective in 50%-70% of patients (Curr. Rheumatol. Rep. 2011;13: 300-7). "It’s worth it to give antimalarials to smokers," Dr. Werth said, citing findings from a prospective cohort study she coauthored (n = 218). She and her colleagues found that even though smoking was associated with more severe disease activity, current smokers requiring treatment with antimalarial agents alone actually improved more than nonsmokers treated with only these agents (Arch. Dermatol. 2012;148:317-21). When skin disease was refractory to antimalarials, the smokers responded less well than nonsmokers to additional therapies such as immunosuppressants.

Dr. Werth noted that patients who do not respond to hydroxychloroquine tend to be those with generalized discoid lupus. In her clinic, she said, patients are started with hydroxychloroquine at less than 6.5 mg/kg per day and given 6-8 weeks to respond. If they do not, quinacrine 100 mg/day is added. At another 6-8 weeks, if no improvement is seen, "stop the hydroxychloroquine and consider starting chloroquine at a dose of less than 3.5 mg/kg per day," Dr. Werth advised, noting that chloroquine has more eye toxicity than hydroxychloroquine.

Immunosuppressants are the usual next step after treatment failure with antimalarials; mycophenolate mofetil (MMF) has been shown in small, uncontrolled studies to be effective in CLE. Dr. Werth discussed a yet-unpublished open-label study (n = 13) that her group conducted in which azathioprine tended to be less effective than MMF in patients who had failed antimalarials.

Thalidomide is effective for refractory CLE, Dr. Werth noted, citing a Spanish study (n = 60) in which nearly all patients treated with 100 mg daily achieved a clinical response, as assessed by CLASI scores, with a complete response seen in 85% (Br. J. Dermatol. 2012;166:616-23).

"Many patients not responsive to antimalarials do respond to thalidomide, and sometimes a lower maintenance dose – as much as 25-50 mg/day or even once a week – can be helpful," she said. Patients, particularly those with discoid forms of CLE, can relapse when taken off thalidomide, but do respond when started again, she said, and kept on low-dose aspirin or hydroxychloroquine to prevent thrombotic events.

Thalidomide is used cautiously in CLE because of its serious adverse effect profile, which includes teratogenicity, amenorrhea, stroke, and peripheral neuropathy. And about 10% of patients, mostly smokers, prove refractory to immunosuppressives and/or thalidomide. For severely refractory patients, the thalidomide analog lenalidomide may have a role.

In Dr. Werth and her colleagues’ case series of lenalidomide in five severely refractory CLE patients, four improved, but one developed systemic lupus erythematosus, leading to speculation that the drug could activate T cells and trigger systemic disease (J. Am. Acad. Dermatol. 2012;66:571-82). In a Spanish open-label study evaluating 5-10 mg/day of lenalidomide in 15 patients, a complete response occurred in 12, and there were no reports of systemic lupus developing after a mean 15 months’ follow-up (Arthritis Res. Ther. 2012;14:R265). Dr. Werth called the lenalidomide findings "encouraging," but warned that the thalidomide derivatives "have complex mechanisms that need to be studied."

The biologic agents belimumab and rituximab offer other options for patients who fail thalidomide. Post-hoc analyses of randomized clinical trials of belimumab "showed that there seemed to be dose-dependent improvement in rash in patients relative to baseline – so there’s hope that further study will demonstrate that skin may benefit from treatment with belimumab," Dr. Werth said.

Rituximab also may be indicated for patients with bullous lupus that is unresponsive to treatment with dapsone or steroids. "It would make sense because this is clearly an autoantibody-driven process," Dr. Werth said. "There have been a number of reports of rituximab helping patients with refractory bullous lupus."

The CLASI copyright is owned by the University of Pennsylvania, Dr. Werth’s institution. Dr. Werth disclosed financial relationships with Pfizer, Novartis, Cephalon, Rigel, and Medimmune, and grant support from Celgene and Amgen.

BUENOS AIRES – Clinicians facing cases of severe refractory cutaneous lupus erythematosus – including in patients who smoke – have several treatment options, according to a prominent CLE researcher.

Dr. Victoria P. Werth, professor of dermatology at the Hospital of the University of Pennsylvania, Philadelphia, and chief of dermatology at the Philadelphia Veterans Affairs Medical Center, shared clinical strategies for treating CLE that is resistant to topical or intralesional treatments, and even systemic therapy with antimalarials.

"In terms of systemic therapy there are very few randomized placebo-controlled trials, and recommendations are based on expert opinion and retrospective case series. However, this is beginning to change," Dr. Werth said at an international congress on systemic lupus erythematosus. With the validated CLASI (CLE Disease Area and Severity Index) measure, which Dr. Werth and her colleagues introduced in 2005, "it’s been possible to prospectively follow patients who are being put on treatment."

Antimalarials are the established first-line systemic treatment for CLE, with studies showing hydroxychloroquine to be effective in 50%-70% of patients (Curr. Rheumatol. Rep. 2011;13: 300-7). "It’s worth it to give antimalarials to smokers," Dr. Werth said, citing findings from a prospective cohort study she coauthored (n = 218). She and her colleagues found that even though smoking was associated with more severe disease activity, current smokers requiring treatment with antimalarial agents alone actually improved more than nonsmokers treated with only these agents (Arch. Dermatol. 2012;148:317-21). When skin disease was refractory to antimalarials, the smokers responded less well than nonsmokers to additional therapies such as immunosuppressants.

Dr. Werth noted that patients who do not respond to hydroxychloroquine tend to be those with generalized discoid lupus. In her clinic, she said, patients are started with hydroxychloroquine at less than 6.5 mg/kg per day and given 6-8 weeks to respond. If they do not, quinacrine 100 mg/day is added. At another 6-8 weeks, if no improvement is seen, "stop the hydroxychloroquine and consider starting chloroquine at a dose of less than 3.5 mg/kg per day," Dr. Werth advised, noting that chloroquine has more eye toxicity than hydroxychloroquine.

Immunosuppressants are the usual next step after treatment failure with antimalarials; mycophenolate mofetil (MMF) has been shown in small, uncontrolled studies to be effective in CLE. Dr. Werth discussed a yet-unpublished open-label study (n = 13) that her group conducted in which azathioprine tended to be less effective than MMF in patients who had failed antimalarials.

Thalidomide is effective for refractory CLE, Dr. Werth noted, citing a Spanish study (n = 60) in which nearly all patients treated with 100 mg daily achieved a clinical response, as assessed by CLASI scores, with a complete response seen in 85% (Br. J. Dermatol. 2012;166:616-23).

"Many patients not responsive to antimalarials do respond to thalidomide, and sometimes a lower maintenance dose – as much as 25-50 mg/day or even once a week – can be helpful," she said. Patients, particularly those with discoid forms of CLE, can relapse when taken off thalidomide, but do respond when started again, she said, and kept on low-dose aspirin or hydroxychloroquine to prevent thrombotic events.

Thalidomide is used cautiously in CLE because of its serious adverse effect profile, which includes teratogenicity, amenorrhea, stroke, and peripheral neuropathy. And about 10% of patients, mostly smokers, prove refractory to immunosuppressives and/or thalidomide. For severely refractory patients, the thalidomide analog lenalidomide may have a role.

In Dr. Werth and her colleagues’ case series of lenalidomide in five severely refractory CLE patients, four improved, but one developed systemic lupus erythematosus, leading to speculation that the drug could activate T cells and trigger systemic disease (J. Am. Acad. Dermatol. 2012;66:571-82). In a Spanish open-label study evaluating 5-10 mg/day of lenalidomide in 15 patients, a complete response occurred in 12, and there were no reports of systemic lupus developing after a mean 15 months’ follow-up (Arthritis Res. Ther. 2012;14:R265). Dr. Werth called the lenalidomide findings "encouraging," but warned that the thalidomide derivatives "have complex mechanisms that need to be studied."

The biologic agents belimumab and rituximab offer other options for patients who fail thalidomide. Post-hoc analyses of randomized clinical trials of belimumab "showed that there seemed to be dose-dependent improvement in rash in patients relative to baseline – so there’s hope that further study will demonstrate that skin may benefit from treatment with belimumab," Dr. Werth said.

Rituximab also may be indicated for patients with bullous lupus that is unresponsive to treatment with dapsone or steroids. "It would make sense because this is clearly an autoantibody-driven process," Dr. Werth said. "There have been a number of reports of rituximab helping patients with refractory bullous lupus."

The CLASI copyright is owned by the University of Pennsylvania, Dr. Werth’s institution. Dr. Werth disclosed financial relationships with Pfizer, Novartis, Cephalon, Rigel, and Medimmune, and grant support from Celgene and Amgen.

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Women with systemic lupus erythematous can be advised that azathioprine does not appear to adversely affect their children in the long term if they become pregnant.

In a U.K. cross-sectional survey that included children who were 17 years or younger and born to mothers with systemic lupus erythematosus (SLE), a univariate analysis showed that exposure to azathioprine did not increase the risk of major infections (odds ratio, 1.6; 95% confidence interval 0.8-3.2; P = .15) or developmental problems (OR, 1.22; 95% CI 0.44-3.42; P = .702).

Only the age of the child at assessment was associated with an increased risk of developmental problems, which were defined as attention–deficit/hyperactivity disorder, developmental delay, special needs, or special-education needs (OR, 1.15; P = .003).

The study provides "reassuring data to counsel women who are planning pregnancy in the future," Dr. Mary Gayed said the annual meeting of the British Society for Rheumatology.

"We know, from previous research, that certain immunosuppressant agents are used in pregnancy for lupus to prevent flare and to ensure optimum outcome for mother and child," Dr. Gayed said, but there have been few studies looking at long-term outcomes.

Dr. Gayed, a rheumatologist at Sandwell and West Birmingham (England) Hospitals, noted that the few, small studies that have been conducted have suggested a link between azathioprine use and an increased risk of infection, the presence of anticardiolipin antibodies, and developmental delay in the child.

To investigate the long-term consequences of SLE drugs on children’s outcomes further, Dr. Gayed and her associates performed a retrospective study involving eight English centers. The study involved a total of 287 children aged 17 years or younger who were born to 200 women who, before giving birth, had satisfied four or more SLE criteria as defined by the American College of Rheumatology.

The women had a mean age of 32 years when they gave birth to their first child and had a median disease duration of 7.1 years. The majority (65%) of women were white, with 15% of mothers being Asian, 10% Afro-Caribbean, and the remainder of "other" or unspecified ethnicity.

Maternal antibodies were detected in the children, including anti-Ro with or without lupus anticoagulant in 38%, any antiphospholipid antibody in 43%, lupus anticoagulant specifically in 33%, and anticardiolipin (IgG or IgM) in 23%.

Dr. Gayed reported that aspirin was the most commonly used drug during pregnancy and that 202 children had been exposed to it during their mothers’ pregnancy, followed by prednisolone exposure in 169 children, hydroxychloroquine in 152, azathioprine in 88, and heparin in 70. Another three children were exposed to cyclosporine, and one to mycophenolate.

In terms of obstetric outcomes, only 10% of mothers had experienced preeclampsia, of which 6% of cases were severe enough to warrant induction. Intrauterine growth restriction occurred in 11% of pregnancies (not known in a further 6%), with only 7% of cases being severe enough for the mother to be induced.

The mean gestation period was 36.3 weeks and most children were born by vaginal delivery (49%), with 39% born by cesarean section, and 11% with the aid of forceps. The mean birth weight of neonates was 2.7 kg.

The children were assessed at a mean age of 4.6 years. Infection requiring hospital assessment occurred in 40 (14%) of the 287 children studied. The age at which infections occurred reflected the age at which children were assessed in the study, with around half of all infections seen occurring in children less than 5 years of age.

Around 40% of infections were chest-related, Dr. Gayed reported: 17% were caused by pneumonia, 12% bronchiolitis, 5% upper respiratory tract infection, and 7% tonsillitis.

The age of children at assessment, the duration of pregnancy, and birth weight were also not associated with infection risk.

Dr. Gayed had no conflicts of interest. One coauthor disclosed receiving consultancy fees and honoraria from Genentech and Roche and an educational grant from Aspreva/Vifor.

rhnews@frontlinemedcom.com

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BIRMINGHAM, ENGLAND – Lupus patients are most likely to have the metabolic syndrome early in the course of their disease if they have had the syndrome in the past, data from a large, prospective, observational study have shown.

The odds ratio (OR) for prior metabolic syndrome and having the syndrome in the first 2 years of follow-up was 4.83 in patients recently diagnosed with lupus (less than 15 months).

Hispanic ethnicity (OR, 3.47), elevated anti-dsDNA antibodies (OR, 1.86), age (OR, 1.03), and the use of a high peak prednisolone dose (40 mg) at enrollment (OR, 1.02) were also found to increase the risk for the metabolic syndrome early in the course of the disease.

Patients with systemic lupus erythematosus (SLE) are known to have an increased risk for the metabolic syndrome (Rheum. Dis. Clin. North Am. 2010;36:81-97), and this may contribute to increased cardiovascular risk and subsequent mortality, observed Dr. Ben Parker, a clinical research fellow at the Arthritis UK Epidemiology Unit, University of Manchester, England.

"It is fairly well established that SLE is an independent risk factor for cardiovascular disease," Dr. Parker said at the British Society for Rheumatology annual conference.

The mechanism of cardiovascular risk in SLE is not known, but it is likely to be "very complex and multifactorial," Dr. Parker added. "It is certainly related to ‘classic’ [cardiovascular] risk factors, systemic inflammation, some disease-specific risk factors, and the therapeutic exposures," he said.

Previously, Dr. Parker and his associates have shown that renal lupus, higher daily prednisolone doses, and being of Korean or Hispanic ethnicity are associated with the presence of the metabolic syndrome in SLE (Ann. Rheum. Dis. 2012 Sept. 3 [doi: 10.1136/annrheumdis-2012-202106]).

Their current investigation used data from the SLICC-RAS (Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis) study, a prospective, observational study initiated in 2000 that involves 30 centers in 11 countries in North America, Europe, and Asia. The aim was to identify factors that were associated with the metabolic syndrome during the first 2 years of follow-up.

A total of 1,494 of 1,686 patients with SLE who were diagnosed within the past 15 months in SLICC-RAS had sufficient data to determine their metabolic syndrome status and were included in the analysis. The mean age of patients at enrollment was 35.2 years, and the mean disease duration was 5.5 months.

The prevalence of the metabolic syndrome was 16% (n = 1,494) at enrollment, 12.6% (n = 1,065) at 1 year’s follow-up, and 13.6% (n = 895) at the 2-year follow-up assessment. Metabolic syndrome was defined according to International Diabetes Federation criteria, which require at least three of the following five factors to be present: obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and insulin resistance (Circulation 2009;120:1640-5).

There was fluctuation in metabolic status in the first 2 years of follow-up. Of 720 patients who had attended all three (enrollment, 1-year, and 2-year) assessments, 26.9% had the metabolic syndrome at any time during the first 2 years of follow-up, with 4.3% having the metabolic syndrome at all three assessments, 7.4% at two, and 15.3% at one.

"Around 73.1% of patients did not get the metabolic syndrome at all, and 14% developed it over the first 2 years," Dr. Parker reported. "Prevalent metabolic syndrome strongly predicts ongoing metabolic syndrome," he added.

A high corticosteroid dose at enrollment also increased the risk for the metabolic syndrome, Dr. Parker observed. The peak, daily dose of prednisolone used at enrollment was 40 mg, which decreased to 24.2 mg at the 1-year and 16.2 mg at the 2-year follow-up assessment. The respective average corticosteroid doses used were 20, 12.6, and 9.8 mg.

Dr. Parker concluded that the study data support a more personalized approach to managing patients with early, active SLE "in an attempt to rapidly and effectively control disease while trying to reduce corticosteroid doses," he said. The overall aim is to improve the cardiovascular risk profile for patients over time.

Arthritis Research UK funded the study. Dr. Parker had no conflicts of interest.

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.

BUENOS AIRES – A group of new studies on juvenile-onset systemic lupus erythematosus suggests that investigators are gaining a foothold on noninvasively monitoring renal disease, making more accurate diagnoses, and determining the prevalence of hippocampal atrophy in adolescents with the condition.

One of the three reports presented at the international congress on systemic lupus erythematosus (SLE) involved research from U.K. investigators on novel noninvasive biomarkers that can predict the course of renal disease in juvenile SLE, potentially allowing for earlier intervention, fewer kidney biopsies, and more accurate drug titration.

Researchers from Argentina revealed that new classification criteria for SLE, published in 2012, were more sensitive and specific in juvenile lupus patients than the widely used American College of Rheumatology criteria, which were last revised in 1997.

A third report from Brazil-based investigators found that atrophy of the hippocampus, the part of the brain associated with memory and learning, occurred in nearly two-thirds of a cohort of juvenile SLE patients.

Urine biomarkers for lupus nephritis

Dr. Louise Watson of Alder Hey Children’s NHS Hospital, Liverpool, England, presented findings on novel urine biomarkers from a multicenter, prospective cohort study of 64 SLE patients aged 16 years and younger. "We were keen to look for better ways to monitor the disease through biomarkers, and to move from a more reactive to a more proactive approach," Dr. Watson said at the meeting.

Rather than wait until the onset of proteinuria to start treatment, reliable noninvasive biomarkers "could allow disease to be detected at a much earlier time point, and hopefully help us try and prevent some of the irreversible kidney damage that we might see" associated with juvenile-onset SLE.

Dr. Watson and her colleagues looked at both standard and novel biomarkers in the cohort, and found that two novel ones – monocyte chemoattractant protein 1 (MCP1) and neutrophil gelatinase associated lipocalin (NGAL) – predicted changes in the course of renal disease over a 2-year period. MCP1 was highly predictive of disease improvement, and NGAL of disease progression.

MCP1 at a concentration of 343 pg/mL was a significant predictor of improvement in renal disease (P = .013; specificity 71%, sensitivity 70%), the researchers found. Meanwhile, NGAL at 30 ng/mL predicted worsening renal disease (P = .04; specificity 60%, sensitivity 61%).

Urine MCP1 and NGAL changed as subsequent renal disease changed (MCP1, P = .015; NGAL, P = .038), while standard biomarkers (erythrocyte sedimentation rate, anti-double stranded DNA, urine albumin to creatinine ratio, creatinine, complement 3, complement 4, and lymphocytes) did not predict disease activity changes. MCP1 and C3 were seen in a multivariate analysis as independent variables (P less than .001) for active renal disease (Lupus 2013;22 [Suppl.]:O13).

The fact that MCP1 and NGAL are so specific, Dr. Watson said, "may be because they’re expressed directly from the kidney cells. Perhaps we need to begin to validate some of these and move them towards commercialization so we can look towards earlier intervention and monitoring to try and improve the outcome in our patients."

New disease criteria perform better than old

In a separate talk at the congress (Lupus 2013;22[Suppl.]:O12), Dr. Marìa M. Katsicas of the Hospital de Pediatría Prof. Dr. Juan P. Garrahan, in Buenos Aires, presented results from a study comparing the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, published last year (Arthritis Rheum. 2012;64:2677-86), with the revised American College of Rheumatology criteria for SLE (Arthritis Rheum. 1997;40:1725) in a cohort of juvenile patients.

"The ACR criteria have not been completely evaluated in pediatric patients," Dr. Katsicas explained. "Only one publication describes sensitivity and specificity in Brazilian children" (Clin. Exp. Rheumatol. 1994;12:83-7).

For Dr. Katsicas and her colleagues’ study, experienced pediatric rheumatologists reviewed medical records and prospective data for 107 patients with juvenile-onset SLE, and 124 controls with juvenile idiopathic arthritis, juvenile dermatomyositis, autoimmune hepatitis, juvenile systemic sclerosis, ANCA-associated vasculitis, or Henoch-Schönlein purpura.

Using the SLICC SLE criteria, all of the SLE cases were correctly identified, while under the ACR 1997 criteria, six cases were missed. Sensitivity for the new criteria was 100%, compared with 86% for the ACR criteria, while specificity was 98% and 96% respectively. "It is very important to note that six patients were correctly identified by SLICC and not ACR," Dr. Katsicas said.

Many patients develop hippocampal atrophy

Dr. Simone Appenzeller of the State University of Campinas, São Paulo, Brazil, and her colleagues reported finding MRI evidence of hippocampal atrophy (in one or both lobes) in 24 of 40 juvenile SLE patients, compared with only 1 of 40 controls.

"Studies have suggested that in the hippocampus, which is the brain area important to memory and learning, [there] may be a specific target for some autoantibodies in neuropsychiatric SLE," Dr. Appenzeller told the congress.

"We have previously shown in adults that there is hippocampal atrophy associated with the total dose of corticosteroids," Dr. Appenzeller said (Ann. Rheum. Dis. 2006;65:1585-9), noting that the association was found once again in the current study (P = .019). Atrophy was also associated with anticardiolipin antibodies (P = .009), vasculitis (P = .042), disease duration (P = .001), cognitive impairment (P = .005), age of disease onset (P = .008) and current age (P = .013). However, disease activity and damage scores were not associated with hippocampal atrophy.

Patients that may have hippocampal atrophy should be followed more closely with MRI and cognitive evaluation, Dr. Appenzeller advised, adding that the findings "could allow us to develop strategies to prevent its occurrence" (Lupus 2013;22[Suppl.]:O15)

Neither Dr. Katsicas nor Dr. Appenzeller reported conflicts of interest. Dr. Watson disclosed that Abbott Laboratories provided the NGAL assay for her group’s study at no cost.

BIRMINGHAM, ENGLAND – Patients with Sjögren’s syndrome had a diverse and high rate of long-term complications over the course of a 25-year review of cases seen at a single center.

Between 1986 and 2011, 152 patients with primary Sjögren’s syndrome were treated at University College London (UCL), England. More than half of the patients developed serological abnormalities (51.3%), followed by additional autoimmune diseases in 49.3% and systemic malignancy in 28.3%.

“We found that the main complications were extraglandular,” Ms. Esha Abrol, a fifth-year medical student at UCL, reported at the British Society for Rheumatology annual conference. Extraglandular manifestations occurred in 71% of patients, and 20% of patients experiencing local or glandular complications, such as parotid swelling.

These data highlight that primary Sjögren’s syndrome is perhaps not as benign as people might think, Ms. Abrol suggested, and that an increase in the risk of non-Hodgkin’s lymphoma (NHL) is not the only problem to watch out for.

The majority of the study population was female (91.4%) and white (86.8%); three-quarters (75.7%) had antinuclear antibodies, 55.9% had anti-Ro/SS-A antibodies, 35.5% anti-La/SS-B antibodies, 54.6% were rheumatoid factor positive, and 36.8% had hypergammaglobulinemia. The mean age at diagnosis was 54.4 years.

At the time of the case review, at a mean of 12.4 years’ follow-up, 55.9% of patients were still alive; 26.6% had been lost to follow-up, which was mainly from old age, and 18.5% had died. The mean age at death was 72 years.

“One of the most common extraglandular manifestations was additional autoimmune diseases,” Ms. Abrol reported. These included autoimmune thyroid disease (for example, Hashimoto’s thyroiditis and Graves’ disease) in 15.8% of patients. Other autoimmune diseases included those affecting the blood vessels (vasculitis occurred in 10.5% of patients), skin (10.5%), gastrointestinal system (10.5%), lungs (7.2%), and kidneys (6.5%).

Ms. Abrol observed that patients who developed autoimmune diseases were more likely to be female than male, have anti-Ro/SS-A or Anti-La/SS-B antibodies, and hypergammaglobulinemia. Nineteen percent of patients had more than one autoimmune disease in addition to Sjögren’s, with one patient having four additional autoimmune diseases.

As expected, the most common type of malignancy seen was NHL, which occurred in approximately one in ten patients (10.5%). A range of other malignancies was seen, including ovarian and cervical (3.3%), bladder (2.6%), skin (2.6%), lung (2.0%), and oropharyngeal (2.0%) cancers, to name a few.

The risk for malignancy was higher in patients older than 50 years, with an odds ratio (OR) of 9.6 (P = .03). Patients who developed cancer were also more likely to be negative for Anti-RNP antibodies (OR, 4.9; P = .06).

The risk for NHL was increased in patients who had vasculitis (OR, 10.5; P less than .001) and in those with glandular manifestations (OR, 3.4; P = .041).

There were other numerous complications, including serologic alterations (51.3%), principally hypergammaglobulinemia, Raynaud’s syndrome (30.9%), and arthritis (19.7%). Peripheral and central nervous system complications were also seen in 15.8% and 9.2% of patients.

These data highlight that primary Sjögren’s syndrome carries a higher disease burden than previously suggested, Ms. Abrol concluded, noting that they can be used to inform patients on what may happen to them long-term.

Ms. Abrol had no conflicts of interest.

BIRMINGHAM, ENGLAND – Patients with Sjögren’s syndrome had a diverse and high rate of long-term complications over the course of a 25-year review of cases seen at a single center.

Between 1986 and 2011, 152 patients with primary Sjögren’s syndrome were treated at University College London (UCL), England. More than half of the patients developed serological abnormalities (51.3%), followed by additional autoimmune diseases in 49.3% and systemic malignancy in 28.3%.

“We found that the main complications were extraglandular,” Ms. Esha Abrol, a fifth-year medical student at UCL, reported at the British Society for Rheumatology annual conference. Extraglandular manifestations occurred in 71% of patients, and 20% of patients experiencing local or glandular complications, such as parotid swelling.

These data highlight that primary Sjögren’s syndrome is perhaps not as benign as people might think, Ms. Abrol suggested, and that an increase in the risk of non-Hodgkin’s lymphoma (NHL) is not the only problem to watch out for.

The majority of the study population was female (91.4%) and white (86.8%); three-quarters (75.7%) had antinuclear antibodies, 55.9% had anti-Ro/SS-A antibodies, 35.5% anti-La/SS-B antibodies, 54.6% were rheumatoid factor positive, and 36.8% had hypergammaglobulinemia. The mean age at diagnosis was 54.4 years.

At the time of the case review, at a mean of 12.4 years’ follow-up, 55.9% of patients were still alive; 26.6% had been lost to follow-up, which was mainly from old age, and 18.5% had died. The mean age at death was 72 years.

“One of the most common extraglandular manifestations was additional autoimmune diseases,” Ms. Abrol reported. These included autoimmune thyroid disease (for example, Hashimoto’s thyroiditis and Graves’ disease) in 15.8% of patients. Other autoimmune diseases included those affecting the blood vessels (vasculitis occurred in 10.5% of patients), skin (10.5%), gastrointestinal system (10.5%), lungs (7.2%), and kidneys (6.5%).

Ms. Abrol observed that patients who developed autoimmune diseases were more likely to be female than male, have anti-Ro/SS-A or Anti-La/SS-B antibodies, and hypergammaglobulinemia. Nineteen percent of patients had more than one autoimmune disease in addition to Sjögren’s, with one patient having four additional autoimmune diseases.

As expected, the most common type of malignancy seen was NHL, which occurred in approximately one in ten patients (10.5%). A range of other malignancies was seen, including ovarian and cervical (3.3%), bladder (2.6%), skin (2.6%), lung (2.0%), and oropharyngeal (2.0%) cancers, to name a few.

The risk for malignancy was higher in patients older than 50 years, with an odds ratio (OR) of 9.6 (P = .03). Patients who developed cancer were also more likely to be negative for Anti-RNP antibodies (OR, 4.9; P = .06).

The risk for NHL was increased in patients who had vasculitis (OR, 10.5; P less than .001) and in those with glandular manifestations (OR, 3.4; P = .041).

There were other numerous complications, including serologic alterations (51.3%), principally hypergammaglobulinemia, Raynaud’s syndrome (30.9%), and arthritis (19.7%). Peripheral and central nervous system complications were also seen in 15.8% and 9.2% of patients.

These data highlight that primary Sjögren’s syndrome carries a higher disease burden than previously suggested, Ms. Abrol concluded, noting that they can be used to inform patients on what may happen to them long-term.

Ms. Abrol had no conflicts of interest.

BIRMINGHAM, ENGLAND – Patients with Sjögren’s syndrome had a diverse and high rate of long-term complications over the course of a 25-year review of cases seen at a single center.

Between 1986 and 2011, 152 patients with primary Sjögren’s syndrome were treated at University College London (UCL), England. More than half of the patients developed serological abnormalities (51.3%), followed by additional autoimmune diseases in 49.3% and systemic malignancy in 28.3%.

“We found that the main complications were extraglandular,” Ms. Esha Abrol, a fifth-year medical student at UCL, reported at the British Society for Rheumatology annual conference. Extraglandular manifestations occurred in 71% of patients, and 20% of patients experiencing local or glandular complications, such as parotid swelling.

These data highlight that primary Sjögren’s syndrome is perhaps not as benign as people might think, Ms. Abrol suggested, and that an increase in the risk of non-Hodgkin’s lymphoma (NHL) is not the only problem to watch out for.

The majority of the study population was female (91.4%) and white (86.8%); three-quarters (75.7%) had antinuclear antibodies, 55.9% had anti-Ro/SS-A antibodies, 35.5% anti-La/SS-B antibodies, 54.6% were rheumatoid factor positive, and 36.8% had hypergammaglobulinemia. The mean age at diagnosis was 54.4 years.

At the time of the case review, at a mean of 12.4 years’ follow-up, 55.9% of patients were still alive; 26.6% had been lost to follow-up, which was mainly from old age, and 18.5% had died. The mean age at death was 72 years.

“One of the most common extraglandular manifestations was additional autoimmune diseases,” Ms. Abrol reported. These included autoimmune thyroid disease (for example, Hashimoto’s thyroiditis and Graves’ disease) in 15.8% of patients. Other autoimmune diseases included those affecting the blood vessels (vasculitis occurred in 10.5% of patients), skin (10.5%), gastrointestinal system (10.5%), lungs (7.2%), and kidneys (6.5%).

Ms. Abrol observed that patients who developed autoimmune diseases were more likely to be female than male, have anti-Ro/SS-A or Anti-La/SS-B antibodies, and hypergammaglobulinemia. Nineteen percent of patients had more than one autoimmune disease in addition to Sjögren’s, with one patient having four additional autoimmune diseases.

As expected, the most common type of malignancy seen was NHL, which occurred in approximately one in ten patients (10.5%). A range of other malignancies was seen, including ovarian and cervical (3.3%), bladder (2.6%), skin (2.6%), lung (2.0%), and oropharyngeal (2.0%) cancers, to name a few.

The risk for malignancy was higher in patients older than 50 years, with an odds ratio (OR) of 9.6 (P = .03). Patients who developed cancer were also more likely to be negative for Anti-RNP antibodies (OR, 4.9; P = .06).

The risk for NHL was increased in patients who had vasculitis (OR, 10.5; P less than .001) and in those with glandular manifestations (OR, 3.4; P = .041).

There were other numerous complications, including serologic alterations (51.3%), principally hypergammaglobulinemia, Raynaud’s syndrome (30.9%), and arthritis (19.7%). Peripheral and central nervous system complications were also seen in 15.8% and 9.2% of patients.

These data highlight that primary Sjögren’s syndrome carries a higher disease burden than previously suggested, Ms. Abrol concluded, noting that they can be used to inform patients on what may happen to them long-term.

Ms. Abrol had no conflicts of interest.

BUENOS AIRES – Traditional tools such as the Framingham risk score have long been known to underestimate cardiovascular risk in people with systemic lupus erythematosus.

At the international congress on systemic lupus erythematosus, Dr. Michelle Petri of Johns Hopkins University, Baltimore, presented data in support of a novel risk-assessment formula to calculate the 10-year risk of a cardiovascular event (CVE). The tool combines the traditional cardiovascular disease risk factors of age, sex, high blood pressure, high cholesterol, smoking, diabetes, and body mass index (BMI), with three lupus-specific factors: a SLEDAI (SLE Disease Activity Index) score of 2 or higher, lupus anticoagulant, and a low mean complement 3 (C3) level.

Under both this and the Framingham algorithms, a 50-year old woman with SLE with a BMI of 23 kg/m², systolic blood pressure of 150 mm Hg, and high cholesterol has about an 8% 10-year risk of a CVE. However, if she also has lupus anticoagulant, high disease activity, or a low C3 level, her risk rises to 15%-18% under the SLE-specific system, whereas her Framingham score, which does not measure these, would remain at 8%.

Courtesy of Keith Weller/Johns Hopkins Medicine

Dr. Petri told the conference that with rheumatoid arthritis, the advice has been to multiply an existing risk score by 1.5 when the patient has certain evidence of disease. "I thought we could do better than that in lupus, because we could derive a formula using actual data," she said.

"We know that traditional CV risk factors do predict actual events and also predict the progression of subclinical atherosclerosis. Even after we adjust, though, for every traditional cardiovascular risk factor, lupus patients still have a twofold increase in coronary calcium over controls – so obviously lupus-specific factors must be in the formula as well."

The data used to derive the new scoring system came from a cohort of 1,342 lupus patients (93% female) treated at the Johns Hopkins Lupus Center. None had a history of CVEs during the first 2 years of follow-up. Over the study period, 109 incident CVEs occurred in the cohort, including 52 strokes and 26 myocardial infarctions.

Dr. Petri and her colleagues used Cox proportional hazards models to determine the baseline variables affecting the risk of a subsequent CVE. Using the results, they derived a formula to calculate the 10-year risk of a CVE. For each of the risk factors, they investigators converted the hazard ratio into a simple integer score to simplify calculation in clinical practice. By adding up the integers and using a slide rule that stands in for the exponential equation, clinicians can translate the integer score into a risk percentage.

Dr. Petri acknowledged as limitations of the study its single-site design; the fact that the Johns Hopkins Lupus Center does not routinely perform cholesterol screening; and that the study reflects care from 1988 onward, where more recent data could reflect a better standard of care. "This needs to be independently validated," she said.

In another multivariate analysis of cardiovascular disease (CVD) risk factors in lupus, a cohort of 306 consecutive SLE patients at a clinic in Istanbul, Turkey, revealed pericarditis, lymphopenia, thrombocytopenia, and psychosis to be significantly associated with nonfatal CVD.

Dr. Murat Inanc of Istanbul University, the lead author of the study, said that 15.2% of the cohort (mean age, 40.2 years; 89% female) had clinical evidence of CVD. Many of them also had traditional risk factors. "The usual suspects are there – hypertension, high cholesterol, metabolic syndrome – but we also found disease-specific features more present in patients with CV involvement," Dr. Inanc said.

Patients with evidence of CVD were older and had longer disease duration, significantly more organ damage, and a higher number of American College of Rheumatology criteria for SLE. "We think disease severity takes almost equal importance with traditional risk factors in this population," he said. Treatment with cyclophosphamide was also seen as a risk factor, although it is likely related to disease severity, he told the congress.

Dr. Inanc noted that the conclusions that can be drawn from the study are limited by its single-site design and lack of data on subclinical CVD. Cumulative corticosteroid use was not investigated, and investigators did not have information on immunosuppressive use in the cohort.

Dr. Murray Urowitz, of the Toronto Western Research Institute, presented findings from an international, multicenter inception cohort of 1,401 SLE patients. The goal of the study was to determine factors at diagnosis that are predictive of the development of premature atherosclerosis. Dr. Urowitz and his colleagues looked at age, sex, diabetes, smoking, obesity, low-density lipoprotein cholesterol, and creatinine. A multivariate analysis showed that only age and male sex were significant risk factors for atherosclerotic vascular events after a mean 5 years’ follow-up. "The implication here is these risk factors take more time to have their maximum effect, and in the first decade it’s hard to have more than age and sex," Dr. Urowitz told the congress.

Also at the congress, Dr. Maureen McMahon of the University of California, Los Angeles, gave a presentation on a panel of biomarkers found to be predictive of current, progressive, or acquired carotid plaque in a cohort of SLE patients.

For their research, Dr. McMahon and her colleagues looked at 210 female SLE patients and 100 age-matched controls who underwent ultrasound imaging of their carotid arteries at baseline and after a mean 29 months of follow-up. Nearly a third of SLE patients had evidence of plaque on follow-up.

The researchers found that three or more of the following factors at baseline were 94% predictive of plaque: age 48 or older, evidence of proinflammatory high-density lipoprotein cholesterol, plasma leptin of 34 ng/dL or greater, homocysteine of 12 mmol/L or greater, and plasma levels of sTWEAK (soluble tumor necrosis factor–like weak inducer of apoptosis) of 373 pg/mL or greater. Any one of these factors plus diabetes was also predictive. Patients with at least three indicators (or one plus diabetes) saw a 28-fold increased odds for the longitudinal presence of carotid plaque (95% confidence interval, 10.6-72.7; P less than .001) and a significantly increased rate of progression of both plaque and intima-media thickness.

None of the investigators disclosed financial relationships related to these studies.

BUENOS AIRES – Traditional tools such as the Framingham risk score have long been known to underestimate cardiovascular risk in people with systemic lupus erythematosus.

At the international congress on systemic lupus erythematosus, Dr. Michelle Petri of Johns Hopkins University, Baltimore, presented data in support of a novel risk-assessment formula to calculate the 10-year risk of a cardiovascular event (CVE). The tool combines the traditional cardiovascular disease risk factors of age, sex, high blood pressure, high cholesterol, smoking, diabetes, and body mass index (BMI), with three lupus-specific factors: a SLEDAI (SLE Disease Activity Index) score of 2 or higher, lupus anticoagulant, and a low mean complement 3 (C3) level.

Under both this and the Framingham algorithms, a 50-year old woman with SLE with a BMI of 23 kg/m², systolic blood pressure of 150 mm Hg, and high cholesterol has about an 8% 10-year risk of a CVE. However, if she also has lupus anticoagulant, high disease activity, or a low C3 level, her risk rises to 15%-18% under the SLE-specific system, whereas her Framingham score, which does not measure these, would remain at 8%.

Courtesy of Keith Weller/Johns Hopkins Medicine

Dr. Petri told the conference that with rheumatoid arthritis, the advice has been to multiply an existing risk score by 1.5 when the patient has certain evidence of disease. "I thought we could do better than that in lupus, because we could derive a formula using actual data," she said.

"We know that traditional CV risk factors do predict actual events and also predict the progression of subclinical atherosclerosis. Even after we adjust, though, for every traditional cardiovascular risk factor, lupus patients still have a twofold increase in coronary calcium over controls – so obviously lupus-specific factors must be in the formula as well."

The data used to derive the new scoring system came from a cohort of 1,342 lupus patients (93% female) treated at the Johns Hopkins Lupus Center. None had a history of CVEs during the first 2 years of follow-up. Over the study period, 109 incident CVEs occurred in the cohort, including 52 strokes and 26 myocardial infarctions.

Dr. Petri and her colleagues used Cox proportional hazards models to determine the baseline variables affecting the risk of a subsequent CVE. Using the results, they derived a formula to calculate the 10-year risk of a CVE. For each of the risk factors, they investigators converted the hazard ratio into a simple integer score to simplify calculation in clinical practice. By adding up the integers and using a slide rule that stands in for the exponential equation, clinicians can translate the integer score into a risk percentage.

Dr. Petri acknowledged as limitations of the study its single-site design; the fact that the Johns Hopkins Lupus Center does not routinely perform cholesterol screening; and that the study reflects care from 1988 onward, where more recent data could reflect a better standard of care. "This needs to be independently validated," she said.

In another multivariate analysis of cardiovascular disease (CVD) risk factors in lupus, a cohort of 306 consecutive SLE patients at a clinic in Istanbul, Turkey, revealed pericarditis, lymphopenia, thrombocytopenia, and psychosis to be significantly associated with nonfatal CVD.

Dr. Murat Inanc of Istanbul University, the lead author of the study, said that 15.2% of the cohort (mean age, 40.2 years; 89% female) had clinical evidence of CVD. Many of them also had traditional risk factors. "The usual suspects are there – hypertension, high cholesterol, metabolic syndrome – but we also found disease-specific features more present in patients with CV involvement," Dr. Inanc said.

Patients with evidence of CVD were older and had longer disease duration, significantly more organ damage, and a higher number of American College of Rheumatology criteria for SLE. "We think disease severity takes almost equal importance with traditional risk factors in this population," he said. Treatment with cyclophosphamide was also seen as a risk factor, although it is likely related to disease severity, he told the congress.

Dr. Inanc noted that the conclusions that can be drawn from the study are limited by its single-site design and lack of data on subclinical CVD. Cumulative corticosteroid use was not investigated, and investigators did not have information on immunosuppressive use in the cohort.

Dr. Murray Urowitz, of the Toronto Western Research Institute, presented findings from an international, multicenter inception cohort of 1,401 SLE patients. The goal of the study was to determine factors at diagnosis that are predictive of the development of premature atherosclerosis. Dr. Urowitz and his colleagues looked at age, sex, diabetes, smoking, obesity, low-density lipoprotein cholesterol, and creatinine. A multivariate analysis showed that only age and male sex were significant risk factors for atherosclerotic vascular events after a mean 5 years’ follow-up. "The implication here is these risk factors take more time to have their maximum effect, and in the first decade it’s hard to have more than age and sex," Dr. Urowitz told the congress.

Also at the congress, Dr. Maureen McMahon of the University of California, Los Angeles, gave a presentation on a panel of biomarkers found to be predictive of current, progressive, or acquired carotid plaque in a cohort of SLE patients.

For their research, Dr. McMahon and her colleagues looked at 210 female SLE patients and 100 age-matched controls who underwent ultrasound imaging of their carotid arteries at baseline and after a mean 29 months of follow-up. Nearly a third of SLE patients had evidence of plaque on follow-up.

The researchers found that three or more of the following factors at baseline were 94% predictive of plaque: age 48 or older, evidence of proinflammatory high-density lipoprotein cholesterol, plasma leptin of 34 ng/dL or greater, homocysteine of 12 mmol/L or greater, and plasma levels of sTWEAK (soluble tumor necrosis factor–like weak inducer of apoptosis) of 373 pg/mL or greater. Any one of these factors plus diabetes was also predictive. Patients with at least three indicators (or one plus diabetes) saw a 28-fold increased odds for the longitudinal presence of carotid plaque (95% confidence interval, 10.6-72.7; P less than .001) and a significantly increased rate of progression of both plaque and intima-media thickness.

None of the investigators disclosed financial relationships related to these studies.

BUENOS AIRES – Traditional tools such as the Framingham risk score have long been known to underestimate cardiovascular risk in people with systemic lupus erythematosus.

At the international congress on systemic lupus erythematosus, Dr. Michelle Petri of Johns Hopkins University, Baltimore, presented data in support of a novel risk-assessment formula to calculate the 10-year risk of a cardiovascular event (CVE). The tool combines the traditional cardiovascular disease risk factors of age, sex, high blood pressure, high cholesterol, smoking, diabetes, and body mass index (BMI), with three lupus-specific factors: a SLEDAI (SLE Disease Activity Index) score of 2 or higher, lupus anticoagulant, and a low mean complement 3 (C3) level.

Under both this and the Framingham algorithms, a 50-year old woman with SLE with a BMI of 23 kg/m², systolic blood pressure of 150 mm Hg, and high cholesterol has about an 8% 10-year risk of a CVE. However, if she also has lupus anticoagulant, high disease activity, or a low C3 level, her risk rises to 15%-18% under the SLE-specific system, whereas her Framingham score, which does not measure these, would remain at 8%.

Courtesy of Keith Weller/Johns Hopkins Medicine

Dr. Petri told the conference that with rheumatoid arthritis, the advice has been to multiply an existing risk score by 1.5 when the patient has certain evidence of disease. "I thought we could do better than that in lupus, because we could derive a formula using actual data," she said.

"We know that traditional CV risk factors do predict actual events and also predict the progression of subclinical atherosclerosis. Even after we adjust, though, for every traditional cardiovascular risk factor, lupus patients still have a twofold increase in coronary calcium over controls – so obviously lupus-specific factors must be in the formula as well."

The data used to derive the new scoring system came from a cohort of 1,342 lupus patients (93% female) treated at the Johns Hopkins Lupus Center. None had a history of CVEs during the first 2 years of follow-up. Over the study period, 109 incident CVEs occurred in the cohort, including 52 strokes and 26 myocardial infarctions.

Dr. Petri and her colleagues used Cox proportional hazards models to determine the baseline variables affecting the risk of a subsequent CVE. Using the results, they derived a formula to calculate the 10-year risk of a CVE. For each of the risk factors, they investigators converted the hazard ratio into a simple integer score to simplify calculation in clinical practice. By adding up the integers and using a slide rule that stands in for the exponential equation, clinicians can translate the integer score into a risk percentage.

Dr. Petri acknowledged as limitations of the study its single-site design; the fact that the Johns Hopkins Lupus Center does not routinely perform cholesterol screening; and that the study reflects care from 1988 onward, where more recent data could reflect a better standard of care. "This needs to be independently validated," she said.

In another multivariate analysis of cardiovascular disease (CVD) risk factors in lupus, a cohort of 306 consecutive SLE patients at a clinic in Istanbul, Turkey, revealed pericarditis, lymphopenia, thrombocytopenia, and psychosis to be significantly associated with nonfatal CVD.

Dr. Murat Inanc of Istanbul University, the lead author of the study, said that 15.2% of the cohort (mean age, 40.2 years; 89% female) had clinical evidence of CVD. Many of them also had traditional risk factors. "The usual suspects are there – hypertension, high cholesterol, metabolic syndrome – but we also found disease-specific features more present in patients with CV involvement," Dr. Inanc said.

Patients with evidence of CVD were older and had longer disease duration, significantly more organ damage, and a higher number of American College of Rheumatology criteria for SLE. "We think disease severity takes almost equal importance with traditional risk factors in this population," he said. Treatment with cyclophosphamide was also seen as a risk factor, although it is likely related to disease severity, he told the congress.

Dr. Inanc noted that the conclusions that can be drawn from the study are limited by its single-site design and lack of data on subclinical CVD. Cumulative corticosteroid use was not investigated, and investigators did not have information on immunosuppressive use in the cohort.

Dr. Murray Urowitz, of the Toronto Western Research Institute, presented findings from an international, multicenter inception cohort of 1,401 SLE patients. The goal of the study was to determine factors at diagnosis that are predictive of the development of premature atherosclerosis. Dr. Urowitz and his colleagues looked at age, sex, diabetes, smoking, obesity, low-density lipoprotein cholesterol, and creatinine. A multivariate analysis showed that only age and male sex were significant risk factors for atherosclerotic vascular events after a mean 5 years’ follow-up. "The implication here is these risk factors take more time to have their maximum effect, and in the first decade it’s hard to have more than age and sex," Dr. Urowitz told the congress.

Also at the congress, Dr. Maureen McMahon of the University of California, Los Angeles, gave a presentation on a panel of biomarkers found to be predictive of current, progressive, or acquired carotid plaque in a cohort of SLE patients.

For their research, Dr. McMahon and her colleagues looked at 210 female SLE patients and 100 age-matched controls who underwent ultrasound imaging of their carotid arteries at baseline and after a mean 29 months of follow-up. Nearly a third of SLE patients had evidence of plaque on follow-up.

The researchers found that three or more of the following factors at baseline were 94% predictive of plaque: age 48 or older, evidence of proinflammatory high-density lipoprotein cholesterol, plasma leptin of 34 ng/dL or greater, homocysteine of 12 mmol/L or greater, and plasma levels of sTWEAK (soluble tumor necrosis factor–like weak inducer of apoptosis) of 373 pg/mL or greater. Any one of these factors plus diabetes was also predictive. Patients with at least three indicators (or one plus diabetes) saw a 28-fold increased odds for the longitudinal presence of carotid plaque (95% confidence interval, 10.6-72.7; P less than .001) and a significantly increased rate of progression of both plaque and intima-media thickness.

None of the investigators disclosed financial relationships related to these studies.

NEW YORK – While nowadays there is less likelihood that the hepatitis B virus causes rheumatic disease, major changes in epidemiology and drug therapy, especially the use of immunosuppressives, have made reactivation of the virus during the course of rheumatic disease treatment a major public health concern, according to Dr. Leonard H. Calabrese.

"HBV reactivation has been well known in cancer and transplantation but is now really coming to the fore in autoimmune and autoinflammatory diseases. It may be mild (asymptomatic viremia) or severe (fulminant liver failure and death) and has been observed in patients with both chronic infection or resolved disease. While it is largely preventable, unfortunately many physicians who regularly prescribe immunosuppressive therapies – including rheumatologists, oncologists, gastroenterologists, and dermatologists – do not recognize this potential," Dr. Calabrese said at a meeting sponsored by New York University.

The major risk of HBV is not during but after immunosuppression, when reactivation leading to severe or fatal hepatitis can occur. Reactivations have been reported rarely with low-dose prednisone and methotrexate, as well as all tumor necrosis factor (TNF) inhibitors, rituximab, abatacept, and infliximab, prompting a black box warning for many biologics, said Dr. Calabrese, director of the Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

In a retrospective study of 257 patients with positive HBV markers who were treated with TNF-targeted therapies, 39% with chronic infections (as indicated by the presence of HB surface antigens) developed HBV reactivation. Five developed acute liver failure, and four died (Medicine 2011;90:359-71). "This is not a trivial risk," Dr. Calabrese said.

Yet many rheumatologists do not screen for HBV prior to prescribing immunosuppressive therapy, he said. Dr. Calabrese cited a 2010 survey of rheumatologists that found that only 42% routinely screen for HBV before a patient begins nonbiologic disease-modifying antirheumatic drug therapy and 69% screen before prescribing a biologic DMARD. Seven percent of rheumatologists reported witnessing a reactivation event (Arthritis Care Res. 2010;62:704-11).

Of the three serologic markers for HBV (the hepatitis B surface antigen [HBsAg], the total hepatitis B core antibody [anti-HBc]), and the hepatitis B surface antibody (anti-HBsAb), Dr. Calabrese said he prefers HBsAg. "If you remember anything from this talk, remember that all patients with hepatitis B surface antigen need to be tended to before beginning any rheumatic therapy," he said. All positive tests should be followed up with HBV DNA testing.

Although all patients with a history of HBV are at some risk for HBV reactivation, with or without the presence of serologic markers, Dr. Calabrese outlined the relative risks of HBV reactivation as indicated by serologic findings. Those at highest risk are patients with chronic HBV infection (HBsAg positive, high level of HBV DNA), followed by inactive carriers (HBsAg positive, some HBV DNA) and those with resolved HBV (HBsAg negative, anti-HBc positive, anti-HBsAb positive). Those at lowest risk have resolved HBV (anti-HBc alone).

Rheumatologists should also be aware of the increased chance of HBV reactivation in high-risk populations. While in urban areas HBV is known to be associated with drug abuse, there is also a heightened risk in immigrants, especially those from Asia. Asian Americans are 2.7 times more likely to develop hepatocellular carcinoma. According to Dr. Calabrese, in mainland China there are an estimated 1 million people with rheumatologic problems who manifest chronic HBsAg positivity. "This is a global health problem," he noted.

Dr. Calabrese recommended that preemptive therapeutic measures be taken for all HBsAg-positive and HBV DNA–positive patients, including possible lifelong antiviral medication, and then these patients can be treated for their rheumatologic issues. Those who test positive for anti-HBc should be carefully monitored. "There should not be a patient with spondylitis, rheumatoid arthritis, lupus, or vasculitis who is getting less than effective therapy because they have chronic HBV," he said.

Dr. Calabrese reported no relevant financial disclosures.

rhnews@frontlinemedcom.com

NEW YORK – While nowadays there is less likelihood that the hepatitis B virus causes rheumatic disease, major changes in epidemiology and drug therapy, especially the use of immunosuppressives, have made reactivation of the virus during the course of rheumatic disease treatment a major public health concern, according to Dr. Leonard H. Calabrese.

"HBV reactivation has been well known in cancer and transplantation but is now really coming to the fore in autoimmune and autoinflammatory diseases. It may be mild (asymptomatic viremia) or severe (fulminant liver failure and death) and has been observed in patients with both chronic infection or resolved disease. While it is largely preventable, unfortunately many physicians who regularly prescribe immunosuppressive therapies – including rheumatologists, oncologists, gastroenterologists, and dermatologists – do not recognize this potential," Dr. Calabrese said at a meeting sponsored by New York University.

The major risk of HBV is not during but after immunosuppression, when reactivation leading to severe or fatal hepatitis can occur. Reactivations have been reported rarely with low-dose prednisone and methotrexate, as well as all tumor necrosis factor (TNF) inhibitors, rituximab, abatacept, and infliximab, prompting a black box warning for many biologics, said Dr. Calabrese, director of the Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

In a retrospective study of 257 patients with positive HBV markers who were treated with TNF-targeted therapies, 39% with chronic infections (as indicated by the presence of HB surface antigens) developed HBV reactivation. Five developed acute liver failure, and four died (Medicine 2011;90:359-71). "This is not a trivial risk," Dr. Calabrese said.

Yet many rheumatologists do not screen for HBV prior to prescribing immunosuppressive therapy, he said. Dr. Calabrese cited a 2010 survey of rheumatologists that found that only 42% routinely screen for HBV before a patient begins nonbiologic disease-modifying antirheumatic drug therapy and 69% screen before prescribing a biologic DMARD. Seven percent of rheumatologists reported witnessing a reactivation event (Arthritis Care Res. 2010;62:704-11).

Of the three serologic markers for HBV (the hepatitis B surface antigen [HBsAg], the total hepatitis B core antibody [anti-HBc]), and the hepatitis B surface antibody (anti-HBsAb), Dr. Calabrese said he prefers HBsAg. "If you remember anything from this talk, remember that all patients with hepatitis B surface antigen need to be tended to before beginning any rheumatic therapy," he said. All positive tests should be followed up with HBV DNA testing.

Although all patients with a history of HBV are at some risk for HBV reactivation, with or without the presence of serologic markers, Dr. Calabrese outlined the relative risks of HBV reactivation as indicated by serologic findings. Those at highest risk are patients with chronic HBV infection (HBsAg positive, high level of HBV DNA), followed by inactive carriers (HBsAg positive, some HBV DNA) and those with resolved HBV (HBsAg negative, anti-HBc positive, anti-HBsAb positive). Those at lowest risk have resolved HBV (anti-HBc alone).

Rheumatologists should also be aware of the increased chance of HBV reactivation in high-risk populations. While in urban areas HBV is known to be associated with drug abuse, there is also a heightened risk in immigrants, especially those from Asia. Asian Americans are 2.7 times more likely to develop hepatocellular carcinoma. According to Dr. Calabrese, in mainland China there are an estimated 1 million people with rheumatologic problems who manifest chronic HBsAg positivity. "This is a global health problem," he noted.

Dr. Calabrese recommended that preemptive therapeutic measures be taken for all HBsAg-positive and HBV DNA–positive patients, including possible lifelong antiviral medication, and then these patients can be treated for their rheumatologic issues. Those who test positive for anti-HBc should be carefully monitored. "There should not be a patient with spondylitis, rheumatoid arthritis, lupus, or vasculitis who is getting less than effective therapy because they have chronic HBV," he said.

Dr. Calabrese reported no relevant financial disclosures.

rhnews@frontlinemedcom.com

NEW YORK – While nowadays there is less likelihood that the hepatitis B virus causes rheumatic disease, major changes in epidemiology and drug therapy, especially the use of immunosuppressives, have made reactivation of the virus during the course of rheumatic disease treatment a major public health concern, according to Dr. Leonard H. Calabrese.

"HBV reactivation has been well known in cancer and transplantation but is now really coming to the fore in autoimmune and autoinflammatory diseases. It may be mild (asymptomatic viremia) or severe (fulminant liver failure and death) and has been observed in patients with both chronic infection or resolved disease. While it is largely preventable, unfortunately many physicians who regularly prescribe immunosuppressive therapies – including rheumatologists, oncologists, gastroenterologists, and dermatologists – do not recognize this potential," Dr. Calabrese said at a meeting sponsored by New York University.

The major risk of HBV is not during but after immunosuppression, when reactivation leading to severe or fatal hepatitis can occur. Reactivations have been reported rarely with low-dose prednisone and methotrexate, as well as all tumor necrosis factor (TNF) inhibitors, rituximab, abatacept, and infliximab, prompting a black box warning for many biologics, said Dr. Calabrese, director of the Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.

In a retrospective study of 257 patients with positive HBV markers who were treated with TNF-targeted therapies, 39% with chronic infections (as indicated by the presence of HB surface antigens) developed HBV reactivation. Five developed acute liver failure, and four died (Medicine 2011;90:359-71). "This is not a trivial risk," Dr. Calabrese said.

Yet many rheumatologists do not screen for HBV prior to prescribing immunosuppressive therapy, he said. Dr. Calabrese cited a 2010 survey of rheumatologists that found that only 42% routinely screen for HBV before a patient begins nonbiologic disease-modifying antirheumatic drug therapy and 69% screen before prescribing a biologic DMARD. Seven percent of rheumatologists reported witnessing a reactivation event (Arthritis Care Res. 2010;62:704-11).

Of the three serologic markers for HBV (the hepatitis B surface antigen [HBsAg], the total hepatitis B core antibody [anti-HBc]), and the hepatitis B surface antibody (anti-HBsAb), Dr. Calabrese said he prefers HBsAg. "If you remember anything from this talk, remember that all patients with hepatitis B surface antigen need to be tended to before beginning any rheumatic therapy," he said. All positive tests should be followed up with HBV DNA testing.

Although all patients with a history of HBV are at some risk for HBV reactivation, with or without the presence of serologic markers, Dr. Calabrese outlined the relative risks of HBV reactivation as indicated by serologic findings. Those at highest risk are patients with chronic HBV infection (HBsAg positive, high level of HBV DNA), followed by inactive carriers (HBsAg positive, some HBV DNA) and those with resolved HBV (HBsAg negative, anti-HBc positive, anti-HBsAb positive). Those at lowest risk have resolved HBV (anti-HBc alone).

Rheumatologists should also be aware of the increased chance of HBV reactivation in high-risk populations. While in urban areas HBV is known to be associated with drug abuse, there is also a heightened risk in immigrants, especially those from Asia. Asian Americans are 2.7 times more likely to develop hepatocellular carcinoma. According to Dr. Calabrese, in mainland China there are an estimated 1 million people with rheumatologic problems who manifest chronic HBsAg positivity. "This is a global health problem," he noted.

Dr. Calabrese recommended that preemptive therapeutic measures be taken for all HBsAg-positive and HBV DNA–positive patients, including possible lifelong antiviral medication, and then these patients can be treated for their rheumatologic issues. Those who test positive for anti-HBc should be carefully monitored. "There should not be a patient with spondylitis, rheumatoid arthritis, lupus, or vasculitis who is getting less than effective therapy because they have chronic HBV," he said.

Dr. Calabrese reported no relevant financial disclosures.

rhnews@frontlinemedcom.com

NEW YORK – Positive signs from the nearly completed first stage of a prospective prevention trial for cardiac neonatal lupus are giving investigators hope that hydroxychloroquine can reduce the risk of fetal heart block if given during pregnancy to women with systemic lupus erythematosus who have previously had a child with the condition.

The first stage of the PATCH (Preventive Approach to Congenital Heart Block With Hydroxychloroquine) study has enrolled all of its intended 19 pregnant women with systemic lupus erythematosus (SLE) and anti-SSA/Ro and anti-SSB/La antibodies who had a previous child with cardiac neonatal lupus (CNL). So far, cardiac abnormalities have been found in only 1 of 17 completed pregnancies in women who began taking 400-mg hydroxychloroquine (HCQ) before 10 weeks’ gestation. The study will go on to a second stage if fewer than three cases of second- or third-degree heart block occur. Enrollment of an additional 35 women is planned for the second stage, Dr. Jill P. Buyon said at the New York University Seminar in Advanced Rheumatology. She is director of the New York University Lupus Center, a professor in the division of rheumatology at New York University, and the principal investigator of the open-label PATCH study.

HCQ treatment will be considered efficacious if fewer than 6 mothers of the 54 total have a child with advanced congenital heart block. With this design, the study has 90% power to conclude that HCQ is preventive if the true recurrence rate with the treatment is 5%. In addition, the probability of rejecting the treatment for further study is 95% if the true recurrence rate is 18%, according to Dr. Buyon and her colleagues.

Women in the trial are given weekly serial fetal echocardiograms and blood tests for potential biomarkers of efficacy and compliance. The results of the study are expected to become an integral part of the counseling of women with anti-Ro/La antibodies who are considering pregnancy, according to the investigators.

"We need prophylactic treatment for autoimmune-associated congenital heart block because of the significant morbidity and mortality. The fibrosis is immutable, and there is no sustained reversal of complete heart block," Dr. Buyon said at the meeting sponsored by NYU. In previous work, Dr. Buyon reported a 17.5% mortality rate of neonates with cardiac neonatal lupus (CNL), 30% in utero (Circulation 2011;124:1927-35).

Congenital atrioventricular block and cardiomyopathy are the two major manifestations of CNL. The risk of CNL is approximately 2% in women with SLE who have given birth to an unaffected child, but the recurrence rate is 17.4% in those who have previously given birth to a baby with CNL. Mechanistically, HCQ’s inhibitory effect on toll-like receptors is thought to interfere with the pathophysiologic cascade underlying CNL.

Research leading up to the PATCH study indicated that HCQ might reduce the risk of CNL by 65% when pregnant mothers with SLE took HCQ throughout their pregnancy, Dr. Buyon said.

She and her colleagues analyzed a historical cohort gathered from three international databases (the Research Registry for Neonatal Lupus, the PRIDE study, and the PROMISSE study). In total, 257 pregnancies of anti-SSA/Ro–positive mothers with SLE who had previously given birth to a child with CNL were identified. Forty of the women were exposed throughout their pregnancies (starting before 10 weeks of gestation) to HCQ and 217 were not exposed to HCQ during pregnancy (Circulation 2012;126:76-82).

Significantly more fetuses in the unexposed group developed CNL (46 [21%] of 217) than in the exposed group (3 [8%] of 40 fetuses) (P = .05). The overall case fatality rate of the CNL fetuses in the unexposed group was 22%, compared with no deaths in the exposed group. No reduction in CNL recurrence was found for prednisone, dexamethasone, or fluorinated steroids.

Dr. Buyon reported having no relevant financial disclosures.

rhnews@frontlinemedcom.com

NEW YORK – Positive signs from the nearly completed first stage of a prospective prevention trial for cardiac neonatal lupus are giving investigators hope that hydroxychloroquine can reduce the risk of fetal heart block if given during pregnancy to women with systemic lupus erythematosus who have previously had a child with the condition.

The first stage of the PATCH (Preventive Approach to Congenital Heart Block With Hydroxychloroquine) study has enrolled all of its intended 19 pregnant women with systemic lupus erythematosus (SLE) and anti-SSA/Ro and anti-SSB/La antibodies who had a previous child with cardiac neonatal lupus (CNL). So far, cardiac abnormalities have been found in only 1 of 17 completed pregnancies in women who began taking 400-mg hydroxychloroquine (HCQ) before 10 weeks’ gestation. The study will go on to a second stage if fewer than three cases of second- or third-degree heart block occur. Enrollment of an additional 35 women is planned for the second stage, Dr. Jill P. Buyon said at the New York University Seminar in Advanced Rheumatology. She is director of the New York University Lupus Center, a professor in the division of rheumatology at New York University, and the principal investigator of the open-label PATCH study.

HCQ treatment will be considered efficacious if fewer than 6 mothers of the 54 total have a child with advanced congenital heart block. With this design, the study has 90% power to conclude that HCQ is preventive if the true recurrence rate with the treatment is 5%. In addition, the probability of rejecting the treatment for further study is 95% if the true recurrence rate is 18%, according to Dr. Buyon and her colleagues.

Women in the trial are given weekly serial fetal echocardiograms and blood tests for potential biomarkers of efficacy and compliance. The results of the study are expected to become an integral part of the counseling of women with anti-Ro/La antibodies who are considering pregnancy, according to the investigators.

"We need prophylactic treatment for autoimmune-associated congenital heart block because of the significant morbidity and mortality. The fibrosis is immutable, and there is no sustained reversal of complete heart block," Dr. Buyon said at the meeting sponsored by NYU. In previous work, Dr. Buyon reported a 17.5% mortality rate of neonates with cardiac neonatal lupus (CNL), 30% in utero (Circulation 2011;124:1927-35).

Congenital atrioventricular block and cardiomyopathy are the two major manifestations of CNL. The risk of CNL is approximately 2% in women with SLE who have given birth to an unaffected child, but the recurrence rate is 17.4% in those who have previously given birth to a baby with CNL. Mechanistically, HCQ’s inhibitory effect on toll-like receptors is thought to interfere with the pathophysiologic cascade underlying CNL.

Research leading up to the PATCH study indicated that HCQ might reduce the risk of CNL by 65% when pregnant mothers with SLE took HCQ throughout their pregnancy, Dr. Buyon said.

She and her colleagues analyzed a historical cohort gathered from three international databases (the Research Registry for Neonatal Lupus, the PRIDE study, and the PROMISSE study). In total, 257 pregnancies of anti-SSA/Ro–positive mothers with SLE who had previously given birth to a child with CNL were identified. Forty of the women were exposed throughout their pregnancies (starting before 10 weeks of gestation) to HCQ and 217 were not exposed to HCQ during pregnancy (Circulation 2012;126:76-82).

Significantly more fetuses in the unexposed group developed CNL (46 [21%] of 217) than in the exposed group (3 [8%] of 40 fetuses) (P = .05). The overall case fatality rate of the CNL fetuses in the unexposed group was 22%, compared with no deaths in the exposed group. No reduction in CNL recurrence was found for prednisone, dexamethasone, or fluorinated steroids.

Dr. Buyon reported having no relevant financial disclosures.

rhnews@frontlinemedcom.com

NEW YORK – Positive signs from the nearly completed first stage of a prospective prevention trial for cardiac neonatal lupus are giving investigators hope that hydroxychloroquine can reduce the risk of fetal heart block if given during pregnancy to women with systemic lupus erythematosus who have previously had a child with the condition.

The first stage of the PATCH (Preventive Approach to Congenital Heart Block With Hydroxychloroquine) study has enrolled all of its intended 19 pregnant women with systemic lupus erythematosus (SLE) and anti-SSA/Ro and anti-SSB/La antibodies who had a previous child with cardiac neonatal lupus (CNL). So far, cardiac abnormalities have been found in only 1 of 17 completed pregnancies in women who began taking 400-mg hydroxychloroquine (HCQ) before 10 weeks’ gestation. The study will go on to a second stage if fewer than three cases of second- or third-degree heart block occur. Enrollment of an additional 35 women is planned for the second stage, Dr. Jill P. Buyon said at the New York University Seminar in Advanced Rheumatology. She is director of the New York University Lupus Center, a professor in the division of rheumatology at New York University, and the principal investigator of the open-label PATCH study.

HCQ treatment will be considered efficacious if fewer than 6 mothers of the 54 total have a child with advanced congenital heart block. With this design, the study has 90% power to conclude that HCQ is preventive if the true recurrence rate with the treatment is 5%. In addition, the probability of rejecting the treatment for further study is 95% if the true recurrence rate is 18%, according to Dr. Buyon and her colleagues.

Women in the trial are given weekly serial fetal echocardiograms and blood tests for potential biomarkers of efficacy and compliance. The results of the study are expected to become an integral part of the counseling of women with anti-Ro/La antibodies who are considering pregnancy, according to the investigators.

"We need prophylactic treatment for autoimmune-associated congenital heart block because of the significant morbidity and mortality. The fibrosis is immutable, and there is no sustained reversal of complete heart block," Dr. Buyon said at the meeting sponsored by NYU. In previous work, Dr. Buyon reported a 17.5% mortality rate of neonates with cardiac neonatal lupus (CNL), 30% in utero (Circulation 2011;124:1927-35).

Congenital atrioventricular block and cardiomyopathy are the two major manifestations of CNL. The risk of CNL is approximately 2% in women with SLE who have given birth to an unaffected child, but the recurrence rate is 17.4% in those who have previously given birth to a baby with CNL. Mechanistically, HCQ’s inhibitory effect on toll-like receptors is thought to interfere with the pathophysiologic cascade underlying CNL.

Research leading up to the PATCH study indicated that HCQ might reduce the risk of CNL by 65% when pregnant mothers with SLE took HCQ throughout their pregnancy, Dr. Buyon said.

She and her colleagues analyzed a historical cohort gathered from three international databases (the Research Registry for Neonatal Lupus, the PRIDE study, and the PROMISSE study). In total, 257 pregnancies of anti-SSA/Ro–positive mothers with SLE who had previously given birth to a child with CNL were identified. Forty of the women were exposed throughout their pregnancies (starting before 10 weeks of gestation) to HCQ and 217 were not exposed to HCQ during pregnancy (Circulation 2012;126:76-82).

Significantly more fetuses in the unexposed group developed CNL (46 [21%] of 217) than in the exposed group (3 [8%] of 40 fetuses) (P = .05). The overall case fatality rate of the CNL fetuses in the unexposed group was 22%, compared with no deaths in the exposed group. No reduction in CNL recurrence was found for prednisone, dexamethasone, or fluorinated steroids.

Dr. Buyon reported having no relevant financial disclosures.

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